Patent Publication Number: US-2020292555-A1

Title: Cysteine reactive probes and uses thereof

Description:
CROSS-REFERENCE 
     This application is a continuation of U.S. application Ser. No. 15/331,745, filed on Oct. 21, 2016, which claims the benefit of U.S. Provisional Application No. 62/345,710, filed on Jun. 3, 2016, and U.S. Provisional Application No. 62/244,881, filed on Oct. 22, 2015, each of which are incorporated herein by reference in their entireties. 
    
    
     STATEMENT AS TO FEDERALLY SPONSORED RESEARCH 
     This invention was made with government support under grant numbers CA087660, GM090294, GM108208, and GM069832 awarded by the National Institutes of Health. Accordingly, the U.S. Government has certain rights in this invention. The government has certain rights in the invention. 
    
    
     SEQUENCE LISTING 
     The instant application contains a Sequence Listing which has been submitted electronically in ASCII format and is hereby incorporated by reference in its entirety. Said ASCII copy, created on Oct. 19, 2016, is named 48054-702_301_SL.txt and is 372,896 bytes in size. 
     BACKGROUND OF THE INVENTION 
     Protein function assignment has been benefited from genetic methods, such as target gene disruption, RNA interference, and genome editing technologies, which selectively disrupt the expression of proteins in native biological systems. Chemical probes offer a complementary way to perturb proteins that have the advantages of producing graded (dose-dependent) gain- (agonism) or loss- (antagonism) of-function effects that are introduced acutely and reversibly in cells and organisms. Small molecules present an alternative method to selectively modulate proteins and to serve as leads for the development of novel therapeutics. 
     SUMMARY OF THE INVENTION 
     Disclosed herein, in certain embodiments, is a method of identifying a cysteine containing protein as a binding target for a small molecule fragment, comprising: (a) obtaining a set of cysteine-reactive probe-protein complexes from a sample treated with a cysteine-reactive probe wherein the cysteine-reactive probe comprises a reactive moiety capable of forming a covalent bond with a cysteine residue located on the cysteine containing protein; (b) analyzing the set of cysteine-reactive probe-protein complexes by a proteomic analysis means; (c) based on step b), identifying a cysteine containing protein as the binding target for the small molecule fragment. In some embodiments, the method further comprises assigning a value to each of the cysteine containing protein from the set of cysteine-reactive probe-protein complexes for identifying a cysteine containing protein as the binding target for the small molecule fragment, wherein the value is determined based on the proteomic analysis means of step b) In some embodiments, the sample comprises a first cell solution and a second cell solution. In some embodiments, the method further comprises contacting the first cell solution with a small molecule fragment for an extended period of time prior to incubating the first cell solution with a first cysteine-reactive probe to generate a first group of cysteine-reactive probe-protein complexes. In some embodiments, the extended period of time is about 5, 10, 15, 20, 30, 60, 90, 120 minutes or longer. In some embodiments, the method further comprises contacting the second cell solution with a second cysteine-reactive probe to generate a second group of cysteine-reactive probe-protein complexes. In some embodiments, the first cysteine-reactive probe and the second cysteine-reactive probe are the same. In some embodiments, the first group and the second group of cysteine-reactive probe-protein complexes comprise the set of cysteine-reactive probe-protein complexes. In some embodiments, cells from the second cell solution are grown in a media (e.g., an isotopically enriched media). In some embodiments, cells from the first cell solution are grown in a media (e.g., an isotopically enriched media). In some embodiments, cells from both the first cell solution and the second cell solution are grown in two different isotopically enriched media so that cells from the first cell solution is distinguishable from cells obtained from the second cell solution. In other embodiments, cells from only one of the cell solutions (e.g., either the first cell solution or the second cell solution) are grown in an isotopically enriched media. In some embodiments, the method further comprises contacting the first cell solution with a first set of small molecule fragments and a complementing set of cysteine-reactive probes wherein each small molecule fragment competes with its complementing cysteine-reactive probe for binding with a cysteine residue, and wherein each small molecule fragment and each complementing cysteine-reactive probe are different within each respective set. In some embodiments, the method further comprises contacting the second cell solution with a second set of cysteine-reactive probes wherein the second set of cysteine-reactive probes is the same as the complementing set of cysteine-reactive probes, and wherein each cysteine-reactive probe is different within the set. In some embodiments, the first set of cysteine-reactive probes generates a third group of cysteine-reactive probe-protein complexes and the second set of cysteine-reactive probes generates a fourth group of cysteine-reactive probe-protein complexes. In some embodiments, the cysteine containing protein comprises a biologically active cysteine residue. In some embodiments, the biologically active cysteine site is a cysteine residue that is located about 10 Å or less to an active-site ligand or residue. In some embodiments, the cysteine residue that is located about 10 Å or less to the active-site ligand or residue is an active site cysteine. In some embodiments, the biologically active cysteine site is an active site cysteine. In some embodiments, the biologically active cysteine site is a cysteine residue that is located greater than 10 Å from an active-site ligand or residue. In some embodiments, the cysteine residue that is located greater than 10 Å from the active-site ligand or residue is a non-active site cysteine. In some embodiments, the biologically active cysteine site is a non-active site cysteine. In some embodiments, the small molecule fragment that covalently interacts with the biologically active cysteine impairs and/or inhibits activity of the cysteine containing protein. In some embodiments, the cysteine containing protein exists in an active form. In some embodiments, the small molecule fragment and/or the cysteine-reactive probe interact with the active form of the cysteine containing protein. In some embodiments, the cysteine containing protein exists in a pro-active form. In some embodiments, the small molecule fragment and/or the cysteine-reactive probe interact with the pro-active form of the cysteine containing protein. In some embodiments, the structural environment of the biologically active cysteine residue modulates the reactivity of the cysteine residue. In some embodiments, the structural environment is a hydrophobic environment or a hydrophilic environment. In some embodiments, the structural environment is a charged environment. In some embodiments, the structural environment is a nuclcophilic environment. In some embodiments, the cysteine containing protein is an enzyme, a transporter, a receptor, a channel protein, an adaptor protein, a chaperone, a signaling protein, a plasma protein, transcription related protein, translation related protein, mitochondrial protein, or cytoskeleton related protein. In some embodiments, the cysteine containing protein is an enzyme, a transporter, a receptor, a channel protein, an adaptor protein, a chaperone, a signaling protein, transcription related protein, or translation related protein. In some embodiments, the enzyme comprises kinases, proteases, or deubiquitinating enzymes. In some embodiments, the protease is a cysteine protease. In some embodiments, the cysteine protease comprises caspases. In some embodiments, the signaling protein comprises vascular endothelial growth factor. In some embodiments, the signaling protein comprises a redox signaling protein. In some embodiments, the cysteine containing protein is a protein illustrated in Table 1. In some embodiments, the cysteine containing protein is a protein illustrated in Table 2. In some embodiments, the cysteine containing protein is a protein illustrated in Table 3. In some embodiments, the cysteine containing protein comprises a cysteine residue denoted in Table 3. In some embodiments, the cysteine containing protein is a protein illustrated in Table 8. In some embodiments, the cysteine containing protein is a protein illustrated in Table 9. In some embodiments, the cysteine containing protein is a protein illustrated in Table 10A, Table 10B, Table 10C, Table 10D or Table 10E. In some embodiments, the small molecule fragment is a small molecule fragment of Formula (I): 
     
       
         
         
             
             
         
       
     
     wherein: RM is a reactive moiety selected from a Michael acceptor moiety, a leaving group moiety, or a moiety capable of forming a covalent bond with the thiol group of a cysteine residue; and F is a small molecule fragment moiety. In some embodiments, the Michael acceptor moiety comprises an alkene or an alkyne moiety. In some embodiments, F is obtained from a compound library. In some embodiments, the compound library comprises ChemBridge fragment library, Pyramid Platform Fragment-Based Drug Discovery, Maybridge fragment library, FRGx from AnalytiCon. TCI-Frag from AnCoreX, Bio Building Blocks from ASINEX, BioFocus 3D from Charles River, Fragments of Life (FOL) from Emerald Bio, Enamine Fragment Library, IOTA Diverse 1500, BIONET fragments library, Life Chemicals Fragments Collection, OTAVA fragment library. Prestwick fragment library, Selcia fragment library, TimTec fragment-based library. Allium from Vitas-M Laboratory, or Zenobia fragment library. In some embodiments, F is a small molecule fragment moiety illustrated in  FIG. 3 . In some embodiments, F further comprises a linker moiety that connects F to the carbonyl moiety. In some embodiments, the small molecule fragment is a small molecule fragment illustrated in  FIG. 3 . In some embodiments, the small molecule fragment is a specific inhibitor or a pan inhibitor. In some embodiments, the cysteine-reactive probe is a cysteine-reactive probe of Formula (II) 
     
       
         
         
             
             
         
       
     
     wherein: RM is a reactive moiety selected from a Michael acceptor moiety, a leaving group moiety, or a moiety capable of forming a covalent bond to the thiol group of a cysteine residue; and AHM is an affinity handle moiety. In some embodiments, the Michael acceptor moiety comprises an alkene or an alkyne moiety. In some embodiments, the affinity handle moiety comprises an affinity handle and a binding moiety that facilitates covalent interaction of the cysteine-reactive probe to a cysteine residue of a cysteine-containing protein. In some embodiments, the binding moiety is a small molecule fragment obtained from a compound library. In some embodiments, the compound library comprises ChemBridge fragment library, Pyramid Platform Fragment-Based Drug Discovery, Maybridge fragment library, FRGx from AnalytiCon, TCI-Frag from AnCoreX, Bio Building Blocks from ASINEX, BioFocus 3D from Charles River, Fragments of Life (FOL) from Emerald Bio, Enamine Fragment Library, IOTA Diverse 1500, BIONET fragments library, Life Chemicals Fragments Collection, OTAVA fragment library. Prestwick fragment library, Selcia fragment library, TimTec fragment-based library, Allium from Vitas-M Laboratory, or Zenobia fragment library. In some embodiments, the affinity handle is a bioorthogonal affinity handle. In some embodiments, the affinity handle comprises a carbodiimide, N-hydroxysuccinimide (NHS) ester, imidoester, pentafluorophenyl ester, hydroxymnethyl phosphine, maleimide, haloacetyl, pyridyl disulfide, thiosulfonate, vinylsulfone, hydrazide, alkoxyamine, alkyne, azide, or isocyanate group. In some embodiments, the affinity handle comprises an alkyne or an azide group. In some embodiments, the affinity handle is further conjugated to an affinity ligand. In some embodiments, the affinity ligand comprises a chromophore, a labeling group, or a combination thereof. In some embodiments, the chromophore comprises fluorochrome, non-fluorochrome chromophore, quencher, an absorption chromophore, fluorophore, organic dye, inorganic dye, metal chelate, or a fluorescent enzyme substrate. In some embodiments, the fluorophore comprises rhodamine, rhodol, fluorescein, thiofluorescein, aminofluorescein, carboxyfluorescein, chlorofluorescein, methylfluorescein, sulfofluorescein, aminorhodol, carboxyrhodol, chlororhodol, methylrhodol, sulforhodol, aminorhodamine, carboxyrhodamine, chlororhodamine, methylrhodamine, sulforhodamine, thiorhodamine, cyanine, indocarbocyanine, oxacarbocyanine, thiacarbocyanine, merocyanine, cyanine 2, cyanine 3, cyanine 3.5, cyanine 5, cyanine 5.5, cyanine 7, oxadiazole derivatives, pyridyloxazole, nitrobenzoxadiazole, benzoxadiazole, pyren derivatives, cascade blue, oxazine derivatives, Nile red, Nile blue, cresyl violet, oxazine 170, acridine derivatives, proflavin, acridine orange, acridine yellow, arylmethine derivatives, auramine, crystal violet, malachite green, tetrapyrrole derivatives, porphin, phtalocyanine, bilirubin 1-dimethylaminonaphthyl-5-sulfonate, 1-anilino-8-naphthalene sulfonate, 2-p-touidinyl-6-naphthalene sulfonate, 3-phenyl-7-isocyanatocoumarin, N-(p-(2-bcnzoxazolyl)phenyl)maleimide, stilbenes, pyrenes, 6-FAM (Fluorescein), 6-FAM (NHS Ester), 5(6)-FAM, 5-FAM, Fluorescein dT, 5-TAMRA-cadavarine, 2-aminoacridone, HEX, JOE (NHS Ester), MAX, TET, ROX, TAMRA, TARMA™ (NHS Ester), TEX 615, ATTO™ 488. ATTO™ 532, ATTO™ 550, ATTO™ 565, ATTO™ Rho101, ATTO™ 590. ATTO™ 633, ATTO™ 647N, TYE™ 563, TYE™ 665, or TYE™ 705. In some embodiments, the labeling group is biotin moiety, streptavidin moiety, bead, resin, a solid support, or a combination thereof. In some embodiments, the affinity handle moiety further comprises a chromophore. In some embodiments, the cysteine-reactive probe is a cysteine-reactive probe illustrated in  FIG. 3 . In some embodiments, the second cell solution further comprises a control. In some embodiments, the control is dimethyl sulfoxide (DMSO). In some embodiments, the protcomic analysis means comprises a mass spectroscopy method. In some embodiments, the mass spectroscopy method is a liquid-chromatography-mass spectrometry (LC-MS) method. In some embodiments, the method further comprises analyzing the results from the mass spectroscopy method by an algorithm for protein identification. In some embodiments, the algorithm combines the results from the mass spectroscopy method with a protein sequence database for protein identification. In some embodiments, the algorithm comprises ProLuCID algorithm, Probity, Scaffold, SEQUEST, or Mascot. In some embodiments, the mass spectroscopy method is a MALDI-TOF based method. In some embodiments, the value assigned to each of the cysteine containing protein is obtained from the mass spectroscopy analysis. In some embodiments, the value assigned to each of the cysteine containing protein is the area-under-the curve from a plot of signal intensity as a function of mass-to-charge ratio. In some embodiments, the identifying in step c) further comprises (i) locating a first value assigned to a cysteine containing protein from the first group of cysteine-reactive probe-protein complex and a second value of the same cysteine containing protein from the second group of cysteine-ractive probe-protein complex; and (ii) calculating a ratio between the two values assigned to the same cysteine containing protein. In some embodiments, the ratio of greater than 2 indicates that the cysteine containing protein is a candidate for interacting with the small molecule fragment. In some embodiments, the ratio of greater than 3 indicates that the cysteine containing protein is a candidate for interacting with the small molecule fragment. In some embodiments, the identifying in step c) further comprises calculating a percentage of inhibition of the cysteine-reactive probe to the cysteine containing protein. In some embodiments, the percentage of inhibition of greater than 50%, 60%, 70%, 80%, 90%, or at 100% indicates that the cysteine containing protein is a candidate for interacting with the small molecule fragment. In some embodiments, the cell is obtained from a tumor cell line. In some embodiments, the cell is obtained from a MDA-MB-231, Ramos, or Jurkat cell line. In some embodiments, the cell is obtained from a tumor sample. In some embodiments, the sample is a tissue sample. In some embodiments, the method is an in situ method. In some embodiments, the cysteine-reactive probe is not 4-hydroxynonenal or 15-deoxy-Δ12,14-prostaglandin J2. 
     Disclosed herein, in certain embodiments, is a method of screening a small molecule fragment for interaction with a cysteine containing protein, comprising: (a) harvesting a set of cysteine-reactive probe-protein complexes from a sample treated with a cysteine-reactive probe wherein the cysteine-reactive probe comprises a reactive moiety capable of forming a covalent bond with a cysteine residue located on the cysteine containing protein; (b) analyzing the set of cysteine-reactive probe-protein complexes by a proteomic analysis means; and (c) based on step b), identifying the small molecule fragment as interacting with the cysteine containing protein. In some embodiments, the method further comprises assigning a value to each of the cysteine containing protein from the set of cysteine-reactive probe-protein complexes prior to identifying the small molecule fragment as interacting with the cysteine containing protein, wherein the value is determined based on the proteomic analysis means of step b). In some embodiments, the sample comprises a first cell solution and a second cell solution. In some embodiments, the method further comprises contacting the first cell solution with a small molecule fragment for an extended period of time prior to incubating the first cell solution with a first cysteine-reactive probe to generate a first group of cysteine-reactive probe-protein complexes. In some embodiments, the extended period of time is about 5, 10, 15, 20, 30, 60, 90, 120 minutes or longer. In some embodiments, the method further comprises contacting the second cell solution with a second cysteine-reactive probe to generate a second group of cysteine-reactive probe-protein complexes. In some embodiments, the first cysteine-reactive probe and the second cysteine-reactive probe are the same. In some embodiments, the first group and the second group of cysteine-reactive probe-protein complexes comprise the set of cysteine-reactive probe-protein complexes. In some embodiments, cells from the second cell solution are grown in a media (e.g., an isotopically enriched media). In some embodiments, cells from the first cell solution are grown in a media (e.g., an isotopically enriched media). In some embodiments, cells from both the first cell solution and the second cell solution are grown in two different isotopically enriched media so that cells from the first cell solution is distinguishable from cells obtained from the second cell solution. In other embodiments, cells from only one of the cell solutions (e.g., either the first cell solution or the second cell solution) are grown in an isotopically enriched media. In some embodiments, the method further comprises contacting the first cell solution with a first set of small molecule fragments and a complementing set of cysteine-reactive probes wherein each small molecule fragment competes with its complementing cysteine-reactive probe for binding with a cysteine residue, and wherein each small molecule fragment and each complementing cysteine-reactive probe are different within each respective set. In some embodiments, the method further comprises contacting the second cell solution with a second set of cysteine-reactive probes wherein the second set of cysteine-reactive probes is the same as the complementing set of cysteine-reactive probes, and wherein each cysteine-reactive probe is different within the set. In some embodiments, the first set of cysteine-reactive probes generates a third group of cysteine-reactive probe-protein complexes and the second set of cysteine-reactive probes generates a fourth group of cysteine-reactive probe-protein complexes. In some embodiments, the cysteine containing protein comprises a biologically active cysteine residue. In some embodiments, the biologically active cysteine site is a cysteine residue that is located about 10 Å or less to an active-site ligand or residue. In some embodiments, the cysteine residue that is located about 10 Å or less to the active-site ligand or residue is an active site cysteine. In some embodiments, the biologically active cysteine site is an active site cysteine. In some embodiments, the biologically active cysteine site is a cysteine residue that is located greater than 10 Å from an active-site ligand or residue. In some embodiments, the cysteine residue that is located greater than 10 Å from the active-site ligand or residue is a non-active site cysteine. In some embodiments, the biologically active cysteine site is a non-active site cysteine. In some embodiments, the small molecule fragment that covalently interacts with the biologically active cysteine impairs and/or inhibits activity of the cysteine containing protein. In some embodiments, the cysteine containing protein exists in an active form. In some embodiments, the small molecule fragment and/or the cysteine-reactive probe interact with the active form of the cysteine containing protein. In some embodiments, the cysteine containing protein exists in a pro-active form. In some embodiments, the small molecule fragment and/or the cysteine-reactive probe interact with the pro-active form of the cysteine containing protein. In some embodiments, the structural environment of the biologically active cysteine residue modulates the reactivity of the cysteine residue. In some embodiments, the structural environment is a hydrophobic environment or a hydrophilic environment. In some embodiments, the structural environment is a charged environment. In some embodiments, the structural environment is a nucleophilic environment. In some embodiments, the cysteine containing protein is selected from an enzyme, a transporter, a receptor, a channel protein, an adaptor protein, a chaperone, a signaling protein, a plasma protein, transcription related protein, translation related protein, mitochondrial protein, or cytoskeleton related protein. In some embodiments, the cysteine containing protein is selected from an enzyme, a transporter, a receptor, a channel protein, an adaptor protein, a chaperone, a signaling protein, transcription related protein, or translation related protein. In some embodiments, the enzyme comprises kinases, proteases, or deubiquitinating enzymes. In some embodiments, the protease is a cysteine protease. In some embodiments, the cysteine protease comprises caspases. In some embodiments, the signaling protein comprises vascular endothelial growth factor. In some embodiments, the signaling protein comprises a redox signaling protein. In some embodiments, the cysteine containing protein is selected from Table 1. In some embodiments, the cysteine containing protein is a protein illustrated in Table 2. In some embodiments, the cysteine containing protein is a protein illustrated in Table 3. In some embodiments, the cysteine containing protein comprises a cysteine residue denoted in Table 3. In some embodiments, the cysteine containing protein is a protein illustrated in Table 8. In some embodiments, the cysteine containing protein is a protein illustrated in Table 9. In some embodiments, the cysteine containing protein is a protein illustrated in Table 10A, Table 10B, Table 10C, Table 10D or Table 10E. In some embodiments, the cysteine containing protein is TIGAR. IMPDH2, IDH1, IDH2, BTK, ZAK, TGM2, Map2k7, XPO1, Casp5, Casp8, ERCC3, Park 7 (Toxoplasma DJ-1), GSTO1, ALDH2, CTSZ, STAT1, STAT3, SMAD2, RBPJ, FOXK1, IRF4, IRF8, GTF3C1, or TCERG1. In some embodiments, the small molecule fragment is a small molecule fragment of Formula (I): 
     
       
         
         
             
             
         
       
     
     wherein: RM is a reactive moiety selected from a Michael acceptor moiety, a leaving group moiety, or a moiety capable of forming a covalent bond with the thiol group of a cysteine residue; and F is a small molecule fragment moiety. In some embodiments, the Michael acceptor moiety comprises an alkene or an alkyne moiety. In some embodiments, F is obtained from a compound library. In some embodiments, the compound library comprises ChemBridge fragment library, Pyramid Platform Fragment-Based Drug Discovery, Maybridge fragment library, FRGx from AnalytiCon, TCI-Frag from AnCoreX, Bio Building Blocks from ASINEX, BioFocus 3D from Charles River, Fragments of Life (FOL) from Emerald Bio, Enamine Fragment Library, IOTA Diverse 1500, BIONET fragments library, Life Chemicals Fragments Collection, OTAVA fragment library, Prestwick fragment library, Selcia fragment library, TimTec fragment-based library, Allium from Vitas-M Laboratory, or Zenobia fragment library. In some embodiments, F is a small molecule fragment moiety illustrated in  FIG. 3 . In some embodiments. F further comprises a linker moiety that connects F to the carbonyl moiety. In some embodiments, the small molecule fragment is a small molecule fragment illustrated in  FIG. 3 . In some embodiments, the small molecule fragment is a specific inhibitor or a pan inhibitor. In some embodiments, the cysteine-reactive probe is a cysteine-reactive probe of Formula (II): 
     
       
         
         
             
             
         
       
     
     wherein: RM is a reactive moiety selected from a Michael acceptor moiety, a leaving group moiety, or a moiety capable of forming a covalent bond to the thiol group of a cysteine residue; and AHM is an affinity handle moiety. In some embodiments, the Michael acceptor moiety comprises an alkene or an alkyne moiety. In some embodiments, the affinity handle moiety comprises an affinity handle and a binding moiety that facilitates covalent interaction of the cysteine-reactive probe to a cysteine residue of a cysteine-containing protein. In some embodiments, the binding moiety is a small molecule fragment obtained from a compound library. In some embodiments, the compound library comprises ChemBridge fragment library, Pyramid Platform Fragment-Based Drug Discovery, Maybridge fragment library, FRGx from AnalytiCon, TCI-Frag from AnCoreX, Bio Building Blocks from ASINEX, BioFocus 3D from Charles River. Fragments of Life (FOL) from Emerald Bio, Enamine Fragment Library, IOTA Diverse 1500, BIONET fragments library, Life Chemicals Fragments Collection, OTAVA fragment library, Prestwick fragment library, Selcia fragment library, TimTec fragment-based library, Allium from Vitas-M Laboratory, or Zenobia fragment library. In some embodiments, the affinity handle is a bioorthogonal affinity handle. In some embodiments, the affinity handle comprises a carbodiimide, N-hydroxysuccinimide (NHS) ester, imidoester, pentafluorophenyl ester, hydroxymethyl phosphine, maleimide, haloacetyl, pyridyl disulfide, thiosulfonate, vinylsulfone, hydrazide, alkoxyamine, alkyne, azide, or isocyanate group. In some embodiments, the affinity handle comprises an alkyne or an azide group. In some embodiments, the affinity handle is further conjugated to an affinity ligand. In some embodiments, the affinity ligand comprises a chromophore, a labeling group, or a combination thereof. In some embodiments, the chromophore comprises fluorochrome, non-fluorochrome chromophore, quencher, an absorption chromophore, fluorophore, organic dye, inorganic dye, metal chelate, or a fluorescent enzyme substrate. In some embodiments, the fluorophore comprises rhodamine, rhodol, fluorescein, thiofluorescein, aminofluorescein, carboxyfluorescein, chlorofluorescein, methylfluorescein, sulfofluorescein, aminorhodol, carboxyrhodol, chlororhodol, methylrhodol, sulforhodol, aminorhodamine, carboxyrhodamine, chlororhodamine, methylrhodamine, sulforhodamine, thiorhodamine, cyanine, indocarbocyanine, oxacarbocyanine, thiacarbocyanine, merocyanine, cyanine 2, cyanine 3, cyanine 3.5, cyanine 5, cyanine 5.5, cyanine 7, oxadiazole derivatives, pyridyloxazole, nitrobenzoxadiazole, benzoxadiazole, pyren derivatives, cascade blue, oxazine derivatives, Nile red, Nile blue, cresyl violet, oxazine 170, acridine derivatives, proflavin, acridine orange, acridine yellow, arylmethine derivatives, auramine, crystal violet, malachite green, tetrapyrrole derivatives, porphin, phtalocyanine, bilirubin 1-dimethylaminonaphthyl-5-sulfonate, 1-anilino-8-naphthalene sulfonate, 2-p-touidinyl-6-naphthalene sulfonate, 3-phenyl-7-isocyanatocoumarin, N-(p-(2-benzoxazolyl)phenyl)maleimide, stilbenes, pyrenes, 6-FAM (Fluorescein), 6-FAM (NHS Ester), 5(6)-FAM, 5-FAM, Fluorescein dT, 5-TAMRA-cadavarine, 2-aminoacridone, HEX, JOE (NHS Ester), MAX, TET, ROX, TAMRA, TARMA™ (NHS Ester), TEX 615, ATTO™ 488, ATTO™ 532, ATTO™550, ATTO™ 565, ATTO™ Rho101, ATTO™ 590, ATTO™ 633, ATTO™ 647N, TYE™ 563, TYE™ 665, or TYE™ 705. In some embodiments, the labeling group is biotin moiety, streptavidin moiety, bead, resin, a solid support, or a combination thereof. In some embodiments, the affinity handle moiety further comprises a chromophore. In some embodiments, the cysteine-reactive probe is a cysteine-reactive probe illustrated in  FIG. 3 . In some embodiments, the second cell solution further comprises a control. In some embodiments, the control is dimethyl sulfoxide (DMSO). In some embodiments, the proteomic analysis means comprises a mass spectroscopy method. In some embodiments, the mass spectroscopy method is a MALDI-TOF based method. In some embodiments, the mass spectroscopy method is a liquid-chromatography-mass spectrometry (LC-MS) method. In some embodiments, the method further comprises analyzing the results from the mass spectroscopy method by an algorithm for protein identification. In some embodiments, the algorithm combines the results from the mass spectroscopy method with a protein sequence database for protein identification. In some embodiments, the algorithm comprises ProLuCID algorithm, Probity, Scaffold, SEQUEST, or Mascot. In some embodiments, the value assigned to each of the cysteine containing protein is obtained from the mass spectroscopy analysis. In some embodiments, the value assigned to each of the cysteine containing protein is the area-under-the curve from a plot of signal intensity as a function of mass-to-charge ratio. In some embodiments, the identifying in step c) further comprises (i) locating a first value assigned to a cysteine containing protein from the first group of cysteine-reactive probe-protein complex and a second value of the same cysteine containing protein from the second group of cysteine-reactive probe-protein complex; and (ii) calculating a ratio between the two values assigned to the same cysteine containing protein. In some embodiments, the ratio of greater than 2 indicates that the cysteine containing protein is a candidate for interacting with the small molecule fragment. In some embodiments, the ratio of greater than 3 indicates that the cysteine containing protein is a candidate for interacting with the small molecule fragment. In some embodiments, the identifying in step c) further comprises calculating a percentage of inhibition of the cysteine-reactive probe to the cysteine containing protein. In some embodiments, the percentage of inhibition of greater than 50%, 60%, 70%, 80%, 90%, or at 100% indicates that the cysteine containing protein is a candidate for interacting with the small molecule fragment. In some embodiments, the cell is obtained from a tumor cell line. In some embodiments, the cell is obtained from a MDA-MB-231, Ramos, or Jurkat cell line. In some embodiments, the cell is obtained from a tumor sample. In some embodiments, the sample is a tissue sample. In some embodiments, the method is an in situ method. 
     Disclosed herein, in certain embodiments, is a method of mapping a biologically active cysteine site on a protein, comprising (a) harvesting a set of cysteine-reactive probe-protein complexes from a sample treated with a cysteine-reactive probe wherein the cysteine-reactive probe comprises a reactive moiety capable of forming a covalent bond with a cysteine residue located on the cysteine containing protein; (b) analyzing the set of cysteine-reactive probe-protein complexes by a proteomic analysis means; and (c) based on step b), mapping the biologically active cysteine site on the protein. In some embodiments, the sample comprises a first cell solution and a second cell solution. In some embodiments, the method further comprises contacting the first cell solution with a small molecule fragment for an extended period of time prior to incubating the first cell solution with a first cysteine-reactive probe to generate a first group of cysteine-reactive probe-protein complexes. In some embodiments, the extended period of time is about 5, 10, 15, 20, 30, 60, 90, 120 minutes or longer. In some embodiments, the method further comprises contacting the second cell solution with a second cysteine-reactive probe to generate a second group of cysteine-reactive probe-protein complexes. In some embodiments, the first cysteine-reactive probe and the second cysteine-reactive probe are the same. In some embodiments, the biologically active cysteine site is a cysteine residue that is located about 10 Å or less to an active-site ligand or residue. In some embodiments, the cysteine residue that is located about 10 Å or less to the active-site ligand or residue is an active site cysteine. In some embodiments, the biologically active cysteine site is an active site cysteine. In some embodiments, the biologically active cysteine site is a cysteine residue that is located greater than 10 Å from an active-site ligand or residue. In some embodiments, the cysteine residue that is located greater than 10 Å from the active-site ligand or residue is a non-active site cysteine. In some embodiments, the biologically active cysteine site is a non-active site cysteine. In some embodiments, the small molecule fragment that covalently interacts with the biologically active cysteine impairs and/or inhibits activity of the cysteine containing protein. In some embodiments, the cysteine containing protein exists in an active form. In some embodiments, the small molecule fragment and/or the cysteine-reactive probe interact with the active form of the cysteine containing protein. In some embodiments, the cysteine containing protein exists in a pro-active form. In some embodiments, the small molecule fragment and/or the cysteine-reactive probe interact with the pro-active form of the cysteine containing protein. In some embodiments, the structural environment of the biologically active cysteine residue modulates the reactivity of the cysteine residue. In some embodiments, the structural environment is a hydrophobic environment or a hydrophilic environment. In some embodiments, the structural environment is a charged environment. In some embodiments, the structural environment is a nucleophilic environment. In some embodiments, the protein is an enzyme, a transporter, a receptor, a channel protein, an adaptor protein, a chaperone, a signaling protein, a plasma protein, transcription related protein, translation related protein, mitochondrial protein, or cytoskeleton related protein. In some embodiments, the protein is an enzyme, a transporter, a receptor, a channel protein, an adaptor protein, a chaperone, a signaling protein, transcription related protein, or translation related protein. In some embodiments, the enzyme comprises kinases, proteases, or deubiquitinating enzymes. In some embodiments, the protease is a cysteine protease. In some embodiments, the cysteine protease comprises caspases. In some embodiments, the signaling protein comprises vascular endothelial growth factor. In some embodiments, the signaling protein comprises a redox signaling protein. In some embodiments, the protein is a protein illustrated in Table 1. In some embodiments, the cysteine containing protein is a protein illustrated in Table 2. In some embodiments, the cysteine containing protein is a protein illustrated in Table 3. In some embodiments, the cysteine containing protein comprises a cysteine residue denoted in Table 3. In some embodiments, the cysteine containing protein is a protein illustrated in Table 8. In some embodiments, the cysteine containing protein is a protein illustrated in Table 9. In some embodiments, the cysteine containing protein is a protein illustrated in Table 10A. Table 10B. Table 10C, Table 10D or Table 10E. In some embodiments, the small molecule fragment is a small molecule fragment of Formula (I): 
     
       
         
         
             
             
         
       
     
     wherein: RM is a reactive moiety selected from a Michael acceptor moiety, a leaving group moiety, or a moiety capable of forming a covalent bond with the thiol group of a cysteine residue, and F is a small molecule fragment moiety. In some embodiments, the Michael acceptor moiety comprises an alkene or an alkyne moiety. In some embodiments, F is obtained from a compound library. In some embodiments, the compound library comprises ChemBridge fragment library, Pyramid Platform Fragment-Based Drug Discovery, Maybridge fragment library, FRGx from AnalytiCon, TCI-Frag from AnCoreX, Bio Building Blocks from ASINEX, BioFocus 3D from Charles River. Fragments of Life (FOL) from Emerald Bio, Enamine Fragment Library, IOTA Diverse 1500, BIONET fragments library, Life Chemicals Fragments Collection, OTAVA fragment library, Prestwick fragment library, Selcia fragment library, TimTec fragment-based library, Allium from Vitas-M Laboratory. or Zenobia fragment library. In some embodiments, F is a small molecule fragment moiety illustrated in  FIG. 3 . In some embodiments. F further comprises a linker moiety that connects F to the carbonyl moiety. In some embodiments, the small molecule fragment is a small molecule fragment illustrated in  FIG. 3 . In some embodiments, the small molecule fragment is a specific inhibitor or a pan inhibitor. In some embodiments, the cysteine-reactive probe is a cysteine-reactive probe of Formula (II): 
     
       
         
         
             
             
         
       
     
     wherein: RM is a reactive moiety selected from a Michael acceptor moiety, a leaving group moiety, or a moiety capable of forming a covalent bond to the thiol group of a cysteine residue; and AHM is an affinity handle moiety. In some embodiments, the Michael acceptor moiety comprises an alkene or an alkyne moiety. In some embodiments, the affinity handle moiety comprises an affinity handle and a binding moiety that facilitates covalent interaction of the cysteine-reactive probe to a cysteine residue of a cysteine-containing protein. In some embodiments, the binding moiety is a small molecule fragment obtained from a compound library. In some embodiments, the compound library comprises ChemBridge fragment library, Pyramid Platform Fragment-Based Drug Discovery, Maybridge fragment library, FRGx from AnalytiCon. TCI-Frag from AnCoreX, Bio Building Blocks from ASINEX, BioFocus 3D from Charles River. Fragments of Life (FOL) from Emerald Bio, Enamine Fragment Library, IOTA Diverse 1500, BIONET fragments library, Life Chemicals Fragments Collection, OTAVA fragment library, Prestwick fragment library, Selcia fragment library, TimTec fragment-based library, Allium from Vitas-M Laboratory, or Zenobia fragment library. In some embodiments, the affinity handle is a bioorthogonal affinity handle. In some embodiments, the affinity handle comprises a carbodiimide, N-hydroxysuccinimide (NHS) ester, imidoester, pentafluorophenyl ester, hydroxymethyl phosphine, maleimide, haloacetyl, pyridyl disulfide, thiosulfonate, vinylsulfone, hydrazide, alkoxyamine, alkyne, azide, or isocyanate group. In some embodiments, the affinity handle comprises an alkyne or an azide group. In some embodiments, the affinity handle is further conjugated to an affinity ligand. In some embodiments, the affinity ligand comprises a chromophore, a labeling group, or a combination thereof. In some embodiments, the chromophore comprises fluorochrome, non-fluorochrome chromophore, quencher, an absorption chromophore, fluorophore, organic dye, inorganic dye, metal chelate, or a fluorescent enzyme substrate. In some embodiments, the fluorophore comprises rhodamine, rhodol, fluorescein, thiofluorescein, aminofluorescein, carboxyfluorescein, chlorofluorescein, methylfluorescein, sulfofluorescein, aminorhodol, carboxyrhodol, chlororhodol, methylrhodol, sulforhodol, aminorhodamine, carboxyrhodamine, chlororhodamine, methylrhodamine, sulforhodamine, thiorhodamine, cyanine, indocarbocyanine, oxacarbocyanine, thiacarbocyanine, merocyanine, cyanine 2, cyanine 3, cyanine 3.5, cyanine 5, cyanine 5.5, cvanine 7, oxadiazole derivatives, pyridyloxazole, nitrobenzoxadiazole, benzoxadiazole, pyren derivatives, cascade blue, oxazine derivatives, Nile red, Nile blue, cresyl violet, oxazine 170, acridine derivatives, proflavin, acridine orange, acridine yellow, arylmethine derivatives, auramine, crystal violet, malachite green, tetrapyrrole derivatives, porphin, phtalocyanine, bilirubin 1-dimethylaminonaphthyl-5-sulfonate, 1-anilino-8-naphthalene sulfonate, 2-p-touidinyl-6-naphthalene sulfonate, 3-phenyl-7-isocyanatocoumarin, N-(p-(2-benzoxazolyl)phenyl)maleimide, stilbenes, pyrenes, 6-FAM (Fluorescein), 6-FAM (NHS Ester), 5(6)-FAM, 5-FAM, Fluorescein dT, 5-TAMRA-cadavarine, 2-aminoacridone, HEX, JOE (NHS Ester), MAX, TET, ROX, TAMRA, TARMA™ (NHS Ester), TEX 615, ATTO™ 488, ATTO™ 532, ATTO™ 550, ATTO™ 565, ATTO™ Rho101 ATTO™ 590, ATTO™ 633, ATTO™ 647N, TYE™ 563, TYE™ 665, or TYE™ 705. In some embodiments, the labeling group is biotin moiety, streptavidin moiety, bead, resin, a solid support, or a combination thereof. In some embodiments, the affinity handle moiety further comprises a chromophore. In some embodiments, the cysteine-reactive probe is a cysteine-reactive probe illustrated in  FIG. 3 . In some embodiments, the second cell solution further comprises a control. In some embodiments, the control is dimethyl sulfoxide (DMSO). In some embodiments, the proteomic analysis means comprises a mass spectroscopy method. In some embodiments, the mass spectroscopy method is a liquid-chromatography-mass spectrometry (LC-MS) method. In some embodiments, the method further comprises analyzing the results from the mass spectroscopy method by an algorithm for protein identification. In some embodiments, the algorithm combines the results from the mass spectroscopy method with a protein sequence database for protein identification. In some embodiments, the algorithm comprises ProLuCID algorithm, Probity, Scaffold, SEQUEST, or Mascot. In some embodiments, the mass spectroscopy method is a MALDI-TOF based method. In some embodiments, the cell is obtained from a tumor cell line. In some embodiments, the cell is obtained from a MDA-MB-231, Ramos, or Jurkat cell line. In some embodiments, the cell is obtained from a tumor sample. In some embodiments, the sample is a tissue sample. In some embodiments, the method is an in situ method. 
     Disclosed herein, in certain embodiments, is a composition comprising: a small molecule fragment of Formula (I): 
     
       
         
         
             
             
         
       
     
     wherein: RM is a reactive moiety selected from a Michael acceptor moiety, a leaving group moiety, or a moiety capable of forming a covalent bond with the thiol group of a cysteine residue; and F is a small molecule fragment moiety; and a cysteine containing protein wherein the cysteine containing protein is covalently bond to the small molecule fragment. In some embodiments, the Michael acceptor moiety comprises an alkene or an alkyne moiety. In some embodiments, F is obtained from a compound library. In some embodiments, F is a small molecule fragment moiety illustrated in  FIG. 3 . In some embodiments, F further comprises a linker moiety that connects F to the carbonyl moiety. 
     Disclosed herein, in certain embodiments, is a composition comprising: a cysteine-reactive probe of Formula (II): 
     
       
         
         
             
             
         
       
     
     wherein: RM is a reactive moiety selected from a Michael acceptor moiety, a leaving group moiety, or a moiety capable of forming a covalent bond to the thiol group of a cysteine residue; and AHM is an affinity handle moiety; and a cysteine containing protein wherein the cysteine containing protein is covalently bond to the cysteine-reactive probe. In some embodiments, the Michael acceptor moiety comprises an alkene or an alkyne moiety. In some embodiments, the affinity handle moiety comprises an affinity handle and a binding moiety that facilitates covalent interaction of the cysteine-reactive probe to a cysteine residue of a cysteine-containing protein. In some embodiments, the binding moiety is a small molecule fragment obtained from a compound library. In some embodiments, the affinity handle is a bioorthogonal affinity handle. In some embodiments, the affinity handle comprises a carbodiimide, N-hydroxysuccinimide (NHS) ester, imidoester, pentafluorophenyl ester, hydroxymethyl phosphine, maleimide, haloacetyl, pyridyl disulfide, thiosulfonate, vinylsulfone, hydrazide, alkoxyamine, alkyne, azide, or isocyanate group. In some embodiments, the affinity handle is further conjugated to an affinity ligand. In some embodiments, the affinity handle moiety further comprises a chromophore. In some embodiments, the cysteine-reactive probe is a cysteine-reactive probe illustrated in  FIG. 3 . 
     Disclosed herein, in certain embodiments, is a composition comprising: an isolated sample wherein the isolated sample is an isolated cell or a tissue sample; and a cysteine-reactive probe to be assayed for its ability to interact with a cysteine containing protein expressed in the isolated sample. In some embodiments, the composition further comprises contacting the isolated sample with a small molecule fragment for an extended period of time prior to incubating the isolated sample with the cysteine-reactive probe to generate a cysteine-reactive probe-protein complex. In some embodiments, the extended period of time is about 5, 10, 15, 20, 30, 60, 90, 120 minutes or longer. 
     Disclosed herein, in certain embodiments, is an isolated treated cell comprising a cysteine-reactive probe covalently attached to a cysteine containing protein. In some embodiments, the isolated treated cell further comprises a set of cysteine-reactive probes wherein each of the cysteine-reactive probes is covalently attached to a cysteine containing protein. 
     Disclosed herein, in certain embodiments, is an isolated treated cell comprising a small molecule fragment covalently attached to a cysteine containing protein. In some embodiments, the isolated treated cell further comprises a set of small molecule fragments wherein each of the small molecule fragments is covalently attached to a cysteine containing protein. In some embodiments, the isolated treated cell further comprises a cysteine-reactive probe. In some embodiments, the isolated treated cell further comprises a set of cysteine-reactive probes. 
     Disclosed herein, in certain embodiments, is an isolated treated population of cells comprising a set of cysteine-reactive probes covalently attached to cysteine containing proteins. Also disclosed herein, in certain embodiments, is an isolated treated population of cells comprising a set of small molecule fragments covalently attached to cysteine containing proteins. In some embodiments, the isolated treated population of cells further comprises a set of cysteine-reactive probes. 
     Disclosed herein, in certain embodiments, is an isolated and purified polypeptide comprising at least 90% sequence identity to at least seven contiguous amino acids of an amino acid sequence selected from Tables 1-3 or 8-9. In some embodiments, the isolated and purified polypeptide comprising at least 95% sequence identity to at least seven contiguous amino acids of an amino acid sequence selected from Tables 1-3 or 8-9. In some embodiments, the isolated and purified polypeptide comprising 100% sequence identity to at least seven contiguous amino acids of an amino acid sequence selected from Tables 1-3 or 8-9. In some embodiments, the isolated and purified polypeptide consisting 100% sequence identity to the full length of an amino acid sequence selected from Tables 1-3 or 8-9. In some embodiments, the isolated and purified polypeptide is at most 50 amino acids in length. A polypeptide probe for screening a small molecule fragment comprising an isolated and purified polypeptide described herein. 
     Further disclosed herein, in certain embodiments, is a nucleic acid encoding a polypeptide comprising at least 90% sequence identity at least seven contiguous amino acids of an amino acid sequence selected from Tables 1-3 or 8-9. In some embodiments, the nucleic acid encoding a polypeptide comprising at least 95% sequence identity at least seven contiguous amino acids of an amino acid sequence selected from Tables 1-3 or 8-9. In some embodiments, the nucleic acid encoding a polypeptide comprising 100% sequence identity at least seven contiguous amino acids of an amino acid sequence selected from Tables 1-3 or 8-9. In some embodiments, the nucleic acid encoding a polypeptide consisting 100% sequence identity to the full length of an amino acid sequence selected from Tables 1-3 or 8-9. 
     Disclosed herein, in certain embodiments, is a modified cysteine containing protein comprising a small molecule fragment having a covalent bond to a cysteine residue of a cysteine containing protein, wherein the small molecule fragment is a small molecule fragment of Formula (I): 
     
       
         
         
             
             
         
       
     
     wherein: RM is a reactive moiety selected from a Michael acceptor moiety, a leaving group moiety, or a moiety capable of forming a covalent bond with the thiol group of a cysteine residue; and F is a small molecule fragment moiety. In some embodiments, the cysteine containing protein is a protein illustrated in Table 1. In some embodiments, the cysteine containing protein is a protein illustrated in Table 2. In some embodiments, the cysteine containing protein is a protein illustrated in Table 3. In some embodiments, the cysteine containing protein comprises a cysteine residue denoted in Table 3. In some embodiments, the cysteine containing protein is a protein illustrated in Table 8. In some embodiments, the cysteine containing protein is a protein illustrated in Table 9. In some embodiments, the Michael acceptor moiety comprises an alkene or an alkyne moiety. In some embodiments, F is obtained from a compound library. In some embodiments, F is a small molecule fragment moiety illustrated in  FIG. 3 . In some embodiments, F further comprises a linker moiety that connects F to the carbonyl moiety. In some embodiments, the small molecule fragment binds irreversibly to the cysteine containing protein. In some embodiments, the small molecule fragment binds reversibly to the cysteine containing protein. 
     Disclosed herein, in certain embodiments, is a modified cysteine containing protein comprising a small molecule fragment having a covalent bond to a cysteine residue of a cysteine containing protein, wherein the small molecule fragment has a molecular weight of about 150 Dalton or higher. In some embodiments, the small molecule fragment has a molecular weight of about 175, 200, 225, 250, 275, 300, 350, 400, 450, 500, 550, 600, 650, 700, 750, 800, 850, 900, 950, 1000 Dalton, or higher. In some embodiments, the molecular weight of the small molecule fragment is prior to enrichment with a halogen, a nonmetal, or a transition metal. In some embodiments, the molecular weight of the small molecule fragment is calculated based on carbon and hydrogen atoms and optionally further based on nitrogen, oxygen and/or sulfur atoms. In some embodiments, the molecular weight of the small molecule fragment does not include the molecular weight of a halogen, a transition metal or a combination thereof. In some embodiments, the cysteine containing protein is about 20, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 150, 200, 250, 300, 350, 400, 450, 500, 600, 700, 800, 900, 1000 amino acid residues in length or more. In some embodiments, the cysteine containing protein is a protein illustrated in Table 1. In some embodiments, the cysteine containing protein is a protein illustrated in Table 2. In some embodiments, the cysteine containing protein is a protein illustrated in Table 3. In some embodiments, the cysteine containing protein comprises a cysteine residue denoted in Table 3. In some embodiments, the cysteine containing protein is a protein illustrated in Table 8. In some embodiments, the cysteine containing protein is a protein illustrated in Table 9. In some embodiments, the small molecule fragment is a small molecule fragment of Formula (I): 
     
       
         
         
             
             
         
       
     
     wherein: RM is a reactive moiety selected from a Michael acceptor moiety, a leaving group moiety, or a moiety capable of forming a covalent bond with the thiol group of a cysteine residue; and F is a small molecule fragment moiety. In some embodiments, the small molecule fragment of Formula (I) has a molecular weight of about 150, 175, 200, 225, 250, 275, 300, 350, 400, 450, 500, 550, 600, 650, 700, 750, 800, 850, 900, 950, 1000 Dalton, or higher. In some embodiments, the Michael acceptor moiety comprises an alkene or an alkyne moiety. In some embodiments, F is obtained from a compound library. In some embodiments, F is a small molecule fragment moiety illustrated in  FIG. 3 . In some embodiments, F further comprises a linker moiety that connects F to the carbonyl moiety. In some embodiments, the small molecule fragment bond irreversibly to the cysteine containing protein. In some embodiments, the small molecule fragment bond reversibly to the cysteine containing protein. 
     Disclosed herein, in certain embodiments, is a cysteine containing protein-small molecule fragment complex produced by a process comprising contacting a cell solution with a small molecule fragment of Formula (I): 
     
       
         
         
             
             
         
       
     
     wherein: RM is a reactive moiety selected from a Michael acceptor moiety, a leaving group moiety, or a moiety capable of forming a covalent bond with the thiol group of a cysteine residue, and F is a small molecule fragment moiety; and wherein the contacting time is between about 5 minutes and about 2 hours. In some embodiments, the Michael acceptor moiety comprises an alkene or an alkyne moiety. In some embodiments, F is obtained from a compound library. In some embodiments, F is a small molecule fragment moiety illustrated in  FIG. 3 . In some embodiments, F further comprises a linker moiety that connects F to the carbonyl moiety. In some embodiments, the small molecule fragment of Formula (I) has a molecular weight of about 150, 175, 200, 225, 250, 275, 300, 350, 400, 450, 500, 550, 600, 650, 700, 750, 800, 850, 900, 950, 1000 Dalton, or higher. In some embodiments, the cysteine containing protein is a protein illustrated in Table 1. In some embodiments, the cysteine containing protein is a protein illustrated in Table 2. In some embodiments, the cysteine containing protein is a protein illustrated in Table 3. In some embodiments, the cysteine containing protein comprises a cysteine residue denoted in Table 3. In some embodiments, the cysteine containing protein is a protein illustrated in Table 8. In some embodiments, the cysteine containing protein is a protein illustrated in Table 9. In some embodiments, the cysteine containing protein is a protein illustrated in Table 10A, Table 10B, Table 10C, Table 10D or Table 10E. In some embodiments, the small molecule fragment binds irreversibly to the cysteine containing protein. In some embodiments, the small molecule fragment binds reversibly to the cysteine containing protein. 
     Disclosed herein, in certain embodiments, is a modified cysteine containing protein comprising a cysteine-reactive probe having a covalent bond to a cysteine residue of a cysteine containing protein, wherein the cysteine-reactive probe is a cysteine-reactive probe of Formula (II): 
     
       
         
         
             
             
         
       
     
     wherein: RM is a reactive moiety selected from a Michael acceptor moiety, a leaving group moiety, or a moiety capable of forming a covalent bond to the thiol group of a cysteine residue; and AHM is an affinity handle moiety. In some embodiments, the cysteine containing protein is a protein illustrated in Table 1. In some embodiments, the cysteine containing protein is a protein illustrated in Table 2. In some embodiments, the cysteine containing protein is a protein illustrated in Table 8. In some embodiments, the cysteine containing protein is a protein illustrated in Table 9. In some embodiments, the cysteine containing protein is a protein illustrated in Table 10A, Table 10B, Table 10C, Table 10D or Table 10E. In some embodiments, the Michael acceptor moiety comprises an alkene or an alkyne moiety. In some embodiments, the affinity handle moiety comprises an affinity handle and a binding moiety that facilitates covalent interaction of the cysteine-reactive probe to a cysteine residue of a cysteine-containing protein. In some embodiments, the binding moiety is a small molecule fragment obtained from a compound library. In some embodiments, the affinity handle is a bioorthogonal affinity handle. In some embodiments, the affinity handle comprises a carbodiimide, N-hydroxysuccinimide (NHS) ester, imidoester, pentafluorophenyl ester, hydroxymethyl phosphine, maleimide, haloacetyl, pyridyl disulfide, thiosulfonate, vinylsulfone, hydrazide, alkoxyamine, alkyne, azide, or isocyanate group. In some embodiments, the affinity handle is further conjugated to an affinity ligand. In some embodiments, the affinity handle moiety further comprises a chromophore. In some embodiments, the cysteine-reactive probe is a cysteine-reactive probe illustrated in  FIG. 3 . In some embodiments, the cysteine-reactive probe binds irreversibly to the cysteine containing protein. In some embodiments, the cysteine-reactive probe binds reversibly to the cysteine containing protein. 
     Disclosed herein, in certain embodiments, is a cysteine-reactive probe of Formula (II): 
     
       
         
         
             
             
         
       
     
     wherein: RM is a reactive moiety selected from a Michael acceptor moiety, a leaving group moiety, or a moiety capable of forming a covalent bond to the thiol group of a cysteine residue, and AHM is an affinity handle moiety. In some embodiments, the cysteine-reactive probe covalently binds to a cysteine residue on a cysteine containing protein. In some embodiments, cysteine containing protein is a protein illustrated in Table 1. In some embodiments, the cysteine containing protein is a protein illustrated in Table 2. In some embodiments, the cysteine containing protein is a protein illustrated in Table 3. In some embodiments, the cysteine containing protein comprises a cysteine residue denoted in Table 3. In some embodiments, the cysteine containing protein is a protein illustrated in Table 8. In some embodiments, the cysteine containing protein is a protein illustrated in Table 9. In some embodiments, the cysteine containing protein is a protein illustrated in Table 10A, Table 10B, Table 10C, Table 10D or Table 10E. In some embodiments, the cysteine-reactive probe binds irreversibly to the cysteine containing protein. In some embodiments, the cysteine-reactive probe binds reversibly to the cysteine containing protein. 
     Disclosed herein, in certain embodiments, is a compound capable of covalently binding to a cysteine containing protein identified, using the method comprising: (a) obtaining a set of cysteine-reactive probe-protein complexes from a sample wherein the cysteine-reactive probe comprises a reactive moiety capable of forming a covalent bond with a cysteine residue located on the cysteine containing protein; (b) analyzing the set of cysteine-reactive probe-protein complexes by a proteomic analysis means; (c) based on step b), identifying a cysteine containing protein as the binding target for the compound. In some embodiments, the compound is a small molecule fragment. In some embodiments, the small molecule fragment is a small molecule fragment of Formula (I): 
     
       
         
         
             
             
         
       
     
     wherein: RM is a reactive moiety selected from a Michael acceptor moiety, a leaving group moiety, or a moiety capable of forming a covalent bond with the thiol group of a cysteine residue; and F is a small molecule fragment moiety. In some embodiments, the Michael acceptor moiety comprises an alkene or an alkyne moiety. In some embodiments, F is obtained from a compound library. In some embodiments, the compound library comprises ChemBridge fragment library, Pyramid Platform Fragment-Based Drug Discovery, Maybridge fragment library, FRGx from AnalytiCon, TCI-Frag from AnCoreX, Bio Building Blocks from ASINEX, BioFocus 3D from Charles River, Fragments of Life (FOL) from Emerald Bio, Enamine Fragment Library, IOTA Diverse 1500, BIONET fragments library, Life Chemicals Fragments Collection, OTAVA fragment library, Prestwick fragment library, Selcia fragment library, TimTec fragment-based library, Allium from Vitas-M Laboratory. or Zenobia fragment library. In some embodiments, F is a small molecule fragment moiety illustrated in  FIG. 3 . In some embodiments, F further comprises a linker moiety that connects F to the carbonyl moiety. In some embodiments, the small molecule fragment is a small molecule fragment illustrated in  FIG. 3 . In some embodiments, the small molecule fragment is a specific inhibitor or a pan inhibitor. In some embodiments, the cysteine containing protein comprises a biologically active cysteine residue. In some embodiments, the biologically active cysteine site is a cysteine residue that is located about 10 Å or less to an active-site ligand or residue. In some embodiments, the cysteine residue that is located about 10 Å or less to the active-site ligand or residue is an active site cysteine. In some embodiments, the biologically active cysteine site is an active site cysteine. In some embodiments, the biologically active cysteine site is a cysteine residue that is located greater than 10 Å from an active-site ligand or residue. In some embodiments, the cysteine residue that is located greater than 10 Å from the active-site ligand or residue is a non-active site cysteine. In some embodiments, the biologically active cysteine site is a non-active site cysteine. In some embodiments, the small molecule fragment that covalently interacts with the biologically active cysteine impairs and/or inhibits activity of the cysteine containing protein. In some embodiments, the cysteine containing protein exists in an active form. In some embodiments, the small molecule fragment and/or the cysteine-reactive probe interact with the active form of the cysteine containing protein. In some embodiments, the cysteine containing protein exists in a pro-active form. In some embodiments, the small molecule fragment and/or the cysteine-reactive probe interact with the pro-active form of the cysteine containing protein. In some embodiments, the structural environment of the biologically active cysteine residue modulates the reactivity of the cysteine residue. In some embodiments, the structural environment is a hydrophobic environment or a hydrophilic environment. In some embodiments, the structural environment is a charged environment. In some embodiments, the structural environment is a nucleophilic environment. In some embodiments, the cysteine containing protein is an enzyme, a transporter, a receptor, a channel protein, an adaptor protein, a chaperone, a signaling protein, a plasma protein, transcription related protein, translation related protein, mitochondrial protein, or cytoskeleton related protein. In some embodiments, the cysteine containing protein is an enzyme, a transporter, a receptor, a channel protein, an adaptor protein, a chaperone, a signaling protein, transcription related protein, or translation related protein. In some embodiments, the enzyme comprises kinases, proteases, or deubiquitinating enzymes. In some embodiments, the protease is a cysteine protease. In some embodiments, the cysteine protease comprises caspases. In some embodiments, the signaling protein comprises vascular endothelial growth factor. In some embodiments, the signaling protein comprises a redox signaling protein. In some embodiments, the cysteine containing protein is a protein illustrated in Table 1. In some embodiments, the cysteine containing protein is a protein illustrated in Table 2. In some embodiments, the cysteine containing protein is a protein illustrated in Table 3. In some embodiments, the cysteine containing protein comprises a cysteine residue denoted in Table 3. In some embodiments, the cysteine containing protein is a protein illustrated in Table 8. In some embodiments, the cysteine containing protein is a protein illustrated in Table 9. In some embodiments, the cysteine containing protein is a protein illustrated in Table 10A. Table 10B, Table 10C, Table 10D or Table 10E. 
     Disclosed herein, in certain embodiments, is a derivative of a cysteine-containing protein having the structure of Formula (I), 
     
       
         
         
             
             
         
       
     
     wherein, the derivation occurs at a cysteine residue; R is selected from: 
     
       
         
         
             
             
         
       
     
     wherein R 1  is H, C1-C3 alkyl, or aryl; and F′ is a small molecule fragment moiety. In some embodiments, F′ has a molecular weight of about 175, 200, 225, 250, 275, 300, 350, 400, 450, 500, 550, 600, 650, 700, 750, 800, 850, 900, 950, 1000 Dalton, or higher. In some embodiments, the molecular weight of F′ is prior to enrichment with a halogen, a nonmetal, or a transition metal. In some embodiments, the molecular weight of the small molecule fragment is calculated based on carbon and hydrogen atoms and optionally further based on nitrogen, oxygen and/or sulfur atoms. In some embodiments, the molecular weight of the small molecule fragment does not include the molecular weight of a halogen, a transition metal or a combination thereof. In some embodiments, F′ is a small molecule fragment moiety illustrated in  FIG. 3 . In some embodiments, the cysteine containing protein is a cysteine containing protein described herein. In some embodiments, the cysteine containing protein is a protein illustrated in Tables 1, 2, 3, 8 or 9. In some embodiments, the cysteine containing protein is a protein illustrated in Table 1. In some embodiments, the cysteine containing protein is a protein illustrated in Table 2. In some embodiments, the cysteine containing protein is a protein illustrated in Table 3. In some embodiments, the cysteine containing protein is a protein illustrated in Table 8. In some embodiments, the cysteine containing protein is a protein illustrated in Table 9. 
     Disclosed herein, in certain embodiments, is a derivative of IDH1 protein having the structure of Formula (I), 
     
       
         
         
             
             
         
       
     
     wherein, the derivation occurs at IDH1 cysteine residue position 269 based on SEQ ID NO: 1; R is selected from: 
     
       
         
         
             
             
         
       
     
     wherein R 1  is H, C1-C3 alkyl, or aryl, and F′ is a small molecule fragment moiety. In some embodiments, F′ has a molecular weight of about 175, 200, 225, 250, 275, 300, 350, 400, 450, 500, 550, 600, 650, 700, 750, 800, 850, 900, 950, 1000 Dalton, or higher. In some embodiments, the molecular weight of F′ is prior to enrichment with a halogen, a nonmetal, or a transition metal. In some embodiments, the molecular weight of the small molecule fragment is calculated based on carbon and hydrogen atoms and optionally further based on nitrogen, oxygen and/or sulfur atoms. In some embodiments, the molecular weight of the small molecule fragment does not include the molecular weight of a halogen, a transition metal or a combination thereof. In some embodiments, F′ is a small molecule fragment moiety illustrated in  FIG. 3 . 
     Disclosed herein, in certain embodiments, is a derivative of IDH2 protein having the structure of Formula (I), 
     
       
         
         
             
             
         
       
     
     wherein the derivation occurs at IDH2 cysteine residue position 308 based on SEQ ID NO: 2; R is selected from: 
     
       
         
         
             
             
         
       
     
     wherein R 1  is H, C1-C3 alkyl, or aryl; and F′ is a small molecule fragment moiety. In some embodiments, F′ has a molecular weight of about 175, 200, 225, 250, 275, 300, 350, 400, 450, 500, 550, 600, 650, 700, 750, 800, 850, 900, 950, 1000 Dalton, or higher. In some embodiments, the molecular weight of F′ is prior to enrichment with a halogen, a nonmetal, or a transition metal. In some embodiments, the molecular weight of the small molecule fragment is calculated based on carbon and hydrogen atoms and optionally further based on nitrogen, oxygen and/or sulfur atoms. In some embodiments, the molecular weight of the small molecule fragment does not include the molecular weight of a halogen, a transition metal or a combination thereof. In some embodiments, F′ is a small molecule fragment moiety illustrated in  FIG. 3 . 
     Disclosed herein, in certain embodiments, is a derivative of caspase-8 protein having the structure of Formula (I) 
     
       
         
         
             
             
         
       
     
     wherein the derivation occurs at caspase-8 cysteine residue position 360 based on SEQ ID NO: 3; R is selected from: 
     
       
         
         
             
             
         
       
     
     wherein R 1  is H, C1-C3 alkyl, or aryl; and F′ is a small molecule fragment moiety. In some embodiments, F′ has a molecular weight of about 175, 200, 225, 250, 275, 300, 350, 400, 450, 500, 550, 600, 650, 700, 750, 800, 850, 900, 950, 1000 Dalton, or higher. In some embodiments, the molecular weight of F′ is prior to enrichment with a halogen, a nonmetal, or a transition metal. In some embodiments, the molecular weight of the small molecule fragment is calculated based on carbon and hydrogen atoms and optionally further based on nitrogen, oxygen and/or sulfur atoms. In some embodiments, the molecular weight of the small molecule fragment does not include the molecular weight of a halogen, a transition metal or a combination thereof. In some embodiments, F′ is a small molecule fragment moiety illustrated in  FIG. 3 . 
     Disclosed herein, in certain embodiments, is a derivative of caspase-10 protein having the structure of Formula (I), 
     
       
         
         
             
             
         
       
     
     wherein the derivation occurs at caspase-10 cysteine residue position 401 based on SEQ ID NO: 4; R is selected from: 
     
       
         
         
             
             
         
       
     
     wherein R 1  is H, C1-C3 alkyl, or aryl; and F′ is a small molecule fragment moiety. In some embodiments, F′ has a molecular weight of about 175, 200, 225, 250, 275, 300, 350, 400, 450, 500, 550, 600, 650, 700, 750, 800, 850, 900, 950, 1000 Dalton, or higher. In some embodiments, the molecular weight of F′ is prior to enrichment with a halogen, a nonmetal, or a transition metal. In some embodiments, the molecular weight of the small molecule fragment is calculated based on carbon and hydrogen atoms and optionally further based on nitrogen, oxygen and/or sulfur atoms. In some embodiments, the molecular weight of the small molecule fragment does not include the molecular weight of a halogen, a transition metal or a combination thereof. In some embodiments, F′ is a small molecule fragment moiety illustrated in  FIG. 3 . 
     Disclosed herein, in certain embodiments, is a derivative of PRMT-1 protein having the structure of Formula (I), 
     
       
         
         
             
             
         
       
     
     wherein the derivation occurs at PRMT-1 cysteine residue position 109 based on SEQ ID NO: 5; R is selected from: 
     
       
         
         
             
             
         
       
     
     wherein R 1  is H, C1-C3 alkyl, or aryl; and F′ is a small molecule fragment moiety. In some embodiments, F′ has a molecular weight of about 175, 200, 225, 250, 275, 300, 350, 400, 450, 500, 550, 600, 650, 700, 750, 800, 850, 900, 950, 1000 Dalton, or higher. In some embodiments, the molecular weight of F′ is prior to enrichment with a halogen, a nonmetal, or a transition metal. In some embodiments, the molecular weight of the small molecule fragment is calculated based on carbon and hydrogen atoms and optionally further based on nitrogen, oxygen and/or sulfur atoms. In some embodiments, the molecular weight of the small molecule fragment does not include the molecular weight of a halogen, a transition metal or a combination thereof. In some embodiments, F′ is a small molecule fragment moiety illustrated in  FIG. 3 . 
     Disclosed herein, in certain embodiments, is a derivative of ZAK protein having the structure of Formula (I), 
     
       
         
         
             
             
         
       
     
     wherein the derivation occurs at ZAK cysteine residue position 22 based on SEQ ID NO: 6; R is selected from: 
     
       
         
         
             
             
         
       
     
     wherein R 1  is H, C1-C3 alkyl, or aryl; and F′ is a small molecule fragment moiety. In some embodiments, F′ has a molecular weight of about 175, 200, 225, 250, 275, 300, 350, 400, 450, 500, 550, 600, 650, 700, 750, 800, 850, 900, 950, 1000 Dalton, or higher. In some embodiments, the molecular weight of F′ is prior to enrichment with a halogen, a nonmetal, or a transition metal. In some embodiments, the molecular weight of the small molecule fragment is calculated based on carbon and hydrogen atoms and optionally further based on nitrogen, oxygen and/or sulfur atoms. In some embodiments, the molecular weight of the small molecule fragment does not include the molecular weight of a halogen, a transition metal or a combination thereof. In some embodiments, F′ is a small molecule fragment moiety illustrated in  FIG. 3 . 
     Disclosed herein, in certain embodiments, is a derivative of IMPDH2 protein having the structure of Formula (I), 
     
       
         
         
             
             
         
       
     
     wherein the derivation occurs at IMPDH2 cysteine residue position 140 based on SEQ ID NO: 7; R is selected from: 
     
       
         
         
             
             
         
       
     
     wherein R 1  is H, C1-C3 alkyl, or aryl; and F′ is a small molecule fragment moiety. In some embodiments, F′ has a molecular weight of about 175, 200, 225, 250, 275, 300, 350, 400, 450, 500, 550, 600, 650, 700, 750, 800, 850, 900, 950, 1000 Dalton, or higher. In some embodiments, the molecular weight of F′ is prior to enrichment with a halogen, a nonmetal, or a transition metal. In some embodiments, the molecular weight of the small molecule fragment is calculated based on carbon and hydrogen atoms and optionally further based on nitrogen, oxygen and/or sulfur atoms. In some embodiments, the molecular weight of the small molecule fragment does not include the molecular weight of a halogen, a transition metal or a combination thereof. In some embodiments, F′ is a small molecule fragment moiety illustrated in  FIG. 3 . 
     Disclosed herein, in certain embodiments, is a derivative of IMPDH2 protein having the structure of Formula (I), 
     
       
         
         
             
             
         
       
     
     wherein the derivation occurs at IMPDH2 cysteine residue position 331 based on SEQ ID NO: 7; R is selected from: 
     
       
         
         
             
             
         
       
     
     wherein R 1  is H, C1-C3 alkyl, or aryl; and F′ is a small molecule fragment moiety. In some embodiments, F′ has a molecular weight of about 175, 200, 225, 250, 275, 300, 350, 400, 450, 500, 550, 600, 650, 700, 750, 800, 850, 900, 950, 1000 Dalton, or higher. In some embodiments, the molecular weight of F′ is prior to enrichment with a halogen, a nonmetal, or a transition metal. In some embodiments, the molecular weight of the small molecule fragment is calculated based on carbon and hydrogen atoms and optionally further based on nitrogen, oxygen and/or sulfur atoms. In some embodiments, the molecular weight of the small molecule fragment does not include the molecular weight of a halogen, a transition metal or a combination thereof. In some embodiments, F′ is a small molecule fragment moiety illustrated in  FIG. 3 . 
     Disclosed herein, in certain embodiments, is a derivative of TIGAR protein having the structure of Formula (I), 
     
       
         
         
             
             
         
       
     
     wherein the derivation occurs at TIGAR cysteine residue position 114 based on SEQ ID NO: 8; R is selected from: 
     
       
         
         
             
             
         
       
     
     wherein R 1  is H, C1-C3 alkyl, or aryl; and F′ is a small molecule fragment moiety. In some embodiments, F′ has a molecular weight of about 175, 200, 225, 250, 275, 300, 350, 400, 450, 500, 550, 600, 650, 700, 750, 800, 850, 900, 950, 1000 Dalton. or higher. In some embodiments, the molecular weight of F′ is prior to enrichment with a halogen, a nonmetal, or a transition metal. In some embodiments, the molecular weight of the small molecule fragment is calculated based on carbon and hydrogen atoms and optionally further based on nitrogen, oxygen and/or sulfur atoms. In some embodiments, the molecular weight of the small molecule fragment does not include the molecular weight of a halogen, a transition metal or a combination thereof. In some embodiments, F′ is a small molecule fragment moiety illustrated in  FIG. 3 . 
     Disclosed herein, in certain embodiments, is a derivative of TIGAR protein having the structure of Formula (I), 
     
       
         
         
             
             
         
       
     
     wherein the derivation occurs at TIGAR cysteine residue position 161 based on SEQ ID NO: 8; R is selected from: 
     
       
         
         
             
             
         
       
     
     wherein R 1  is H, C1-C3 alkyl, or aryl; and F′ is a small molecule fragment moiety. In some embodiments, F′ has a molecular weight of about 175, 200, 225, 250, 275, 300, 350, 400, 450, 500, 550, 600, 650, 700, 750, 800, 850, 900, 950, 1000 Dalton, or higher. In some embodiments, the molecular weight of F′ is prior to enrichment with a halogen, a nonmetal, or a transition metal. In some embodiments, the molecular weight of the small molecule fragment is calculated based on carbon and hydrogen atoms and optionally further based on nitrogen, oxygen and/or sulfur atoms. In some embodiments, the molecular weight of the small molecule fragment does not include the molecular weight of a halogen, a transition metal or a combination thereof. In some embodiments, F′ is a small molecule fragment moiety illustrated in  FIG. 3 . 
     Disclosed herein, in certain embodiments, is a derivative of PKCθ protein having the structure of Formula (I), 
     
       
         
         
             
             
         
       
     
     wherein the derivation occurs at PKCθ cysteine residue position 14 based on SEQ ID NO: 9; R is selected from: 
     
       
         
         
             
             
         
       
     
     wherein R 1  is H, C1-C3 alkyl, or aryl; and F′ is a small molecule fragment moiety. In some embodiments, F′ has a molecular weight of about 175, 200, 225, 250, 275, 300, 350, 400, 450, 500, 550, 600, 650, 700, 750, 800, 850, 900, 950, 1000 Dalton, or higher. In some embodiments, the molecular weight of F′ is prior to enrichment with a halogen, a nonmetal, or a transition metal. In some embodiments, the molecular weight of the small molecule fragment is calculated based on carbon and hydrogen atoms and optionally further based on nitrogen, oxygen and/or sulfur atoms. In some embodiments, the molecular weight of the small molecule fragment does not include the molecular weight of a halogen, a transition metal or a combination thereof. In some embodiments, F′ is a small molecule fragment moiety illustrated in  FIG. 3 . 
     Disclosed herein, in certain embodiments, is a derivative of PKCθ protein having the structure of Formula (I), 
     
       
         
         
             
             
         
       
     
     wherein the derivation occurs at PKCθ cysteine residue position 17 based on SEQ ID NO: 9; R is selected from: 
     
       
         
         
             
             
         
       
     
     wherein R 1  is H, C1-C3 alkyl, or aryl; and F′ is a small molecule fragment moiety. In some embodiments, F′ has a molecular weight of about 175, 200, 225, 250, 275, 300, 350, 400, 450, 500, 550, 600, 650, 700, 750, 800, 850, 900, 950, 1000 Dalton, or higher. In some embodiments, the molecular weight of F′ is prior to enrichment with a halogen, a nonmetal, or a transition metal. In some embodiments, the molecular weight of the small molecule fragment is calculated based on carbon and hydrogen atoms and optionally further based on nitrogen, oxygen and/or sulfur atoms. In some embodiments, the molecular weight of the small molecule fragment does not include the molecular weight of a halogen, a transition metal or a combination thereof. In some embodiments, F′ is a small molecule fragment moiety illustrated in  FIG. 3 . 
     Disclosed herein, in certain embodiments, is a method of identifying a cysteine containing protein as a binding target for a small molecule fragment, comprising: (a) obtaining a set of cysteine-reactive probe-protein complexes from a sample comprising a first cell solution treated with a small molecule fragment and a cysteine reactive probe wherein the cysteine-reactive probe comprises a reactive moiety capable of forming a covalent bond with a cysteine residue located on the cysteine containing protein; (b) analyzing the set of cysteine-reactive probe-protein complexes by a proteomic analysis means; and (c) based on step b), identifying a cysteine containing protein as the binding target for the small molecule fragment. In some embodiments, the method further comprises determining a value of each of the cysteine containing protein from the set of cysteine-reactive probe-protein complexes for identifying a cysteine containing protein as the binding target for the small molecule fragment, wherein the value is determined based on the proteomic analysis means of step b). In some embodiments, the sample further comprises a second cell solution. In some embodiments, the method further comprises contacting the first cell solution with a small molecule fragment for an extended period of time prior to incubating the first cell solution with a first cysteine-reactive probe to generate a first group of cysteine-reactive probe-protein complexes. In some embodiments, the extended period of time is about 5, 10, 15, 20, 30, 60, 90, 120 minutes or longer. In some embodiments, the method further comprises contacting the second cell solution with a second cysteine-reactive probe to generate a second group of cysteine-reactive probe-protein complexes. In some embodiments, the first cysteine-reactive probe and the second cysteine-reactive probe are the same. In some embodiments, the first group and the second group of cysteine-reactive probe-protein complexes comprise the set of cysteine-reactive probe-protein complexes. In some embodiments, the cysteine containing protein is an enzyme, a transporter, a receptor, a channel protein, an adaptor protein, a chaperone, a signaling protein, a plasma protein, transcription related protein, translation related protein, mitochondrial protein, or cytoskeleton related protein. In some embodiments, the cysteine containing protein is a protein illustrated in Table 3. In some embodiments, the cysteine containing protein is a protein illustrated in Table 1, Table 2, Table 8. Table 9, Table 10A, Table 10B, Table 10C, Table 10D or Table 10E. In some embodiments, the small molecule fragment is a small molecule fragment of Formula (I): 
     
       
         
         
             
             
         
       
     
     wherein: RM is a reactive moiety selected from a Michael acceptor moiety, a leaving group moiety, or a moiety capable of forming a covalent bond with the thiol group of a cysteine residue; and F is a small molecule fragment moiety. In some embodiments, the Michael acceptor moiety comprises an alkene or an alkyne moiety. In some embodiments. F is obtained from a compound library. In some embodiments, the compound library comprises ChemBridge fragment library, Pyramid Platform Fragment-Based Drug Discovery, Maybridge fragment library, FRGx from AnalytiCon. TCI-Frag from AnCoreX, Bio Building Blocks from ASINEX, BioFocus 3D from Charles River, Fragments of Life (FOL) from Emerald Bio, Enamine Fragment Library, IOTA Diverse 1500, BIONET fragments library, Life Chemicals Fragments Collection, OTAVA fragment library, Prestwick fragment library, Selcia fragment library, TimTec fragment-based library, Allium from Vitas-M Laboratory, or Zenobia fragment library. In some embodiments, F is a small molecule fragment moiety illustrated in  FIG. 3 . In some embodiments, the cysteine-reactive probe is a cysteine-reactive probe of Formula (II): 
     
       
         
         
             
             
         
       
     
     wherein: RM is a reactive moiety selected from a Michael acceptor moiety, a leaving group moiety, or a moiety capable of forming a covalent bond to the thiol group of a cysteine residue; and AHM is an affinity handle moiety. In some embodiments, the Michael acceptor moiety comprises an alkene or an alkyne moiety. In some embodiments, the affinity handle moiety comprises an affinity handle and a binding moiety that facilitates covalent interaction of the cysteine-reactive probe to a cysteine residue of a cysteine-containing protein. In some embodiments, the binding moiety is a small molecule fragment obtained from a compound library. In some embodiments, the affinity handle comprises a carbodiimide, N-hydroxysuccinimide (NHS) ester, imidoester, pentafluorophenyl ester, hydroxymethyl phosphine, maleimide, haloacetyl, pyridyl disulfide, thiosulfonate, vinylsulfone, hydrazide, alkoxyamine, alkyne, azide, or isocyanate group. In some embodiments, the affinity handle is further conjugated to an affinity ligand. In some embodiments, the affinity ligand comprises a chromophore, a labeling group, or a combination thereof. In some embodiments, the chromophore comprises non-fluorochrome chromophore, quencher, an absorption chromophore, fluorophore, organic dye, inorganic dye, metal chelate, or a fluorescent enzyme substrate. In some embodiments, the labeling group is a biotin moiety, a streptavidin moiety, bead, resin, a solid support, or a combination thereof. In some embodiments, the cysteine-reactive probe is a cysteine-reactive probe illustrated in  FIG. 3 . In some embodiments, the proteomic analysis means comprises a mass spectroscopy method. In some embodiments, the identifying in step c) further comprises (i) locating a first value assigned to a cysteine containing protein from the first group of cysteine-reactive probe-protein complex and a second value of the same cysteine containing protein from the second group of cysteine-reactive probe-protein complex; and (ii) calculating a ratio between the two values assigned to the same cysteine containing protein. In some embodiments, the ratio of greater than 2 indicates that the cysteine containing protein is a candidate for interacting with the small molecule fragment. In some embodiments, the identifying in step c) further comprises calculating a percentage of inhibition of the cysteine-reactive probe to the cysteine containing protein. In some embodiments, the percentage of inhibition of greater than 50%, 60%, 70%, 80%, 90%, or at 100% indicates that the cysteine containing protein is a candidate for interacting with the small molecule fragment. In some embodiments, the method is an in situ method. In some embodiments, the cysteine-reactive probe is not 4-hydroxynonenal or 15-deoxy-Δ12,14-prostaglandin J2. 
     Disclosed herein, modified cysteine containing protein comprising a small molecule fragment having a covalent bond to a cysteine residue of a cysteine containing protein, wherein the small molecule fragment has a molecular weight of about 150 Dalton or higher. In some embodiments, the cysteine containing protein comprises a cysteine residue site denoted in Table 3. In some embodiments, the cysteine containing protein comprises a protein sequence illustrated in Table 1, Table 2. Table 8, Table 9, Table 10A, Table 10B, Table 10C, Table 10D or Table 10E. In some embodiments, the cysteine containing protein is about 20, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 150, 200, 250, 300, 350, 400, 450, 500, 600, 700, 800, 900, 1000 amino acid residues in length or more. In some embodiments, the cysteine residue of the modified cysteine containing protein has the structure SR, wherein R is selected from: 
     
       
         
         
             
             
         
       
     
     wherein R 1  is H, C1-C3 alkyl, or aryl; and F′ is the small molecule fragment moiety. In some embodiments, the small molecule fragment has a molecular weight of about 175, 200, 225, 250, 275, 300, 350, 400, 450, 500, 550, 600, 650, 700, 750, 800, 850, 900, 950, 1000 Dalton, or higher. In some embodiments, the molecular weight of the small molecule fragment is calculated based on carbon and hydrogen atoms and optionally further based on nitrogen, oxygen and/or sulfur atoms. In some embodiments, the modified cysteine containing protein is selected from IDH2, caspase-8, caspase-10 or PRMT1. In some embodiments, IDH2 is modified at cysteine position 308. In some embodiments, caspase-8 is modified at cysteine position 360. In some embodiments, caspase-10 exist in the proform and is modified at cysteine position 401. In some embodiments, PRMT1 is modified at cysteine position 109. In some embodiments, the small molecule fragment is a small molecule fragment of Formula (I): 
     
       
         
         
             
             
         
       
     
     wherein: RM is a reactive moiety selected from a Michael acceptor moiety, a leaving group moiety, or a moiety capable of forming a covalent bond with the thiol group of a cysteine residue; and F is a small molecule fragment moiety. In some embodiments, the Michael acceptor moiety comprises an alkene or an alkyne moiety. In some embodiments. F is obtained from a compound library. In some embodiments, F is a small molecule fragment moiety illustrated in  FIG. 3 . In some embodiments. F further comprises a linker moiety that connects F to the carbonyl moiety. In some embodiments, the small molecule fragment binds irreversibly to the cysteine containing protein. In some embodiments, the small molecule fragment binds reversibly to the cysteine containing protein. 
     Disclosed herein, in certain embodiments, is a method of screening a small molecule fragment for interaction with a cysteine containing protein, comprising: (a) harvesting a set of cysteine-reactive probe-protein complexes from a sample comprising a first cell solution treated with a small molecule fragment and a cysteine reactive probe wherein the cysteine-reactive probe comprises a reactive moiety capable of forming a covalent bond with a cysteine residue located on the cysteine containing protein; (b) analyzing the set of cysteine-reactive probe-protein complexes by a proteomic analysis means; and (c) based on step b), identifying the small molecule fragment as interacting with the cysteine containing protein. In some embodiments, the method further comprises determining a value of each of the cysteine containing protein from the set of cysteine-reactive probe-protein complexes prior to identifying the small molecule fragment as interacting with the cysteine containing protein, wherein the value is determined based on the proteomic analysis means of step b). In some embodiments, the cysteine containing protein is a protein illustrated in Table 3. In some embodiments, the cysteine containing protein is a protein illustrated in Table 1. Table 2, Table 8, Table 9, Table 10A, Table 10B, Table 10C, Table 10D or Table 10E. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
       Various aspects of the invention are set forth with particularity in the appended claims. A better understanding of the features and advantages of the present invention will be obtained by reference to the following detailed description that sets forth illustrative embodiments, in which the principles of the invention are utilized, and the accompanying drawings of which: 
         FIG. 1  illustrates proteome-wide screening of covalent fragments. A. General protocol for competitive isoTOP-ABPP. Cell lysate or intact cells are pre-treated with a fragment electrophile or DMSO and then reacted with an IA-alkyne probe 1. The fragment- and DMSO-treated samples are then conjugated to isotopically-differentiated TEV protease-cleavable biotin tags [light (red) and heavy (blue), respectively] by copper-mediated azide-alkyne cycloaddition (CuAAC or click) chemistry, mixed, and IA-labeled proteins enriched by streptavidin-conjugated beads and digested stepwise on-bead with trypsin and TEV to yield IA-labeled peptides for MS analysis. Competition ratios, or R values, are measured by dividing the MS1 ion peaks for IA-labeled peptides in DMSO-treated (heavy or blue) versus fragment-treated (light or red) samples. B, Representative members of the electrophilic fragment library, where the reactive (electrophilic) and binding groups are colored green and black, respectively. C, Initial analysis of the proteomic reactivity of fragments using an IA-rhodamine probe 16. Soluble proteome from Ramos cells was treated with the indicated fragments (500 μM each) for 1 h, followed by labeling with IA-rhodamine (1 μM, 1 h) and analysis by SDS-PAGE and in-gel fluorescence scanning. Several proteins were identified that show impaired reactivity with IA-rhodamine in the presence of one or more fragments (asterisks). Fluorescent gel shown in grayscale. D, Competitive isoTOP-ABPP analysis of fragment-cysteines interactions in the soluble proteome of MDA-MB-231 cells pre-treated with the following fragments (500 μM each): 3,5-di(trifluoromethyl)aniline chloroacetamide 3, acrylamide 14, and acetamide 17. Proteomic reactivity values, or liganded cysteine rates, for fragments were calculated as the percentage of total cysteines with R values≥4 in DMSO/fragment (heavy/light) comparisons. E, Concentration-dependent labeling of MDA-MB-231 soluble proteomes with acrylamide 18 and chloroacetamide 19 click probes detected by CuACC with a rhodamine-azide tag and analysis by SDS-PAGE and in-gel fluorescence scanning. F, Representative MS1 peptide ion chromatograms from competitive isoTOP-ABPP experiments performed with fragments 3, 4, and 23 marking liganded cysteines selectively targeted by one of three fragments (or, in the case of PHGDH C369, by all three fragments). 
         FIG. 2  illustrates a conceptual schematic of an exemplary computer server to be used for processing a method described herein. 
         FIG. 3  shows composition of fragment electrophile library and structures of additional tool compounds, click probes, and fragments. 
         FIG. 4  illustrates analysis of proteomic reactivities of fragment electrophiles determined by competitive isoTOP-ABPP in human cell lysates. A, Frequency of quantification of all cysteines across the complete set of competitive isoTOP-ABPP experiments performed with fragment electrophiles. Note that cysteines were required to have been quantified in at least three isoTOP-ABPP data sets for interpretation. B, Rank order of proteomic reactivity values (or liganded cysteine rates) of fragments calculated as the percentage of all quantified cysteines with R values≥4 for each fragment. The majority of fragments were evaluated in 2-4 replicate experiments in MDA-MB-231 and/or Ramos cell lysates, and their proteomic reactivity values are reported as mean±SEM values for the replicates. C, Comparison of the proteomic reactivities of representative fragments screened at 500 versus 25 μM in cell lysates. D, Comparison of proteomic reactivity values for fragments tested in both Ramos and MDA-MB-231 lysates. E, Mean±SEM data for proteomic reactivity values of representative fragments tested in at least three independent replicates. F, Relative GSH reactivity for representative fragment electrophiles. Consumption of GSH (125 μM) was measured using Ellman&#39;s reagent (5 mM) after 1 h incubation with the indicated fragments (500 μM). G, Proteomic reactivity values for fragments electrophiles (500 μM) possessing different electrophilic groups attached to a common binding element. 
         FIG. 5  illustrates analysis of cysteines and proteins liganded by fragment electrophiles. A, Fraction of total quantified cysteines and proteins that were liganded by fragment electrophiles in competitive isoTOP-ABPP experiments. B, Fraction of liganded proteins found in DrugBank. C, Functional classes of DrugBank and non-DrugBank proteins containing liganded cysteines. D, Functional categorization of liganded and unliganded cysteines based on residue annotations from the Uniprot database. E, Comparison of the ligandability of cysteines as a function of their intrinsic reactivity with the IA-alkyne probe. Cysteine reactivity values were taken from Weerapana, et al.  Nature  468, 790-795 (2010), where lower ratios correspond to higher cysteine reactivity. Individual cysteines are plotted on the x-axis and were sorted by reactivity, which is shown on the left y-axis. A moving average with a step-size of 50 is shown in blue for the percentage of liganded cysteines within each reactivity bin (percent values shown on the right y-axis). F, Number of liganded and quantified cysteines per protein measured by isoTOP-ABPP. Respective average values of one and three for liganded and quantified cysteines per protein were measured by isoTOP-ABPP. G, R values for six cysteines in XPO1 quantified by isoTOP-ABPP, identifying C528 as the most liganded cysteine in this protein. Each point represents a distinct fragment-cysteine interaction quantified by isoTOP-ABPP. 
         FIG. 6  illustrates analysis of fragment-cysteine interactions. A, Heatmap showing R values for representative cysteines and fragments organized by proteomic reactivity values (high to low, left to right) and percentage of fragment hits for individual cysteines (high to low, top to bottom). R values≥4 designate fragment hits (colored medium and dark blue). White color designates fragment-cysteine interactions that were not detected (ND). B, C, Histograms depicting the percentage of fragments that are hits (R≥4) for all 768 liganded cysteines (B) or for liganded cysteines found in enzymes for which X-ray and/or NMR structures have been reported (or reported for a close homologue of the enzyme) (C). D, Percentage of liganded cysteines targeted only by group A (red) or B (blue) fragments or both group A and B fragments (black). Shown for all liganded cysteines, liganded cysteines in enzyme active and non-active sites, and liganded cysteines in transcription factors/regulators. For C, D, active-site cysteines were defined as those that reside &lt;10 Å from established active-site residues and/or bound substrates/inhibitors in enzyme structures. E, Representative example of reactive docking predictions shown for XPO1 (PDB ID: 3GB8). All accessible cysteines were identified and reactive docking was conducted with all fragments from the library within a 25 Å docking cube centered on each accessible cysteine. Categories of XPO1 cysteines based on combined docking and isoTOP-ABPP results are shown. F, Success rate of reactive docking predictions for liganded cysteines identified by isoTOP-ABPP in 29 representative proteins. 
         FIG. 7  illustrates analysis of cysteines liganded by fragment electrophiles in competitive isoTOP-ABPP experiments. A, Representative MS1 ion chromatograms for peptides containing C481 of BTK and C131 of MAP2K7, two cysteines known to be targeted by the anti-cancer drug ibrutinib. Ramos cells were treated with ibrutinib (1 μM, 1 h, red trace) or DMSO (blue trace) and evaluated by isoTOP-ABPP. B, Total number of liganded cysteines found in the active sites and non-active sites of enzymes for which X-ray and/or NMR structures have been reported (or reported for a close homologue of the enzyme). C, R values for eight cysteines in PHGDH quantified by isoTOP-ABPP, identifying a single liganded cysteine C369 that is targeted by several fragment electrophiles. Each point represents a distinct fragment-cysteine interaction quantified by isoTOP-ABPP. D, Heatmap showing representative fragment interactions for liganded cysteines found in the active sites and non-active sites of kinases. E, Histogram showing the fragment hit rate for active- and non-active site cysteines in kinases. F, The percentage of liganded cysteines in kinases that were targeted by only group A, only group B, or both group A and B compounds. G, Heatmap showing representative fragment interactions for liganded cysteines found in transcription factors/regulators. H, The fraction of cysteines predicted to be ligandable or not ligandable by reactive docking that were quantified in isoTOP-ABPP experiments. 
         FIG. 8  illustrates confirmation and functional analysis of fragment-cysteine interactions. A, Representative MS1 chromatograms for the indicated Cys-containing peptides from PRMT1 quantified in competitive isoTOP-ABPP experiments of MDA-MB-231 cell lysates, showing blockade of IA-alkyne 1 labeling of C109 by fragment 11, but not control fragment 3. B, 11, but not 3 blocked IA-rhodamine (2 μM) labeling of recombinant, purified WT-PRMT1 (1 μM protein doped into HEK293T cell lysates). Note that a C109S-PRMT1 mutant did not react with IA-rhodaminc. C, IC 50  curve for blockade of 16 labeling of PRMT1 by 11. CI, 95% confidence intervals. D, Effect of 11 and control fragment 3 on methylation of recombinant histone 4 by recombinant PRMT1. Shown is one representative experiment of three independent experiments that yielded similar results. E, 60, but not control fragment 3 (50 μM of each fragment) blocked labeling of recombinant MLTK (or ZAK) kinase by a previously reported ibrutinib-derived activity probe 59 (upper panel). A C22A-MLTK mutant did not react with the ibrutinib probe. Anti-FLAG blotting confirmed similar expression of WT- and C22A-MLTK proteins, which were expressed as FLAG-fusion proteins in HEK293T cells (lower panel). F, IC 50  curve for blockade of ibrutinib probe-labeling of MLTK by 60. G, 60, but not control fragment 3 (100 μM of each fragment) inhibited the kinase activity of WT-, but not C22A-MLTK. H, Click probe 18 (25 μM) labeled WT-IMPDH2 and C331S-IMPDH2, but not C140S-IMPDH2 (or C140S/C331S-IMPDH2). Labeling was detected by CuAAC conjugation to a rhodamine-azide reporter tag and analysis by SDS-PAGE and in-gel fluorescence scanning. Recombinant IMPDH2 WT and mutants were expressed and purified from  E. coli  and added to Jurkat lysates to a final concentration of 1 μM protein. I, Nucleotide competition profile for 18-labeling of recombinant WT-IMPDH2 (500 μM of each nucleotide). J, IC 50  curve for blockade of 18 labeling of IMPDH2 by ATP. K, 5, but not control fragment 3 blocked IA-rhodamine (2 μM) labeling of recombinant, purified C161S-TIGAR (2 μM protein doped into Ramos cell lysates). L, IC 50  curve for blockade of IA-rhodamine labeling of C161S-TIGAR by 5. M, 5, but not control fragment 3 (100 μM of each fragment) inhibited the catalytic activity of WT-TIGAR, C161S-TIGAR, but not C114S-TIGAR or C114S/C161S-TIGAR. For panels C, F, C, I, J, L, and M, data represent mean values±SEM for at least three independent experiments. Statistical significance was calculated with unpaired students t-tests comparing DMSO- to fragment-treated samples; **, p&lt;0.01, ****, p&lt;0.0001. 
         FIG. 9  illustrates confirmation and functional analysis of fragment-cysteine interactions. A, Representative MS1 ion chromatograms for the MLTK tryptic peptide containing liganded cysteine C22 quantified by isoTOP-ABPP in MDA-MB-231 lysates treated with fragment 4 or control fragment 3 (500 μM each). B, Lysates from HEK293T cells expressing WT- or C22A-MLTK treated with the indicated fragments and then an ibrutinib-derived activity probe 59 at 10 μM. MLTK labeling by 59 was detected by CuAAC conjugation to a rhodamine-azide tag and analysis by SDS-PAGE and in-gel fluorescence scanning. C, Representative MS1 ion chromatograms for IMPDH2 tryptic peptides containing the catalytic cysteine. C331, and Bateman domain cysteine. C140, quantified by isoTOP-ABPP in cell lysates treated with the indicated fragments (500 μM each). D, Structure of human IMPDH2 (PDB ID: INF7) (light grey) and its structurally unresolved Bateman domain modeled by ITASSER (dark grey) showing the positions of C331 (red spheres), Ribavirin Monophosphate and C2-Mycophenolic Adenine Dinucleotide (blue), and C140 (yellow spheres). E, Fragment reactivity with recombinant, purified IMPDH2 added to Jurkat lysates to a final concentration of 1 μM protein, where reactivity was detected in competition assays using the click probe 18 (25 μM; see  FIG. 8H  for structure of 18). Note that 18 reacted with WT- and C331S-IMPDH2, but not C140S or C140S/C331S-IMPDH2. F. Nucleotide competition of 18 (25 μM) labeling of WT-IMPDH2 added to cell lysates to a final concentration of 1 μM protein. G, Representative MS1 chromatograms for TIGAR tryptic peptides containing C114 and C161 quantified by isoTOP-ABPP in cell lysates treated with the indicated fragments (500 μM each). H, Crystal structure of TIGAR (PDB ID: 3DCY) showing C114 (red spheres), C161 (yellow spheres), and inorganic phosphate (blue). I, Labeling of recombinant, purified TIGAR and mutant proteins by the IA-rhodamine (2 μM) probe. TIGAR proteins were added to cell lysates, to a final concentration of 2 μM protein. J, Concentration-dependent inhibition of WT-TIGAR by 5. Note that the C140S-TIGAR mutant was not inhibited by 5. Data represent mean values±SEM for 4 replicate experiments at each concentration. 
         FIG. 10  illustrates in situ activity of fragment electrophiles. A. X-ray crystal structure of IDH1 (PDB ID: 3MAS) showing the position of C269 and the frequently mutated residue in cancer, R132, B, C, Reactivity of 20 and control fragment 2 with recombinant, purified WT-IDH1 (B) or R132H-IDH1 (C) added to cell lysates to a final concentration of 2 or 4 μM protein, respectively. Fragment reactivity was detected in competition assays using the IA-rhodamine probe (2 μM); note that the C269S-IDH1 mutant did not react with IA-rhodamine. D, Representative MS1 ion chromatograms for the IDH1 tryptic peptides containing liganded cysteine C269 and an unliganded cysteine C379 quantified by isoTOP-ABPP in MDA-MB-231 lysates treated with fragment 20 (25 μM). E, Western blot of MUM2C cells stably overexpressing GFP (mock) or R132H-IDH1 proteins. F, Representative MS1 chromatograms for the IDH1 tryptic peptides containing liganded cysteine C269 and an unliganded cysteine C379 quantified by isoTOP-ABPP in R132H-IDH-expressing MUM2C lysates treated with 20 or control fragment 2 (5 μM, 2 h, in situ). 
         FIG. 11  illustrates in situ activity of fragment electrophiles. A, Blockade of 16 labeling of WT-IDH1 by representative fragment electrophiles. Recombinant, purified WT-IDH1 was added to MDA-MB-231 lysates at a final concentration of 2 μM, treated with fragments at the indicated concentrations, followed by IA-rhodamine probe 16 (2 μM) and analysis by SDS-PAGE and in-gel fluorescence scanning. Note that a C269S mutant of IDH1 did not label with IA-rhodamine 16. B. IC 50  curve for blockade of IA-rhodamine-labeling of IDH1 by 20. Note that the control fragment 2 showed much lower activity. C, 20, but not 2, inhibited IDH1-catalyzed oxidation of isocitrate to α-ketoglutarate (α-KG) as measured by an increase in NADPH production (340 nm absorbance). 20 did not inhibit the C269S-IDH1 mutant. D, 20 inhibited oncometabolite 2-hydroxyglutarate (2-HG) production by R132H-IDH1. MUM2C cells stably overexpressing the oncogenic R132H-IDH1 mutant or control GFP-expressing MUM2C cells were treated with the indicated fragments (2 h, in situ). Cells were harvested, lysed and IDH I-dependent production of 2-HG from α-KG and NADPH was measured by LC-MS and from which 2-HG production of GFP-expressing MUM2C cells was subtracted (GFP-expressing MUM2C cells produced &lt;10% of the 2-HG generated by R132H-IDH1-expressing MUM2C cells). E, Proteomic reactivity values for individual fragments are comparable in vitro and in situ. One fragment (11) marked in red showed notably lower reactivity in situ versus in vitro. Reactivity values were calculated as in  FIG. 1D . Dashed line mark 90% prediction intervals for the comparison of in vitro and in situ proteomic reactivity values for fragment electrophiles. Blue and red circles mark fragments that fall above (or just at) or below these prediction intervals, respectively. F. Fraction of cysteines liganded in vitro that is also liganded in situ. Shown are liganded cysteine numbers for individual fragments determined in vitro and the fraction of these cysteines that were liganded by the corresponding fragments in situ. G, Representative cysteines that were selectively targeted by fragments in situ, but not in vitro. For in situ-restricted fragment-cysteine interactions, a second cysteine in the parent protein was detected with an unchanging ratio (R˜1), thus controlling for potential fragment-induced changes in protein expression. For panels B-D, data represent mean values±SEM for at least three independent experiments. Statistical significance was calculated with unpaired students t-tests comparing DMSO- to fragment-treated samples; ****, p&lt;0.0001. 
         FIG. 12  illustrates fragment electrophiles that target pro-CASP8. A, Representative MS1 chromatograms for CASP8 tryptic peptide containing the catalytic cysteine C360 quantified by isoTOP-ABPP in cell lysates or cells treated with fragment 4 (250 μM, in vitro; 100 μM, in situ) and control fragment 21 (500 μM, in vitro; 200 μM, in situ). B, Fragment reactivity with recombinant, purified active CASP8 added to cell lysates, where reactivity was detected in competition assays using the caspase activity probe Rho-DEVD-AOMK probe (“DEVD” disclosed as SEQ ID NO: 857) (2 μM, 1 h). C, Western blot of proteomes from MDA-MB-231, Jurkat, and CASP8-null Jurkat proteomes showing that CASP8 was only found in the pro-enzyme form in these cells. D, Fragment reactivity with recombinant, purified pro-CASP8 (D374A, D384A, C409S) added to cell lysates to a final concentration of 1 μM protein, where reactivity was detected in competition assays with the IA-rhodamine probe (2 μM). Note that mutation of both cysteine-360 and cysteine-409 to serine prevented labeling of pro-CASP8 by IA-rhodamine. E, Concentration-dependent reactivity of click probe 61, with recombinant, purified pro-CASP8 (D374A, D384A) added to cell lysates to a final concentration of 1 μM protein. Note that pre-treatment with 7 blocked 61 reactivity with pro-CASP8 and mutation of C360 to serine prevented labeling of pro-CASP8 by 61 (25 μM). F, Fragments 7 and 62 did not block labeling by Rho-DEVD-AOMK (“DEVD” disclosed as SEQ ID NO: 857) (2 μM) of recombinant, purified active-CASP8 and active-CASP3 added to MDA-MB-231 cell lysates to a final concentration of 1 μM protein. G, Representative MS1 chromatograms for tryptic peptides containing the catalytic cysteines of CASP8 (C360), CASP2 (C320), and CASP7 (C186) quantified by isoTOP-ABPP in Jurkat cell lysates treated with 7 or 62 (50 μM, 1 h). H, Representative MS1 chromatograms for CASP8 trvptic peptide containing C360 quantified by isoTOP-ABPP in cell lysates treated with 10 versus 100 μM of 61. Structure of CASP8 C360 tryptic peptide adduct (blue) modified by 61 (black) and conjugated to TEV cleavable tag (red), where underline indicates site of isotopic modification. Figure discloses SEQ ID NO: 864. 
         FIG. 13  illustrates fragment electrophiles that target pro-CASP8. A,  7  blocked IA-rhodamine 16 labeling of pro-CASP8. Experiments were performed with recombinant, purified pro-CASP8 (bearing a C409S mutation to eliminate IA-rhodamine labeling at this site) added to Ramos cell lysate at a final concentration of 1 μM and treated with the indicated concentrations of 7 followed by IA-rhodamine (2 μM). Note that a C360S/C409S-mutant of pro-CASP8 did not label with IA-rhodamine. B, IC 50  curve for blockade of IA-rhodamine labeling of pro-CASP8 (C409S) by 7. C, 7 (50 μM) fully competed IA-alkyne-labeling of C360 of endogenous CASP8 in cell lysates as measured by isoTOP-ABPP. Representative MS1 chromatograms are shown for the C360-containing peptide of CASP8. D, 7 selectively blocked probe labeling of pro-CASP8 compared to active CASP8. Recombinant pro- and active-CASP8 (added to Ramos cell lysates at a final concentration of 1 μM each) were treated with 7 (50 μM) or the established caspase inhibitor. Ac-DEVD-CHO (“DEVD” disclosed as SEQ ID NO: 857) (20 μM), for 1 h followed by labeling with the click probe 61 (25 μM) for pro-CASP8 and the Rho-DEVD-AOMK probe (“DEVD” disclosed as SEQ ID NO: 857) (2 μM) for active-CASP8. SDS-PAGE and in-gel fluorescence scanning revealed that 7 competes 61-labeling of pro-CASP8, but not Rho-DEVD-AOMK (“DEVD” disclosed as SEQ ID NO: 857) of active-CASP8, and, conversely, DEVD-CHO (“DEVD” disclosed as SEQ ID NO: 857) competed Rho-DEVD-AOMK (“DEVD” disclosed as SEQ ID NO: 857) labeling of active-CASP8, but not 61-labeling of pro-CASP8. E, Neither 7 nor control fragment 62 (100 μM each) inhibited the activity of recombinant, purified active CASP8 and CASP3, which were assayed following addition to Ramos cell lysate using DEVD-AMC and IETD-AFC substrates, respectively. DEVD-CHO (“DEVD” disclosed as SEQ ID NO: 857) (20 μM) inhibited the activity of both CASP8 and CASP3. F, 7 (30 μM) blocked IA-alkyne labeling of C360 of pro-CASP8, but not active-CASP8 as measured by isoTOP-ABPP. Recombinant pro- and active-CASP8 were added to Ramos lysates at 1 μM and then treated with 7 (30 μM) followed by isoTOP-ABPP. G, Substitution of a naphthylamine for the aniline portion of 7 furnishes a control fragment 62 that did not compete with IA-rhodamine labeling of C360 of pro-CASP8. H, 7, but not control fragment 62, blocked extrinsic, but not intrinsic apoptosis. Jurkat cells (1.5 million cells/mL) were incubated with 7 or 62 (30 μM) or the pan-caspase inhibitor VAD-FMK (100 μM) for 30 min prior to addition of staurosporine (2 μM) or SuperFasLigand™ (100 ng/mL). Cells were incubated for 6 hours and viability was quantified with CellTiter-Glo®. RLU—relative light unit. I, For cells treated as described in H, cleavage of PARP (89 kDa), CASP8 (p43/p41), and CASP3 (p19/p17) was visualized by western blot. For panels B, E, and H, data represent mean values±SEM for at least three independent experiments. 
         FIG. 14  shows electrophile compounds that target pro-CASP8 and pro-CASP10. Heatmap showing R values for caspases measured by quantitative proteomics in Jurkat cells treated with 7, 63-R, or 62 followed by probe 61 (10 μM, 1 h) (A). Comparison of effects of 7 and 63-R on FasL-induced apoptosis in Jurkat cells or anti-CD3, anti-CD28-activated primary human T cells (B). For B, data represent mean values±SEM for at least three independent experiments, and results are representative of multiple experiments performed with T cells from different human subjects. Statistical significance was calculated with unpaired students t-tests comparing DMSO- to fragment treated samples; ****, p&lt;0.0001 and comparing Jurkat to T cells ####, p&lt;0.0001. 
         FIG. 15  illustrates a fraction of liganded (62%; 341 of 553 quantified cysteines) and unliganded (20%; 561 of 2870 quantified cysteines) cysteines that are sensitive to heat denaturation measured by IA-alkyne labeling (R&gt;3 native/heat denatured). 
         FIG. 16  shows a percentage of proteins identified by isoTOP-ABPP as liganded by fragments 3 and 14 and enriched by their corresponding click probes 19 and 18 that are sensitive to heat denaturation (64% (85 of 133 quantified protein targets) and 73% (19 of 26 quantified protein targets), respectively). Protein enrichment by 18 and 19 was measured by whole protein capture of isotopically-SILAC labeled MDA-MB-231 cells using quantitative (SILAC) proteomics. 
         FIG. 17A - FIG. 17B  illustrate exemplary fractions of cysteines predicted based on isoTOP-ABPP method or IA-alkyne probe.  FIG. 17A  shows the fraction of cysteines predicted to be ligandable or unligandable by reactive docking that were quantified in isoTOP-ABPP experiments.  FIG. 17B  shows the fraction of cysteines predicted to be ligandable or unligandable by reactive docking that show heat-sensitive labeling by the IA-alkyne probe (R&gt;3 native/heat denatured). 
         FIG. 18  shows lysates from HEK293T cells expressing WT or C22A-MLTK treated with the indicated fragments and then an ibrutinib-derived activity probe 59 at 10 μM. MLTK labeling by 59 was detected by CuAAC conjugation to a rhodamine-azide tag and analysis by SDS-PAGE and in-gel fluorescence scanning. 
         FIG. 19  shows click probe 18 (2 μM) labeled WT-IMPDH2 and C331S-IMPDH2, but not C140S-IMPDH2 (or C140S/C331S-IMPDH2). Labeling was detected by CuAAC conjugation to a rhodamine-azide reporter tag and analysis by SDS-PAGE and in-gel fluorescence scanning. Recombinant IMPDH2 WT and mutants were expressed and purified from  E. coli  and added to Jurkat lysates to a final concentration of 1 μM protein. 
         FIG. 20  shows the apparent IC 50  curve for blockade of IA rhodamine-labeling of R132H-IDH1 by 20. 
         FIG. 21A - FIG. 21C  show the activity of compounds 7 and 62 with respect to different recombinant caspases.  FIG. 21A  shows that 7 does not inhibit active caspases. Recombinant, active caspases were added to MDA-MD-231 lysate to a final concentration of 200 nM (CASP2, 3, 6, 7) or 1 gtM (CASP8, 10), treated with z-VAD-FMK (25 μM) or 7 (50 μM), followed by labeling with the Rho-DEVD-AOMK probe (“DEVD” disclosed as SEQ ID NO: 857) (2 μM).  FIG. 21B  shows a western blot of the cleavage of PARP (96 kDa), CASP8 (p43/p41, p18), and CASP3 (p17).  FIG. 21C  shows that 7 protects Jurkat cells from extrinsic, but not intrinsic apoptosis. Cleavage of PARP, CASP8, and CASP3 detected by western blotting as shown in  FIG. 21B  was quantified for three (STS) or two (FasL) independent experiments. Cleavage products (PARP (96 kDa), CASP8 (p43/p4), CASP3 (p17)) were quantified for compound treatment and the % cleavage relative to DMSO treated samples was calculated. For  FIG. 21C , STS data represent mean values±SEM for three independent experiments, and FasL data represent mean values±SD for two independent experiments. Statistical significance was calculated with unpaired students t-tests comparing active compounds (VAD-FMK and 7) to control compound 62; **, p&lt;0.01, ***, p&lt;0.001, ****, p&lt;0.0001. 
         FIG. 22  shows that CASP10 is involved in intrinsic apoptosis in primary human T cells. A, Representative MS1 peptide signals showing R values for caspases detected by quantitative proteomics using probe 61. ABPP-SILAC experiments. Jurkat cells (10 million cells) were treated with either DMSO (heavy cells) or the indicated compounds (light cells) for 2 h followed by probe 61 (10 μM, 1 h). B, 7 competed 61-labeling of pro-CASP8 and CASP10, whereas 63-R selectively blocked probe labeling of pro-CASP8. C, 7, but not 63-R block probe labeling of pro-CASP10. Recombinant pro-CASP10 was added to MDA-MB-231 lysates to a final concentration of 300 nM, treated with the indicated compounds, and labeled with probe 61. Mutation of the catalytic cysteine C401A fully prevented labeling by 61. D, Apparent IC50 curve for blockade of 61-labeling of pro-CASP10 by 7, 63-R or 63-S. E. Neither 7 nor 63 (25 μM each) inhibited the activity of recombinant, purified active CASP10 (500 nM), which was assayed following addition of the protein to MDA-MB-231 lysate using fluorometric AEVD-AMC substrate (“AEVD” disclosed as SEQ ID NO: 859). DEVD-CHO (“DEVD” disclosed as SEQ ID NO: 857) (20 μM) inhibited the activity of CASP10. F, Apparent IC 50  curve for blockade of 61 labeling of pro-CASP8 and pro-CASP0 by 63-R. G, 63-R shows increased potency against pro-CASP8. Recombinant pro-CASP8 was added to MDA-MB-231 lysates to a final concentration of 300 nM, treated with the indicated compounds and labeled with probe 61. H, Apparent IC50 curve for blockade of 61 labeling of pro-CASP8 by 63-R compared with 63-S. The structure of 63-S is shown. I. CASP10 is more highly expressed in primary human T cells compared to Jurkat cells. Western blot analysis of full-length CASP10, CASP8 and GAPDH expression levels in Jurkat and T-cell lysates (2 mg/mL). J, Jurkat cells (150,000 cells/well) were incubated with 7 or 63-R at the indicated concentrations for 30 min prior to addition of staurosporine (2 μM) or SuperFasLigand™ (100 ng/mL). Cells were incubated for 4 h and viability was quantified with CellTiter-Glo®. K, Jurkat cells treated as in J, but with 63-R or 63-S. L, HeLa cells (20,000 cells/well) were seeded and 24 h later treated with the indicated compounds for 30 minutes prior to addition of SuperFasLigandr (100 ng/mL) and cycloheximide (CHX, 2.5 ng/mL). Cells were incubated for 6 h and viability quantified with CTG. M, For T cells treated as in  FIG. 14B  cleavage of CASP10 (p22), CASP8 (p18). CASP3 (p17) and RIPK (33 kDa) was visualized by western blotting. For panels D-F, H, and J-K data represent mean values±SEM for at least three independent experiments. Statistical significance was calculated with unpaired students t-tests comparing DMSO- to fragment-treated samples; **, p&lt;0.01, ****, p&lt;0.0001. 
         FIG. 23A - FIG. 23F  exemplify DMF inhibits the activation of primary human T cells.  FIG. 23A  illustrates the chemical structures of DMF, MMF, and DMS.  FIG. 23B - FIG. 23E  illustrate bar graphs that exemplify IL-2 release ( FIG. 23B ), CD25 expression ( FIG. 23C  and  FIG. 23D ), and CD69 expression ( FIG. 23E ) in primary human T cells, either unstimulated (Unstim) or stimulated (Stim) with anti-CD3+anti-CD28 in the presence of DMSO or the indicated concentrations of DMF, MMF, and DMS for 8 hours.  FIG. 23F  illustrates a bar graph that exemplifies time course of DMF effects. T cells were stimulated with anti-CD3+anti-CD28 for the indicated periods of time before beginning DMF treatment. Cells were harvested 24 h after beginning T cell stimulation. Shown are data gated on CD4+ cells. Data represent mean±SE, n=4-6 experiments/group. *p&lt;0.05, **p&lt;0.01, ***p&lt;0.001 in comparison to DMSO group. 
         FIG. 24  illustrates a bar graph that exemplifies DMF does not affect T cell viability. Primary human T cells were stimulated with anti-CD3 and anti-CD28 antibodies as indicated and treated concomitantly with compound for 8 h. Cells were then stained with LIVE/DEAD fixable blue stain, and analyzed by flow cytometry. Shown are data gated on CD4+ cells. Data represent mean±SE for four experiments per group. 
         FIG. 25A - FIG. 25B  illustrate bar graphs that exemplify DMF, but not MMF, inhibits the activation of primary mouse T cells. Splenic T cells were harvested from C57BL/6 mice and left either unstimulated (Unstim) or stimulated (Stim) with anti-CD3+anti-CD28 in the presence of DMSO or the indicated concentrations of DMF. MMF, and DMS for 8 h. Activation was assessed by measuring CD25 ( FIG. 25A ) and CD69 ( FIG. 25B ) expression. Data represent mean±SE for four experiments per group. ***p&lt;0.001 in comparison to DMSO group. 
         FIG. 26A - FIG. 26D  illustrate bar graphs that exemplify inhibitory effects of DMF are equivalent in Nrf2(+/+) and (−/−) T cells and not caused by reductions in cellular GSH.  FIG. 26A  exemplifies CD25 expression in anti-CD3+anti-CD28-stimulated Nrf2(+/+) and (−/−) T cells. Splenic T cells were harvested from Nrf2(+/+) and (−/−) mice, then stimulated in the presence of indicated compounds for 24 h.  FIG. 26B  and  FIG. 26C  exemplify treatment with DMF or BSO causes significant reductions in GSH content of human T cells. Primary human T cells were stimulated with anti-CD3+anti-CD28 antibodies and treated with DMF (50 μM, 2 hours) or BSO (2.5 mM, 4 hours), after which intracellular GSH levels were measured.  FIG. 26D  exemplifies that BSO does not alter T cell activation. Primary human T cells were treated with DMSO, DMF (50 μM), or BSO (2.5 mM) and stimulated as indicated for 8 h, after which CD25 expression was measured. Data represent mean±SE for two biological replicates, with 3-4 technical replicates per biological replicate. *p&lt;0.05, **p&lt;0.01, ***p&lt;0.001 in comparison to DMSO groups. 
         FIG. 27A - FIG. 27F  exemplify isoTOP-ABPP of DMF-treated primary human T cells.  FIG. 27A  illustrates a graph that exemplifies isoTOP-ABPP ratios, or R values, for &gt;2400 Cys residues in primary human T cells treated with DMSO or DMF or MMF (50 μM, 4 h).  FIG. 27B  illustrates a graph that exemplifies expanded profile for DMF-sensitive Cys residues (R values&gt;4 for DMSO/DMF). For  FIG. 27A  and  FIG. 27B , data represent aggregate quantified Cys residues from five biological replicates. For Cys residues quantified in more than one replicate, average ratios are reported. Dashed line designates R values&gt;4, which was used to define DMF-sensitive Cys residues (&gt;4-fold reductions in IA-alkyne reactivity in DMF-treated T cells).  FIG. 27C  and  FIG. 27D  illustrate graphs that exemplify concentration- and time-dependent profiles for DMF-sensitive Cys residues in T cells, respectively. For additional concentrations (10 and 25 μM) and time points (1 and 2 h), data represent aggregate quantified Cys residues from one-three isoTOP-ABPP experiments per group.  FIG. 27E  illustrates a chart which exemplifies fraction of proteins for which both a DMF-sensitive Cys residue and at least one additional Cys residue was quantified (Left) and, fraction of these proteins where additional Cys residue was clearly unchanged (Right) (R value&lt;2.0 for DMSO/DMF). Unclear calls mark proteins with DMF-sensitive Cys residues where the R value for second Cys showed marginal evidence of potential change (R values between 2.0 and 3.9).  FIG. 27F  illustrates representative MS profiles for quantified Cys residues in PRKDC, one of which (C4045) shows sensitivity to DMF. 
         FIG. 28A - FIG. 28B  illustrate bar graphs that exemplify the total number of unique quantified peptides ( FIG. 28A ) and proteins ( FIG. 28B ) begin to plateau after five biological replicates of the isoTOP-ABPP experiment in primary human T cells (treated with 50 uM DMF for 4 h). 
         FIG. 29  illustrates a graph that exemplifies isoTOP-ABPP of BSO-treated primary human T cells. Cells were treated with 2.5 mM BSO for 4 hours. Data represent aggregate quantified Cys residues from two isoTOP-ABPP experiments per group. 
         FIG. 30A - FIG. 30C  exemplify conservation and functional analysis of DMF-sensitive cysteines.  FIG. 30A  exemplifies fraction of DMF-sensitive cysteines in the human T cell proteome that are conserved in mice.  FIG. 30B  exemplifies fraction of conserved DMF-sensitive Cys residues in human T cells that were quantified and also sensitive to DMF in mouse T cells.  FIG. 30C  exemplifies distribution of proteins harboring DMF-sensitive Cys residues by functional class. 
         FIG. 31A - FIG. 31C  exemplify DMF inhibits p65 translocation to the nucleus in primary human T cells.  FIG. 31A  exemplify Human T cells were either left unstimulated or stimulated with anti-CD3 and anti-CD28 antibodies and treated with DMSO or DMF (50 uM) for 1 h.  FIG. 31B  illustrates a bar graph that exemplifies ratio of nuclear to cytoplasmic localization of p65 for samples shown in  FIG. 31A , as well as samples treated with MMF (50 uM) or DMS (50 uM).  FIG. 31C  exemplifies p65 levels in whole cell lysate. 
         FIG. 32A - FIG. 32G  exemplify DMF-sensitive C14/C17 residues in PKCθ are important for CD28 interactions and T cell activation.  FIG. 32A  illustrates representative MS1 profiles for DMF-sensitive (C14/C17) and -insensitive (C322) Cys residues in PKCθ.  FIG. 32B  exemplifies sequence conservation analysis of human and mouse PKCθ, human PKCδ, and human PKCε (SEQ ID NOS 865-868, respectively, in order of appearance). Shown in red are C14 and C17.  FIG. 32C  illustrates location of DMF-sensitive C14 and C17 residues in the C2 domain of PKCθ (PDB accession number 2ENJ).  FIG. 32D  exemplifies DMF, but not MMF, treatment blocks the association of PKCθ with CD28. Peripheral CD4+ T cells from C57BL/6 mice were pre-incubated with DMSO, DMF (50 μM), or MMF (50 μM), either left unstimulated or stimulated with anti-CD3+anti-CD28 for 5 min, then washed and lysed. Immunoprecipitations (IPs) were performed in the cell lysates with anti-CD28 or control IgG antibodies and IPs blotted for CD28 or PKCθ.  FIG. 32E  illustrates Co-IP of WT PKCθ and the C14S/C17S (2CS) PKCθ mutant with CD28. PKCθ(−/−) T cells were reconstituted with empty vector (EV), WT PKCθ, or the 2CS PKCθ mutant.  FIG. 32F  and  FIG. 32G  illustrate PKCθ(−/−) T cells reconstituted with WT or 2CS PKCθ were assayed for activation potential by measuring CD25 expression ( FIG. 32F ) and IL-2 ( FIG. 32G ). For  FIG. 32E - FIG. 32G , PKCθ(−/−) T cell cultures were pre-activated with plate-coated anti-CD3+anti-CD28 for 24 h before retroviral transduction with empty vector, WT PKCθ, or the 2CS PKCθ mutant. Cells were rested in culture medium without stimulation for 48 h. then re-stimulated with or without 1 μg/mL plate-coated anti-CD3(+28) overnight ( FIG. 32F ), for 48 h ( FIG. 32G ), or with soluble 10 μg/mL anti-CD3+anti-CD28 for 5 min prior to IP ( FIG. 32D ). For  FIG. 32D  and  FIG. 32E , data are from a single experiment representative of three biological replicates. For  FIG. 32F  and  FIG. 32G , data represent mean±SE for three biological replicates. ***p&lt;0.001 in comparison to WT PKCθ group. 
         FIG. 33A - FIG. 33D  exemplify DMF sensitivity of C14/C17 in PKCθ.  FIG. 33A  illustrates representative MS1 profile of C14/C17 of mouse PKCθ shows sensitivity to DMF (50 μM, 4 h) in isoTOP-ABPP experiments.  FIG. 33B  and  FIG. 33C  exemplify Time- and concentration-dependence of DMF sensitivity of C14/C17 in human PKCθ, respectively, as determined by isoTOP-ABPP experiments.  FIG. 33D  exemplifies C14/C17 of human PKCθ are insensitive to MMF treatment (50 μM MMF, 4 h). 
         FIG. 34A - FIG. 34B  exemplify DMF-sensitive Cys residue in ADA.  FIG. 34A  illustrates the DMF-sensitive Cys, C75 (magenta), is ˜25 angstroms from the ADA active site (orange).  FIG. 34B  illustrates mutations in both residues neighboring C75 (G74 and R76 (blue)) have been associated with the severe combined immunodeficiency known as ADASCID (OMIM: 608958). PDB accession number: 3IAR. 
     
    
    
     DETAILED DESCRIPTION OF THE INVENTION 
     Cysteine containing proteins encompass a large repertoire of proteins that participate in numerous cellular functions such as mitogenesis, proliferation, apoptosis, gene regulation, and proteolysis. These proteins include enzymes, transporters, receptors, channel proteins, adaptor proteins, chaperones, signaling proteins, plasma proteins, transcription related proteins, translation related proteins, mitochondrial proteins, or cytoskeleton related proteins. Dysregulated expression of a cysteine containing protein, in many cases, is associated with or modulates a disease, such as an inflammatory related disease, a neurodegenerative disease, or cancer. As such, identification of a potential agonist/antagonist to a cysteine containing protein aids in improving the disease condition in a patient. 
     In some instances, potential constrains exist in drug screening due to the structurally complex compound and the inability of some of the structurally complexed compound to interact with the protein. As such, small molecule fragments are employed in some instances to serve as launching point for structure-guided elaboration of an initial interaction into a high-affinity drug. In some instances, one method of identifying a small molecule fragment that interacts with a cysteine containing protein is through monitoring their interaction under an in vitro environment. However in some cases, the in vitro environment does not mimic the native condition of the cysteine containing protein. In other cases, the in vitro environment lacks additional helper proteins to facilitate interaction with the small molecule fragment. Further still, in some instances, difficulties arise during the expression and/or purification stage of the cysteine-containing protein. 
     Described herein is another method of identifying small molecule fragments for interaction with a cysteine containing protein. In some instances, this method allows for mapping of small molecule fragments for interaction with a cysteine containing protein under native conditions, thereby allows for an accurate mapping of interaction with potential small molecule fragments. In some instances, this method also allows for identification of novel cysteine containing protein targets as this method eliminates the need of recombinant expression and purification. 
     In some embodiments, also described herein are compositions, cells, cell populations, assays, probes, and service related to the method of identifying a small molecule fragment for interaction with a cysteine containing protein. 
     General Methodology 
     In some embodiments, the methods described herein utilize a small molecule fragment and a cysteine-reactive probe for competitive interaction with a cysteine-containing protein. In some embodiments, the method is as described in  FIG. 1A .  FIG. 1A  illustrates contacting a first cell solution with a small molecule fragment for an extended period of time prior to incubating the first cell solution with a first cysteine-reactive probe to generate a first group of cysteine-reactive probe-protein complexes. In some embodiments, the extended period of time is about 5, 10, 15, 20, 30, 60, 90, 120 minutes or longer. In some instances, the small molecule fragment competes with the first cysteine-reactive probe for interaction with a protein target. In some instances, the small molecule fragment or the cysteine-reactive probe form a covalent bond via a Michael&#39;s reaction with a cysteine residue of the cysteine containing protein.  FIG. 1A  further illustrates contacting a second cell solution with a second cysteine-reactive probe to generate a second group of cysteine-reactive probe-protein complexes. In some instances, the first cysteine-reactive probe and the second cysteine-reactive probe are the same. 
     In some embodiments, cells from the second cell solution are grown in an enriched media (e.g., an isotopically enriched media). In some cases, cells from the first cell solution are grown in an enriched media (e.g., an isotopically enriched media). In some instances, cells from both the first cell solution and the second cell solution are grown in two different enriched media (e.g., two different isotopically enriched media) so that a protein obtained from cells grown in the first cell solution is distinguishable from a protein obtained from cells grown in the second cell solution. In other embodiments, cells from only one of the cell solutions (e.g., either the first cell solution or the second cell solution) are grown in an enriched media (e.g., isotopically enriched media). In such cases, a protein obtained from the enriched cells (e.g., isotopically enriched cells) is distinguishable from a protein obtained from cells that have not been enriched (e.g., isotopically enriched). 
     As illustrated in  FIG. 1A , in some instances the second cell solution is not treated with a small molecule fragment. In such cases, the second cell solution acts as a control. 
     In some instants, cells from the second cell solution are ae-further treated with a buffer. In some cases, the buffer is DMSO. In some cases, cells from the second cell solution are not treated with a small molecule fragment and the second cell solution acts as a control. 
     In some instances, a first group of cysteine-reactive probe-protein complexes and a second group of cysteine-reactive probe-protein complexes are harvested separately and combined to generate a set of cysteine-reactive probe-protein complexes which is further processed by a proteomic analysis means. In some cases, either the first group of cysteine-reactive probe-protein complexes or the second group of cysteine-reactive probe-protein complexes contain labeled proteins obtained from cells grown in an enriched media (e.g., isotopically enriched media). In some cases, both groups of cysteine-reactive probe-protein complexes contain labeled proteins obtained from cells grown in two different enriched media (e.g., two different isotopically enriched media). In other cases, either the first group of cysteine-reactive probe-protein complexes, the second group of cysteine-reactive probe-protein complexes, or both groups of cysteine-reactive probe-protein complexes contain labeled proteins in which the proteins have been labeled after harvesting from a cell. 
     In some instances, a first group of cysteine-reactive probe-protein complexes and a second group of cysteine-reactive probe-protein complexes are harvested separately and the proteins from one of the two groups of cysteine-reactive probe-protein complexes are subsequently labeled (e.g., by methylation). In some cases, first group of cysteine-reactive probe-protein complexes and a second group of cysteine-reactive probe-protein complexes are then combined and subjected to proteomic analysis means. 
     In other instances, a first group of cysteine-reactive probe-protein complexes and a second group of cysteine-reactive probe-protein complexes are harvested separately and both groups are subjected to proteomic analysis means. In some cases, data obtained from a proteomic analysis means is then combined for further analysis. 
     In some embodiments, the proteomic analysis means comprises a mass spectroscopy method. In some instances, the mass spectroscopy method is a liquid-chromatography-mass spectrometry (LC-MS) method. In some cases, the proteomic analysis means further comprise analyzing the results from the mass spectroscopy method by an algorithm for protein identification. In some cases, the algorithm combines the results from the mass spectroscopy method with a protein sequence database for protein identification. In some cases, the algorithm comprises ProLuCID algorithm, Probity, Scaffold, SEQUEST, or Mascot. In some cases, the mass spectroscopy method is a MALDI-TOF based method. 
     In some embodiments, a value is assigned to each of the cysteine binding protein from the cysteine-reactive probe-protein complexes after proteomic analysis, in which the value is determined from the proteomic analysis. In some cases, the value assigned to each of the cysteine containing protein is obtained from a mass spectroscopy analysis. In some instances, the value is an area-under-the curve from a plot of signal intensity as a function of mass-to-charge ratio. In some embodiments, a first value is assigned to a cysteine binding protein from the first group of cysteine-reactive probe-protein complex of the first cell solution and a second value of the same cysteine binding protein from the second group of cysteine-reactive probe-protein complex of the second cell solution. In some instances, a ratio is then calculated between the two values, the first value and the second value, and assigned to the same cysteine binding protein. In some instances, a ratio of greater than 2 indicates that the cysteine binding protein is a candidate for interacting with the small molecule fragment. In some instances, the ratio is greater than 2.5, 3, 3.5, 4, 4.5, 5, 6, 7, 8, 9, or 10. In some cases, the ratio is at most 20. In some instances, the same small molecule fragment interacts with a number of cysteine binding proteins in the presence of a cysteine-reactive probe. In some instances, the small molecule modulates the interaction of a cysteine-reactive probe with its cysteine binding protein partners. In some instances, the spectrum of ratios for a small molecule fragment with its interacting protein partners in the presence of a cysteine-reactive probe indicates the specificity of the small molecule fragment toward the protein. In some instances, the spectrum of ratio indicates whether the small molecule fragment is a specific inhibitor to a protein or a pan inhibitor. 
     In some embodiments, the cysteine containing protein identified by the above method comprises a biologically active cysteine residue. In some instances, the biologically active cysteine site is a cysteine residue that is located about 10 Å or less to an active-site ligand or residue. In some cases, the cysteine residue that is located about 10 Å or less to the active-site ligand or residue is an active site cysteine. In some cases, the biologically active cysteine site is an active site cysteine. In some embodiments, the biologically active cysteine site is a cysteine residue that is located greater than 10 Å from an active-site ligand or residue. In some cases, the cysteine residue that is located greater than 10 Å from the active-site ligand or residue is a non-active site cysteine. In some instances, the biologically active cysteine site is a non-active site cysteine. 
     In some embodiments, the small molecule fragment that covalently interacts with the biologically active cysteine impairs and/or inhibits activity of the cysteine containing protein. In some instances, the cysteine containing protein exists in an active form. In some embodiments, the small molecule fragment and/or the cysteine-reactive probe interact with the active form of the cysteine containing protein. In some instances, the cysteine containing protein exists in a pro-active form. In some embodiments, the small molecule fragment and/or the cysteine-reactive probe interact with the pro-active form of the cysteine containing protein. 
     In some embodiments, the structural environment of the biologically active cysteine residue modulates the reactivity of the cysteine residue. In some embodiments, the structural environment is a hydrophobic environment or a hydrophilic environment. In some embodiments, the structural environment is a charged environment. In some embodiments, the structural environment is a nucleophilic environment. 
     In some embodiments, the cysteine containing protein is an enzyme, a transporter, a receptor, a channel protein, an adaptor protein, a chaperone, a signaling protein, a plasma protein, transcription related protein, translation related protein, mitochondrial protein, or cytoskeleton related protein. In some instances, the cysteine containing protein is an enzyme, a transporter, a receptor, a channel protein, an adaptor protein, a chaperone, a signaling protein, transcription related protein, or translation related protein. In some embodiments, the cysteine containing protein is a protein illustrated in Tables 1, 2, 3, 8 or 9. In some instances, the cysteine residue of the cysteine-containing proteins illustrated in Tables 1, 2, 3, 8 or 9 is denoted by (*) in Tables 1, 2, 3, 8 or 9. 
     In some instances, a set of cysteine-reactive probes are added to the cell solutions. For example, a first set of cysteine-reactive probes are added to the first cell solution and a second set of cysteine-reactive probes are added to the second cell solution. In some cases, each cysteine-reactive probe is different within the set. In some instances, the first set of cysteine-reactive probes is the same as the second set of cysteine-reactive probes. In some cases, the first set of cysteine-reactive probes generate a third group of cysteine-reactive probe-protein complexes and the second set of cysteine-reactive probes generate a fourth group of cysteine-reactive probe-protein complexes. In some instances, the set of cysteine-reactive probes further facilitates identification of cysteine containing proteins. 
     In some embodiments, the sample is a cell sample. In other instances, the sample is a tissue sample. 
     In some instances, the method is an in-situ method. 
     Small Molecule Fragments 
     In some embodiments, the small molecule fragments described herein comprise non-naturally occurring molecules. In some instances, the non-naturally occurring molecules do not include natural and/or non-natural peptide fragments, or small molecules that are produced naturally within the body of a mammal. 
     In some embodiments, the small molecule fragments described herein comprise a molecule weight of about 100 Dalton or higher. In some embodiments, the small molecule fragments comprise a molecule weight of about 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, 250, 260, 270, 280, 290, 300, 310, 320, 330, 340, 350, 360, 370, 380, 390, 400, 410, 420, 430, 440, 450, 500, 550, 600, 650, 700, 750, 800, 850, 900, 950, 1000 Dalton, or higher. In some instances, the molecule weight of the small molecule fragments are between about 150 and about 500, about 150 and about 450, abut 150 and about 440, about 150 and about 430, about 150 and about 400, about 150 and about 350, about 150 and about 300, about 150 and about 250, about 170 and about 500, about 180 and about 450, about 190 and about 400, about 200 and about 350, about 130 and about 300, or about 120 and about 250 Dalton. 
     In some embodiments, the molecule weight of the small molecule fragments described herein is the molecule weight prior to enrichment with one or more elements selected from a halogen, a nonmetal, a transition metal, or a combination thereof. In some embodiments, the molecule weight of the small molecule fragments described herein is the molecule weight prior to enrichment with a halogen. In some embodiments, the molecule weight of the small molecule fragments described herein is the molecule weight prior to enrichment with a nonmetal. In some embodiments, the molecule weight of the small molecule fragments described herein is the molecule weight prior to enrichment with a transition metal. In some embodiments, the molecular weight of the small molecule fragment is calculated based on carbon and hydrogen atoms and optionally further based on nitrogen, oxygen and/or sulfur atoms. 
     In some embodiments, the molecular weight of the small molecule fragment does not include the molecular weight of a halogen, a transition metal or a combination thereof. In some cases, the molecular weight of the small molecule fragment does not include the molecular weight of a halogen, the molecular weight of the small molecule fragment does not include the molecular weight of a transition metal. 
     In some embodiments, the small molecule fragments described herein comprise micromolar or millimolar binding affinity. In some instances, the small molecule fragments comprise a binding affinity of about 1 μM, 10 μM, 100 μM, 500 μM, 1 mM, 10 mM, or higher. 
     In some embodiments, the small molecule fragments described herein has a high ligand efficiency (LE). Ligand efficiency is the measurement of the binding energy per atom of a ligand to its binding partner. In some instances, the ligand efficiency is defined as the ratio of the Gibbs free energy (ΔG) to the number of non-hydrogen atoms of the compound (N): 
       LE=(Δ G )/ N.  
 
     In some cases, LE is also arranged as: 
       LE=1.4(−log IC 50 )/ N.  
 
     In some instances, the LE score is about 0.3 kcal mol −1  HA −1 , about 0.35 kcal mol −1  HA −1 , about 0.4 kcal mol −1  HA −1 , or higher. 
     In some embodiments, the small molecule fragments described herein are designed based on the Rule of 3. In some embodiments, the Rule of 3 comprises a non-polar solvent-polar solvent (e.g. octanol-water) partition coefficient log P of about 3 or less, a molecular mass of about 300 Daltons or less, about 3 hydrogen bond donors or less, about 3 hydrogen bond acceptors or less, and about 3 rotatable bonds or less. 
     In some embodiments, the small molecule fragments described herein comprises three cyclic rings or less. 
     In some embodiments, the small molecule fragments described herein binds to a cysteine residue of a polypeptide that is about 20 amino acid residues in length or more. In some instances, the small molecule fragments described herein binds to a cysteine residue of a polypeptide that is about 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 150, 200, 250, 300, 350, 400, 450, 500, 600, 700, 800, 900, 1000 amino acid residues in length or more. 
     In some embodiments, the small molecule fragments described herein further comprise pharmacokinctic parameters that are unsuitable as a therapeutic agent for administration without further optimization of the small molecule fragments. In some instances, the pharmacokinetic parameters that are suitable as a therapeutic agent comprise parameters in accordance with FDA guideline, or in accordance with a guideline from an equivalent Food and Drug Administration outside of the United States. In some instances, the pharmacokinetic parameters comprise the peak plasma concentration (C max), the lowest concentration of a therapeutic agent (C min), volume of distribution, time to reach C max, elimination half-life, clearance, and the life. In some embodiments, the pharmacokinetic parameters of the small molecule fragments are outside of the parameters set by the FDA guideline, or by an equivalent Food and Drug Administration outside of the United States. In some instances, a skilled artisan understands in view of the pharmacokinetic parameters of the small molecule fragments described herein that these small molecule fragments are unsuited as therapeutic agents without further optimization. 
     In some embodiments, the small molecule fragments described herein comprise a reactive moiety which forms a covalent interaction with the thiol group of a cysteine residue of a cysteine containing protein, and an affinity handle moiety. 
     In some instances, a small molecule fragment described herein is a small molecule fragment of Formula (I): 
     
       
         
         
             
             
         
       
     
     wherein:
         RM is a reactive moiety selected from a Michael acceptor moiety, a leaving group moiety, or a moiety capable of forming a covalent bond with the thiol group of a cysteine residue; and F is a small molecule fragment moiety.       

     In some instances, the Michael acceptor moiety comprises an alkene or an alkyne moiety. In some cases, F is obtained from a compound library. In some cases, the compound library comprises ChemBridge fragment library, Pyramid Platform Fragment-Based Drug Discovery, Maybridge fragment library, FRGx from AnalytiCon, TCI-Frag from AnCoreX, Bio Building Blocks from ASINEX, BioFocus 3D from Charles River, Fragments of Life (FOL) from Emerald Bio. Enamine Fragment Library, IOTA Diverse 1500, BIONET fragments library, Life Chemicals Fragments Collection, OTAVA fragment library, Prestwick fragment library, Selcia fragment library, TimTec fragment-based library, Allium from Vitas-M Laboratory, or Zenobia fragment library. 
     In some embodiments, the small molecule fragment of Formula (I) does not contain a second binding site. In some instances, the small molecule fragment moiety does not bind to the protein. In some cases, the small molecule fragment moiety does not covalently bind to the protein. In some instances, the small molecule fragment moiety does not interact with a secondary binding site on the protein. In some instances, the secondary binding site is an active site such as an ATP binding site. In some cases, the active site is at least about 10, 15, 20, 25, 35, 40 Å, or more away from the biologically active cysteine residue. In some instances, the small molecule fragment moiety does not interact with an active site such as an ATP binding site. 
     In some instances, F is a small molecule fragment moiety illustrated in  FIG. 3 . In some cases, F further comprises a linker moiety that connects F to the carbonyl moiety. In some cases, the small molecule fragment is a small molecule fragment illustrated in  FIG. 3 . 
     In some instances, F is a small molecule fragment moiety selected from: N-(4-bromophenyl)-N-phenylacrylamide, N-(1-benzoylpiperidin-4-yl)-2-chloro-N-phenylacetamide, 1-(4-benzylpiperidin-1-yl)-2-chloroethan-1-one, N-(2-(1H-indol-3-yl)ethyl)-2-chloroacetamide, N-(3,5-bis(trifluoromethyl)phenyl)acrylamide, N-(4-phenoxy-3-(trifluoromethyl)phenyl)-N-(pyridin-3-ylmethyl)acrylamide, N-(3,5-bis(trifluoromethyl)phenyl)acetamide, 2-chloro-1-(4-(hydroxydiphenylmethyl)piperidin-1-yl)ethan-1-one, (E)-3-(3,5-bis(trifluoromethyl)phenyl)-2-cyanoacrylamide, N-(3,5-bis(trifluoromethyl)phenyl)-2-bromopropanamide, N-(3,5-bis(trifluoromethyl)phenyl)-2-chloropropanamide, N-(3,5-bis(trifluoromethyl)phenyl)-N-(pyridin-3-ylmethyl)acrylamide, 3-(2-chloroacetamido)-5-(trifluoromethyl)benzoic acid, 1-(4-(5-fluorobenzisoxazol-3-yl)piperidin-1-yl)prop-2-en-1-one, tert-butyl 4-(4-acrylamido-2,6-difluorophenyl)piperazine-1-carboxylate, N-(4-bromo-2,5-dimethylphenyl)acrylamide, 2-Chloroacetamido-2-deoxy-α/β-D-glucopyranose, 2-chloro-1-(2-methyl-3,4-dihydroquinolin-1(2H)-yl)ethan-1-one, N-cyclohexyl-N-phenylacrylamide, 1-(5-bromoindolin-1-yl)prop-2-en-1-one, N-(1-benzylpiperidin-4-yl)-N-phenylacrylamide, 2-chloro-N-(2-methyl-5-(trifluoromethyl)phenyl)acetamide, 1-(5-bromoindolin-1-yl)-2-chloroethan-1-one, 2-chloro-N-(quinolin-5-yl)acetamide, 1-(4-benzylpiperidin-1-yl)prop-2-en-1-one, 2-chloro-N-((3-hydroxy-5-(hydroxymethyl)-2-methylpyridin-4-yl)methyl)acetamide, or 1-(6,7-dimethoxy-3,4-dihydroisoquinolin-2(1H)-yl)prop-2-en-1-one. 
     In some embodiments, the small molecule fragment of Formula (I) comprise a molecule weight of about 100, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, 250, 260, 270, 280, 290, 300, 310, 320, 330, 340, 350, 360, 370, 380, 390, 400, 410, 420, 430, 440, 450, 500, 550, 600, 650, 700, 750, 800, 850, 900, 950, 1000 Dalton, or higher. In some instances, the molecule weight of the small molecule fragment of Formula (I) is between about 150 and about 500, about 150 and about 450, abut 150 and about 440, about 150 and about 430, about 150 and about 400, about 150 and about 350, about 150 and about 300, about 150 and about 250, about 170 and about 500, about 180 and about 450, about 190 and about 400, about 200 and about 350, about 130 and about 300, or about 120 and about 250 Dalton. 
     In some embodiments, the molecule weight of the small molecule fragment of Formula (I) is the molecule weight prior to enrichment with one or more elements selected from a halogen, a nonmetal, a transition metal, or a combination thereof. In some embodiments, the molecule weight of the small molecule fragment of Formula (I) is the molecule weight prior to enrichment with a halogen. In some embodiments, the molecule weight of the small molecule fragment of Formula (I) is the molecule weight prior to enrichment with a nonmetal. In some embodiments, the molecule weight of the small molecule fragment of Formula (I) is the molecule weight prior to enrichment with a transition metal. 
     In some embodiments, the molecular weight of the small molecule fragment of Formula (I) does not include the molecular weight of a halogen, a transition metal or a combination thereof. In some embodiments, the molecular weight of the small molecule fragment of Formula (I) does not include the molecular weight of a halogen. In some embodiments, the molecular weight of the small molecule fragment of Formula (I) does not include the molecular weight of a transition metal. 
     In some instances, the small molecule fragment of Formula (I) comprises micromolar or millimolar binding affinity. In some instances, the small molecule fragment of Formula (I) comprises a binding affinity of about 1 μM, 10 μM, 100 μM, 500 μM, 1 mM, 10 mM, or higher. 
     In some cases, the small molecule fragment of Formula (I) has a LE score about 0.3 kcal mol −1  HA −1 , about 0.35 kcal mol −1  HA −1 , about 0.4 kcal mol −1  HA −1 , or higher 
     In some embodiments, the small molecule fragment of Formula (I) follows the design parameters of Rule of 3. In some instances, the small molecule fragment of Formula (I) has a non-polar solvent-polar solvent (e.g. octanol-water) partition coefficient log P of about 3 or less, a molecular mass of about 300 Daltons or less, about 3 hydrogen bond donors or less, about 3 hydrogen bond acceptors or less, and about 3 rotatable bonds or less. 
     In some embodiments, the small molecule fragment of Formula (I) comprises three cyclic rings or less. 
     In some embodiments, the small molecule fragment of Formula (I) binds to a cysteine residue of a polypeptide (e.g., a cysteine containing protein) that is about 20 amino acid residues in length or more. In some instances, the small molecule fragments described herein binds to a cysteine residue of a polypeptide (e.g., a cysteine containing protein) that is about 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 150, 200, 250, 300, 350, 400, 450, 500, 600, 700, 800, 900, 1000 amino acid residues in length or more. 
     In some instances, the small molecule fragment of Formula (I) has pharmacokinetic parameters outside of the parameters set by the FDA guideline, or by an equivalent Food and Drug Administration outside of the United States. In some instances, a skilled artisan understands in view of the pharmacokinetic parameters of the small molecule fragment of Formula (I) described herein that these small molecule fragment is unsuited as a therapeutic agent without further optimization. 
     In some embodiments, the small molecule fragment is a specific inhibitor or a pan inhibitor. 
     Cysteine-Reactive Probes 
     In some embodiments, a cysteine-reactive probe comprises a reactive moiety which forms a covalent interaction with the thiol group of a cysteine residue of a cysteine containing protein, and an affinity handle moiety. 
     In some embodiments, a cysteine-reactive probe is a cysteine-reactive probe of Formula (II): 
     
       
         
         
             
             
         
       
     
     wherein:
         RM is a reactive moiety selected from a Michael acceptor moiety, a leaving group moiety, or a moiety capable of forming a covalent bond to the thiol group of a cysteine residue; and AHM is an affinity handle moiety.       

     In some instances, the Michael acceptor moiety comprises an alkene or an alkyne moiety. In some cases, the affinity handle moiety comprises an affinity handle and a binding moiety that facilitates covalent interaction of the cysteine-reactive probe to a cysteine residue of a cysteine-containing protein. In some cases, the binding moiety is a small molecule fragment obtained from a compound library. In some instances, the compound library comprises ChemBridge fragment library, Pyramid Platform Fragment-Based Drug Discovery, Maybridge fragment library, FRGx from AnalytiCon. TCI-Frag from AnCoreX, Bio Building Blocks from ASINEX, BioFocus 3D from Charles River, Fragments of Life (FOL) from Emerald Bio, Enamine Fragment Library, IOTA Diverse 1500, BIONET fragments library, Life Chemicals Fragments Collection, OTAVA fragment library. Prestwick fragment library, Selcia fragment library, TimTec fragment-based library. Allium from Vitas-M Laboratory, or Zenobia fragment library. 
     In some embodiments, the affinity handle is a bioorthogonal affinity handle. In some embodiments, the affinity handle utilizes bioorthogonal chemistry. As used herein, bioorthogonal chemistry refers to any chemical reaction that occurs inside of a living system (e.g. a cell) without interfering with native biochemical processes. 
     In some cases, the affinity handle comprises a carbodiimide, N-hydroxysuccinimide (NHS) ester, imidoester, pentafluorophenyl ester, hydroxymethyl phosphine, maleimide, haloacetyl, pyridyl disulfide, thiosulfonate, vinylsulfone, hydrazide, alkoxyamine, alkyne, azide, or isocyanate group. In some cases, the affinity handle comprises an alkyne or an azide group. 
     In some instances, the affinity handle is an alkyne group. The term “alkyne group” as used in the context of an affinity handle refers to a group with a chemical formula of H—C≡C—R, HC 2 R, R 1 —C≡C—R 2 , or R 1 C 2 R 2 . In the context of the present chemical formula, R, R 1 , and R 2  are independently a cysteine-reactive probe portion described herein, a linker, or a combination thereof. In some cases, the alkyne group is capable of being covalently linked in a chemical reaction with a molecule containing an azide. In some instances, the affinity handle is an azide group. 
     In some instances, the affinity handle (e.g. alkyne group or azide group) serve as nonnative and non-perturbed bioorthogonal chemical handles. In some instances, the affinity handle (e.g. alkyne group or azide group) is further derivatized through chemical reactions such as click chemistry. In some instances, the click chemistry is a copper(I)-catalyzed [3+2]-Huisgen 1,3-dipolar cyclo-addition of alkynes and azides leading to 1,2,3-triazoles. In other instances, the click chemistry is a copper free variant of the above reaction. 
     In some instances, the affinity handle further comprises a linker. In some instances, the linker bridges the affinity handle to the reactive moiety. 
     In some instances, the affinity handle is further conjugated to an affinity ligand. In some cases, the affinity ligand comprises a chromophore, a labeling group, or a combination thereof. In some embodiments, the chromophore comprises fluorochrome, non-fluorochrome chromophore, quencher, an absorption chromophore, fluorophore, organic dye, inorganic dye, metal chelate, or a fluorescent enzyme substrate. In some cases, the chromophore comprises non-fluorochrome chromophore, quencher, an absorption chromophore, fluorophore, organic dye, inorganic dye, metal chelate, or a fluorescent enzyme substrate. In other cases, the chromophore comprises a fluorophore. 
     In some embodiments, the fluorophore comprises rhodamine, rhodol, fluorescein, thiofluorescein, aminofluorescein, carboxyfluorescein, chlorofluorescein, methylfluorescein, sulfofluorescein, aminorhodol, carboxythodol, chlororhodol, methylrhodol, sulforhodol, aminorhodamine, carboxyrhodamine, chlororhodamine, mcthylrhodamine, sulforhodamine, thiorhodamine, cyanine, indocarbocyanine, oxacarbocyvanine, thiacarbocyanine, merocyanine, cyanine 2, cyanine 3, cyanine 3.5, cyanine 5, cyanine 5.5, cyanine 7, oxadiazole derivatives, pyridyloxazole, nitrobenzoxadiazole, benzoxadiazole, pyren derivatives, cascade blue, oxazine derivatives. Nile red, Nile blue, cresyl violet, oxazine 170, acridine derivatives, proflavin, acridine orange, acridine yellow, arylmethine derivatives, auramine, crystal violet, malachite green, tetrapyrrole derivatives, porphin, phtalocyanine, bilirubin 1-dimethylaminonaphthyl-5-sulfonate, 1-anilino-8-naphthalene sulfonate, 2-p-touidinyl-6-naphthalene sulfonate, 3-phenyl-7-isocyanatocoumarin, N-(p-(2-benzoxazolyl)phenyl)maleimide, stilbenes, pyrenes, 6-FAM (Fluorescein), 6-FAM (NHS Ester), 5(6)-FAM, 5-FAM, Fluorescein dT, 5-TAMRA-cadavarine, 2-aminoacridone, HEX, JOE (NHS Ester), MAX, TET, ROX, TAMRA, TARMA™ (NHS Ester), TEX 615, ATTO™ 488, ATTO™ 532, ATTO™ 550, ATTO™ 565. ATTO™ Rho101, ATTO™ 590, ATTO™ 633, ATTO™ 647N, TYE™ 563, TYE™ 665, or TYE™ 705. 
     In some embodiments, the labeling group is a biotin moiety, a streptavidin moiety, bead, resin, a solid support, or a combination thereof. As used herein, a biotin moiety described herein comprises biotin and biotin derivatives. Exemplary biotin derivatives include, but are not limited by, desthiobiotin, biotin alkyne or biotin azide. In some instances, a biotin moiety described herein is desthiobiotin. In some cases, a biotin moiety described herein is d-Desthiobiotin. 
     In some instances, the labeling group is a biotin moiety. In some instances, the biotin moiety further comprises a linker such as a 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 or more residues in length. In some instances, the linker further comprises a cleavage site, such as a protease cleavage site. In some cases, the biotin moiety interacts with a streptavidin moiety. In some instances, the biotin moiety is further attached to a bead, such as a streptavidin-coupled bead. In some instances, the biotin moiety is further attached to a resin or a solid support, such as a streptavidin-coupled resin or a streptavidin-coupled solid support. In some instances, the solid support is a plate, a platform, a cover slide, a microfluidic channel, and the like. 
     In some embodiments, the affinity handle moiety further comprises a chromophore. 
     In some embodiments, the cysteine-reactive probe is a cysteine-reactive probe illustrated in  FIG. 3 . In some embodiments, the cysteine-reactive probe is a cysteine-reactive probe selected from: N-(hex-5-yn-1-yl)-2-iodoacetamide, lodoacetamide-rhodamine, 3-acrylamido-N-(hex-5-yn-1-yl)-5-(trifluoromethyl)benzamide, 3-acrylamido-N-(hex-5-yn-1-yl)-5-(trifluoromethyl)benzamide, or 2-chloro-N-(1-(3-ethynylbenzoyl)piperidin-4-yl)-N-phenylacetamide. 
     Cysteine Containing Proteins 
     In some instances, the cysteine containing protein is a soluble protein or a membrane protein. In some instances, the cysteine containing protein is involved in one or more of a biological process such as protein transport, lipid metabolism, apoptosis, transcription, electron transport, mRNA processing, or host-virus interaction. In some instances, the cysteine containing protein is associated with one or more of diseases such as cancer or one or more disorders or conditions such as immune, metabolic, developmental, reproductive, neurological, psychiatric, renal, cardiovascular, or hematological disorders or conditions. 
     In some embodiments, the cysteine containing protein comprises a biologically active cysteine residue. In some embodiments, the cysteine containing protein comprises one or more cysteines in which at least one cysteine is a biologically active cysteine residue. In some cases, the biologically active cysteine site is a cysteine residue that is located about 10 Å or less to an active-site ligand or residue. In some cases, the cysteine residue that is located about 10 Å or less to the active-site ligand or residue is an active site cysteine. In other cases, the biologically active cysteine site is a cysteine residue that is located greater than 10 Å from an active-site ligand or residue. In some instances, the cysteine residue is located greater than 12 Å, 15 Å, 20 Å, 25 Å, 30 Å, 35 Å, 40 Å, 45 Å, or greater than 50 Å from an active-site ligand or residue. In some cases, the cysteine residue that is located greater than 10 Å from the active-site ligand or residue is a non-active site cysteine. In additional cases, the cysteine containing protein exists in an active form, or in a pro-active form. 
     In some embodiments, the cysteine containing protein comprises one or more functions of an enzyme, a transporter, a receptor, a channel protein, an adaptor protein, a chaperone, a signaling protein, a plasma protein, transcription related protein, translation related protein, mitochondrial protein, or cvtoskeleton related protein. In some embodiments, the cysteine containing protein is an enzyme, a transporter, a receptor, a channel protein, an adaptor protein, a chaperone, a signaling protein, a plasma protein, transcription related protein, translation related protein, mitochondrial protein, or cytoskeleton related protein. In some instances, the cysteine containing protein has an uncategorized function. 
     In some embodiments, the cysteine containing protein is an enzyme. An enzyme is a protein molecule that accelerates or catalyzes chemical reaction. In some embodiments, non-limiting examples of enzymes include kinases, proteases, or deubiquitinating enzymes. 
     In some instances, exemplary kinases include tyrosine kinases such as the TEC family of kinases such as Tec, Bruton&#39;s tvrosine kinase (Btk), interleukin-2-indicible T-cell kinase (Itk) (or Emt/Tsk). Bmx. and Txk/Rlk; spleen tyrosine kinase (Syk) family such as SYK and Zeta-chain-associated protein kinase 70 (ZAP-70); Src kinases such as Src, Yes, Fyn, Fgr, Lck, Hck. Blk, Lyn, and Frk; JAK kinases such as Janus kinase 1 (JAK1), Janus kinase 2 (JAK2), Janus kinase 3 (JAK3), and Tyrosine kinase 2 (TYK2); or ErbB family of kinases such as Her1 (EGFR, ErbB1), Her2 (Neu. ErbB2), Her3 (ErbB3), and Her4 (ErbB4). 
     In some embodiments, the cysteine containing protein is a protease. In some embodiments, the protease is a cysteine protease. In some cases, the cysteine protease is a caspase. In some instances, the caspase is an initiator (apical) caspase. In some instances, the caspase is an effector (executioner) caspase. Exemplary caspase includes CASP2, CASP8, CASP9, CASP10, CASP3, CASP6, CASP7, CASP4, and CASP5. In some instances, the cysteine protease is a cathepsin. Exemplary cathepsin includes Cathepsin B, Cathepsin C, CathepsinF, Cathepsin H, Cathepsin K, Cathepsin L1, Cathepsin L2, Cathepsin O. Cathepsin S, Cathepsin W, or Cathepsin Z. 
     In some embodiments, the cysteine containing protein is a deubiquitinating enzyme (DUB). In some embodiments, exemplary deubiquitinating enzymes include cysteine proteases DUBs or metalloproteases. Exemplary cysteine protease DUBs include ubiquitin-specific protease (USP/UBP) such as USP1, USP2, USP3, USP4, USP5, USP6, USP7, USP8, USP9X, USP9Y, USP10, USP11, USP12, USP13, USP14, USP15, USP16, USP17, USP17L2, USP17L3, USP17L4, USP17L5, USP17L7, USP17L8, USP18, USP19, USP20, USP21. USP22, USP23, USP24, USP25, USP26, USP27X, USP28. USP29, USP30, USP31, USP32, USP33, USP34, USP35. USP36, USP37, USP38, USP39, USP40, USP41, USP42, USP43, USP44, USP45, or USP46; ovarian tumor (OTU) proteases such as OTUB1 and OTUB2; Machado-Josephin domain (MJD) proteases such as ATXN3 and ATXN3L; and ubiquitin C-terminal hydrolase (UCH) proteases such as BAP1, UCHL1, UCHL3, and UCHL5. Exemplary metalloproteases include the Jab1/Mov34/Mpr1 Pad1 N-terminal+(MPN+) (JAMM) domain proteases. 
     In some embodiments, exemplary cysteine containing proteins as enzymes include, but are not limited to, Glyceraldehyde-3-phosphate dehydrogenase (GAPDH), Protein arginine N-methyltransferase 1 (PRMT1), Peptidyl-prolyl cis-trans isomerase NIMA-interaction (PIN1), Acetyl-CoA acetyltransferase (mitochondrial) (ACAT1). Glutathione S-transferase P (GSTP1). Elongation factor 2 (EEF2). Glutathione S-transferase omega-1 (GSTO1), Acetyl-CoA acetyltransferase (mitochondrial) (ACAT1), Protein disulfide-isomerase A4 (PDIA4), Prostaglandin E synthase 3 (PTGES3), Adenosine kinase (ADK), Elongation factor 2 (EEF2), Isoamyl acetate-hydrolyzing esterase 1 homolog (IAHI), Peroxiredoxin-5 (mitochondrial) (PRDX5), Inosine-5-monophosphate dehydrogenase 2 (IMPDH2), 3-hydroxyacyl-CoA dehydrogenase type-2 (HSD17B10), Omega-amidase NIT2 (NIT2), Aldose reductase (AKR1B1), Monofunctional C1-tetrahydrofolate synthase (mitochondrial) (MTHFD1L), Protein disulfide-isomerase A6 (PDIA6), Pyruvate kinase isozymes M1/M2 (PKM), 6-phosphogluconolactonase (PGLS), Acetl-CoA acetyltransferase (mitochondrial) (ACAT1), ERO1-like protein alpha (EROIL), Thioredoxin domain-containing protein 17 (TXNDC17), Protein disulfide-isomerase A4 (PDIA4), Protein disulfide-isomerase A3 (PDIA3), 3-ketoacvl-CoA thiolase (mitochondrial) (ACAA2), Dynamin-2 (DNM2), DNA replication licensing factor MCM3 (MCM3), Serine-tRNA ligase (cytoplasmic) (SARS), Fatty acid synthase (FASN), Acetyl-CoA acetyltransferase (mitochondrial) (ACAT1), Protein disulfide-isomerase (P4HB), Deoxycytidine kinase (DCK), Eukaryotic translation initiation factor 3 subunit (EIF3F), Protein disulfide-isomerase A6 (PDIA6), UDP-N-acetylglucosamine-peptide N-acetylglucosamine (OGT), Ketosamine-3-kinase (FN3KRP), Protein DJ-1 (PARK7), Phosphoglycolate phosphatase (PGP), DNA replication licensing factor MCM6 (MCM6), Fructose-2,6-bisphosphatase TIGAR (TIGAR), Cleavage and polyadenylation specificity factor subunit (CPSF3), Ubiquitin-conjugating enzyme E2 L3 (UBE2L3), Alanine-tRNA ligase, cytoplasmic (AARS), Mannose-1-phosphate guanyltransferase alpha (GMPPA), C-1-tetrahydrofolate synthase (cytoplasmic) (MTHFD1), Dynamin-1-like protein (DNM1L), Protein disulfide-isomerase A3 (PDIA3), Aspartyl aminopeptidase (DNPEP), Acetyl-CoA acetyltransferase (cytosolic) (ACAT2), Thioredoxin domain-containing protein 5 (TXNDC5), Thymidine kinase (cytosolic) (TK1), Inosine-5-monophosphate dehydrogenase 2 (IMPDH2), Ubiquitin carboxyl-terminal hydrolase isozyme L3 (UCHL3), Integrin-linked protein kinase (ILK), Cyclin-dependent kinase 2 (CDK2), Histone acetyltransferase type B catalytic subunit (HAT1), Enoyl-CoA delta isomerase 2 (mitochondrial) (ECI2), C-1-tetrahydrofolate synthase (cytoplasmic) (MTHFD1), Deoxycytidine kinase (DCK), Ubiquitin-like modifier-activating enzyme 6 (UBA6), Protein-L-isoaspartate(D-aspartate)O-methyltransferase (PCMTI), Monofunctional C1-tetrahydrofolate synthase (mitochondrial) (MTHFD1L), Thymidylate kinase (DTYMK), Protein ETHE (mitochondrial) (ETHE 1), Arginine-tRNA ligase (cvtoplasmic) (RARS), NEDD8-activating enzyme E1 catalytic subunit (UBA3), Dual specificity mitogen-activated protein kinase (MAP2K3). Ubiquitin-conjugating enzyme E2S (UBE2S), Amidophosphoribosyltransferase (PPAT), Succinate-semialdehyde dehydrogenase (mitochondrial) (ALDH5A1), CAD, Phosphoenolpyruvate carboxykinase (PCK2), 6-phosphofructokinase type C (PFKP), Acyl-CoA synthetase family member 2 (mitochondrial) (ACSF2), Multifunctional protein ADE2 (PAICS), Desumoylating isopeptidase 1 (DESI1), 6-phosphofructokinase type C (PFKP), V-type proton ATPasc catalytic subunit A (ATP6V1A), 3-ketoacyl-CoA thiolase (peroxisomal) (ACAA1), Galactokinase (GALK1), Thymidine kinase (cytosolic) (TK1), ATPase WRNIP1 (WRNIP1), Phosphoribosylformylglycinamidine synthase (PFAS), V-type proton ATPase catalytic subunit A (ATP6V1A), Thioredoxin domain-containing protein 5 (TXNDC5), 4-trimethylaminobutyraldehyde dehydrogenase (ALDH9A1). Dual specificity mitogen-activated protein kinase (MAP2K4), Calcineurin-like phosphoesterase domain-containing (CPPED1), Dual specificity protein phosphatase 12 (DUSP12), Phosphoribosylformylglycinamidine synthase (PFAS), Diphosphomevalonate decarboxylase (MVD), D-3-phosphoglycerate dehydrogenase (PHGDH), Cell cycle checkpoint control protein RAD9A (RAD9A), Peroxiredoxin-1 (PRDX1), Sorbitol dehydrogenase (SORD), Pcroxiredoxin-4 (PRDX4), AMP deaminase 2 (AMPD2), Isocitrate dehydrogenase (IDH1), Pyruvate carboxvlase (mitochondrial) (PC), Integrin-linked kinase-associated serine/threonine (ILKAP), Methylmalonate-semialdehyde dehydrogenase (ALDH6A1), 26S proteasome non-ATPase regulatory subunit 14 (PSMD 14), Thymidylate kinase (DTYMK), 6-phosphofructo-2-kinase/fructose-2,6-bisphosphata (PFKFB2). Peroxiredoxin-5 (mitochondrial) (PRDX5), PDP1, Cathepsin B (CTSB), Transmembrane protease serine 12 (TMPRSS 12), UDP-glucose 6-dehydrogenase (UGDH), Histidine triad nucleotide-binding protein 1 (HINT1), E3 ubiquitin-protein ligase UBR5L (UBRL5), SAM domain and HD domain-containing protein 1 (SAMHD1), Probable tRNA threonylcarbamovyladenosine biosynthesis (OSGEP), Methylated-DNA-protein-cysteine methyltransferase (MGMT). Fatty acid synthase (FASN), Adenosine deaminase (ADA), Cyclin-dependent kinase 19 (CDK19), Serine/threonine-protein kinase 38 (STK38), Mitogen-activated protein kinase 9 (MAPK9), tRNA (adenine(58)-N(1))-methyltransferase catalytic (TRMT61A), Glyoxylate reductase/hydroxypyruvate reductase (GRHPR), Aldehyde dehydrogenase (mitochondrial) (ALDH2), Mitochondrial-processing peptidase subunit beta (PMPCB), 3-ketoacyl-CoA thiolase, peroxisomal (ACAA1), Lysophosphatidic acid phosphatase type 6 (ACP6), Ubiquitin/ISG15-conjugating enzyme E2 L6 (UBE2L6), Caspase-8 (CASP8), 2,5-phosphodiesterase 12 (PDE12), Thioredoxin domain-containing protein 12 (TXNDC12), Nitrilase homolog 1 (NIT1). ERO1-like protein alpha (ERO1L), SUMO-activating enzyme subunit 1 (SAE1), Leucine-tRNA ligase (cytoplasmic) (LARS), Protein-glutamine gamma-glutamyltransferase 2 (TGM2), Probable DNA dC-dU-editing enzyme APOBEC-3C (APOBEC3C), Double-stranded RNA-specific adenosine deaminase (ADAR), Isocitrate dehydrogenase (IDH2), Methylcrotonoyl-CoA carboxylase beta chain (mitochondrial) (MCCC2). Uridine phosphorylase 1 (UPP1). Glycogen phosphorylase (brain form) (PYGB), E3 ubiquitin-protein ligase UBR5 (UBR5). Procollagen-lysine,2-oxoglutarate 5-dioxygenase 1 (PLOD1), Ubiquitin carboxyl-terminal hydrolase 48 (USP48), Aconitate hydratase (mitochondrial) (ACO2), GMP reductase 2 (GMPR2), Pyrroline-5-carboxylate reductase 1 (mitochondrial) (PYCR1), Cathepsin Z (CTSZ), E3 ubiquitin-protein ligase UBR2 (UBR2), Cysteine protease ATG4B (ATG4B), Serine/threonine-protein kinase Nek9 (NEK9), Lysine-specific demethylase 4B (KDM4B), Insulin-degrading enzyme (IDE), Dipeptidyl peptidase 9 (DPP9), Decaprenyl-diphosphate synthase subunit 2 (PDSS2), TFIIH basal transcription factor complex helicase (ERCC3). Methionine-R-sulfoxide reductase B2 (mitochondrial) (MSRB2), E3 ubiquitin-protein ligase BREIB (RNF40), Thymidylate synthase (TYMS), Cyclin-dependent kinase 5 (CDK5), Bifunctional 3-phosphoadenosine 5-phosphosulfate (PAPSS2), Short/branched chain specific acyl-CoA dehydrogenase (ACADSB), Cathepsin D (CTSD), E3 ubiquitin-protein ligase HUWE1 (HUWE1), Calpain-2 catalytic subunit (CAPN2), Dual specificity mitogen-activated protein kinase (MAP2K7), Mitogen-activated protein kinase kinase kinase MLT (MLTK), Bleomycin hydrolase (BLMH), Probable ATP-dependent RNA helicase DDX59 (DDX59), Cystathionine gamma-lyase (CTH). S-adenosylmethionine synthase isoform type-2 (MAT2A), 6-phosphofructokinase type C (PFKP), Cvtidine deaminase (CDA). DNA-directed RNA polymerase II subunit RPB2 (POLR2B), Protein disulfide-isomerase (P4HB), Procollagen-lysine,2-oxoglutarate 5-dioxygenase 3 (PLOD3), Nucleoside diphosphate-linked moiety X motif 8 (mitochondrial) (NUDT8), E3 ubiquitin-protein ligase HUWE1 (HUWE1). Methylated-DNA-protein-cysteine methyltransferase (MGMT), Nitrilase homolog 1 (NIT1), Interferon regulatory factor 2-binding protein 1 (IRF2BP1), Ubiquitin carboxyl-terminal hydrolase 16 (USP16), Glycylpeptide N-tetradecanoyltransferase 2 (NMT2), Cyclin-dependent kinase inhibitor 3 (CDKN3). Hydroxysteroid dehydrogenase-like protein 2 (HSDL2), Serine/threonine-protein kinase VRK1 (VRK1). Serine/threonine-protein kinase A-Raf (ARAF), ATP-citrate synthase (ACLY), Probable ribonuclease ZC3H12D (ZC3H12D), Peripheral plasma membrane protein CASK (CASK), DNA polymerase epsilon subunit 3 (POLE3), Aldehyde dehydrogenase X (mitochondrial) (ALDHIB1), UDP-N-acetylglucosamine transferase subunit ALG13 (ALG13), Protein disulfide-isomerase A4 (PDIA4), DNA polymerase alpha catalytic subunit (POLA1), Ethylmalonyl-CoA decarboxylase (ECHDC1), Protein-tyrosine kinase 2-beta (PTK2B), E3 SUMO-protein ligase RanBP2 (RANBP2), Legumain (LGMN), Non-specific lipid-transfer protein (SCP2), Long-chain-fatty-acid-CoA ligase 4 (ACSL4), Dual specificity protein phosphatase 12 (DUSP12), Oxidoreductase HTATIP2 (HTATIP2), Serine/threonine-protein kinase MRCK beta (CDC42BPB). Histone-lysine N-methyltransferase EZH2 (EZH2), Non-specific lipid-transfer protein (SCP2), Dual specificity mitogen-activated protein kinase (MAP2K7), Ubiquitin carboxyl-terminal hydrolase 28 (USP28), 6-phosphofructokinase (liver type) (PFKL), SWI/SNF-related matrix-associated actin-dependent (SMARCAD1), Protein phosphatase methylesterase 1 (PPME1). DNA replication licensing factor MCM5 (MCM5), 6-phosphofructo-2-kinase/fructose-2,6-bisphosphata (PFKFB4), Dehydrogenase/reductase SDR family member 11 (DHRS11), Pyroglutamyl-peptidase 1 (PGPEP1), Probable E3 ubiquitin-protein ligase (MYCBP2), DNA fragmentation factor subunit beta (DFFB), Deubiquitinating protein VCIP135 (VCPIP1), Putative transferase CAF17 (mitochondrial) (IBA57), Calpain-7 (CAPN7), GDP-L-fucose synthase (TSTA3), Protein disulfide-isomerase A4 (PDIA4, Probable ATP-dependent RNA helicase (DDX59), RNA exonuclease 4 (REXO4), PDKI, E3 SUMO-protein ligase (PIAS4), DNA (cytosine-5)-methyltransferase 1 (DNMT1), Alpha-aminoadipic semialdehyde dehydrogenase (ALDH7A), Hydroxymethylglutaryl-CoA synthase (cytoplasmic) (HMGCS 1), E3 ubiquitin-protein ligase (SMURF2), Aldehyde dehydrogenase X (mitochondrial) (ALDHIB1), Tvrosine-protein kinase (BTK), DNA repair protein RAD50 (RAD50), ATP-binding domain-containing protein 4 (ATPBD4), Nucleoside diphosphate kinase 3 (NME3), Interleukin-1 receptor-associated kinase 1 (IRAK1), Ribonuclease P/MRP protein subunit POP5 (POP5), Peptide-N(4)-(N-acetyl-beta-glucosaminyl)asparagin (NGLY 1), Caspase-2 (CASP2), Ribosomal protein S6 kinase alpha-3 (RPS6KA3), E3 ubiquitin-protein ligase UBR1 (UBR1), Serine/threonine-protein kinase Chk2 (CHEK2), Phosphatidylinositol 3,4,5-trisphosphate 5-phospha (INPPL 1), Histone acetvltransferase p300 (EP300), Creatine kinase U-type (mitochondrial) (CKMTIB), E3 ubiquitin-protein ligase TRIM33 (TRIM33), Cancer-related nucleoside-triphosphatase (NTPCR), Aconitate hydratase (mitochondrial) (ACO2), Ubiquitin carboxyl-terminal hydrolase 34 (USP34), Probable E3 ubiquitin-protein ligase HERC4 (HERC4), E3 ubiquitin-protein ligase HECTD1 (HECTD1), Peroxisomal 2,4-dienoyl-CoA reductase (DECR2), Helicase ARIP4 (RAD54L2). Ubiquitin-like modifier-activating enzyme 7 (UBA7), ER degradation-enhancing alpha-mannosidase-like 3 (EDEM3). Ubiquitin-conjugating enzyme E20 (UBE2O). Dual specificity mitogen-activated protein kinase (MAP2K7), Myotubularin-related protein 1 (MTMR1), Calcium-dependent phospholipase A2 (PLA2G5), Mitotic checkpoint serine/threonine-protein kinase (BUB1B). Putative transferase CAF17 (mitochondrial) (IBA57), Tyrosine-protein kinase ZAP-70 (ZAP70). E3 ubiquitin-protein ligase pellino homolog 1 (PELI1), Neuropathy target esterase (PNPLA6), Ribosomal protein S6 kinase alpha-3 (RPS6KA3), N6-adenosine-methyltransferase 70 kDa subunit (METTL3), Fructosamine-3-kinase (FN3K), Ubiquitin carboxyl-terminal hydrolase 22 (USP22), Rab3 GTPase-activating protein catalytic subunit (RAB3GAP1), Caspase-5 (CASP5), L-2-hydroxyglutarate dehydrogenase (mitochondrial) (L2HGDH), Saccharopine dehydrogenase-like oxidoreductase (SCCPDH), FLAD1 FAD synthase, Lysine-specific demethylase 3A (KDM3A), or Ubiquitin carboxyl-terminal hydrolase 34 (USP34). 
     In some embodiments, the cysteine containing protein is a signaling protein. In some instances, exemplary signaling protein includes vascular endothelial growth factor (VEGF) proteins or proteins involved in redox signaling. Exemplary VEGF proteins include VEGF-A, VEGF-B, VEGF-C, VEGF-D. and PGF. Exemplary proteins involved in redox signaling include redox-regulatory protein FAM213A. 
     In some embodiments, the cysteine containing protein is a transcription factor or regulator. Exemplary cysteine containing proteins as transcription factors and regulators include, but are not limited to, 40S ribosomal protein S3 (RPS3). Basic leucine zipper and W2 domain-containing protein (BZW1). Poly(rC)-binding protein 1 (PCBP1), 40S ribosomal protein S11 (RPS11), 40S ribosomal protein S4, X isoform (RPS4X), Signal recognition particle 9 kDa protein (SRP9), Non-POU domain-containing octamer-binding protein (NONO), N-alpha-acetyltransferase 15, NatA auxiliary subunit (NAA15), Cleavage stimulation factor subunit 2 (CSTF2), Lamina-associated polypeptide 2, isoform alpha (TMPO), Heterogeneous nuclear ribonucleoprotein R (HNRNPR), MMS19 nucleotide excision repair protein homolog (MMS19), SWI/SNF complex subunit SMARCC2 (SMARCC2), Enhancer of mRNA-decapping protein 3 (EDC3), H/ACA ribonucleoprotein complex subunit 2 (NHP2), WW domain-containing adapter protein with coiled-c (WAC), N-alpha-acetyltransferase 15 NatA auxiliary subunit (NAA15), 40S ribosomal protein S11 (RPS11), Signal transducer and activator of transcription 1 (STAT1), Mediator of RNA polymerase II transcription subunit (MED15), Lamina-associated polypeptide 2 (isoform alpha) (TMPO), MMS19 nucleotide excision repair protein homolog (MMS19), DNA mismatch repair protein Msh2 (MSH2). Recombining binding protein suppressor of hairless (RBPJ). Mediator of RNA polymerase II transcription subunit (MED17), Heterogeneous nuclear ribonucleoprotein U (HNRNPU), Transcription initiation factor IIA subunit 2 (GTF2A2), Chromatin accessibility complex protein 1 (CHRAC1), CDKN2A-interacting protein (CDKN2AIP). Zinc finger protein 217 (ZNF217), Signal transducer and activator of transcription 3 (STAT3), WD repeat and HMG-box DNA-binding protein 1 (WDHDI), Lamina-associated polypeptide 2 (isoform alpha) (TMPO), Lamina-associated polypeptide 2 (isoforms beta/gam) (TMPO), Interferon regulatory factor 4 (IRF4), Protein flightless-1 homolog (FLII), Heterogeneous nuclear ribonucleoprotein F (HNRNPF). Nucleus accumbens-associated protein 1 (NACC1), Transcription elongation regulator 1 (TCERG1), Protein HEXIM1 (HEXIM1). Enhancer of mRNA-decapping protein (EDC3), Zinc finger protein Aiolos (IKZF3), Transcription elongation factor SPT5 (SUPT5H), Forkhead box protein K1 (FOXK1), LIM domain-containing protein 1 (LIMD1), MMS19 nucleotide excision repair protein homolog (MMS19), Elongator complex protein 4 (ELP4). Ankyrin repeat and KH domain-containing protein 1 (ANKHD1), PML, Nuclear factor NF-kappa-B p100 subunit (NFKB2), Heterogeneous nuclear ribonucleoprotein L-like (HNRPLL), CCR4-NOT transcription complex subunit 3 (CNOT3), Constitutive coactivator of PPAR-gamma-like protein (FAM120A), Mediator of RNA polymerase II transcription subunit (MED15), 60S ribosomal protein L7 (RPL7), Interferon regulatory factor 8 (IRF8), COUP transcription factor 2 (NR2F2), Mediator of RNA polymerase II transcription subunit (MED1), tRNA (uracil-5-)-mcthyltransferase homolog A (TRMT2A), Transcription factor p65 (RELA), Exosome complex component RRP42 (EXOSC7), General transcription factor 3C polypeptide 1 (GTF3C1), Mothers against decapentaplegic homolog 2 (SMAD2), Ankyrin repeat domain-containing protein 17 (ANKRDI7), MMSl9 nucleotide excision repair protein homolog (MMS19), Death domain-associated protein 6 (DAXX), Zinc finger protein 318 (ZNF318), Thioredoxin-interacting protein (TXNIP), Glucocorticoid receptor (NR3C1), Iron-responsive element-binding protein 2 (IREB2), Zinc finger protein 295 (ZNF295). Polycomb protein SUZ12 (SUZ12), Cleavage stimulation factor subunit 2 tau variant (CSTF2T), C-myc promoter-binding protein (DENND4A), Pinin (PNN), Mediator of RNA polymerase II transcription subunit (MED9), POU domain, class 2, transcription factor 2 (POU2F2), Enhancer of mRNA-decapping protein 3 (EDC3), A-kinase anchor protein 1 (mitochondrial) (AKAP), Transcription factor RelB (RELB), RNA polymerase II-associated protein 1 (RPAP 1), Zinc finger protein 346 (ZNF346), Chromosome-associated kinesin KIF4A (KIF4A), Mediator of RNA polymerase II transcription subunit (MED12), Protein NPAT (NPAT), Leucine-rich PPR motif-containing protein (mitochondrial) (LRPPRC), AT-hook DNA-binding motif-containing protein 1 (AHDC1), Mediator of RNA polymerase II transcription subunit (MED12), Bromodomain-containing protein 8 (BRD8), Trinucleotide repeat-containing gene 6B protein (TNRC6B), Aryl hydrocarbon receptor nuclear translocator (ARNT), Activating transcription factor 7-interacting protein (ATF71P), Glucocorticoid receptor (NR3C1), Chromosome transmission fidelity protein 18 homolog (CHTF18), or C-myc promoter-binding protein (DENND4A). 
     In some embodiments, the cysteine containing protein is a channel, transporter or receptor. Exemplary cysteine containing proteins as channels, transporters, or receptors include, but are not limited to, Chloride intracellular channel protein 4 (CLIC4), Exportin-1 (XPO1), Thioredoxin (TXN), Protein SEC13 homolog (SEC13), Chloride intracellular channel protein 1 (CLIC1), Guanine nucleotide-binding protein subunit beta-2 (GNB2L1), Sorting nexin-6 (SNX6), Conserved oligomeric Golgi complex subunit 3 (COG3), Nuclear cap-binding protein subunit 1 (NCBP1), Cytoplasmic dynein 1 light intermediate chain 1 (DYNCILI1), MOB-like protein phocein (MOB4). Programmed cell death 6-interacting protein (PDCD6IP), Glutaredoxin-1 (GLRX), ATP synthase subunit alpha (mitochondrial) (ATP5A1), Treacle protein (TCOF1), Dynactin subunit 1 (DCTN1), Importin-7 (IPO7), Exportin-2 (CSE1L), ATP synthase subunit gamma (mitochondrial) (ATP5C1), Trafficking protein particle complex subunit 5 (TRAPPC5), Thioredoxin mitochondrial (TXN2), THO complex subunit 6 homolog (THOC6), Exportin-1 (XPO), Nuclear pore complex protein Nup50 (NUP50), Treacle protein (TCOF1), Nuclear pore complex protein Nup93 (NUP93), Nuclear pore glycoprotein p62 (NUP62), Cytoplasmic dynein 1 heavy chain 1 (DYNC1H1), Thioredoxin-like protein 1 (TXNL1), Nuclear pore complex protein Nup214 (NUP214). Protein lin-7 homolog C (LIN7C), ADP-ribosylation factor-binding protein GGA2 (GGA2), Trafficking protein particle complex subunit 4 (TRAPPC4), Protein quaking (QKI), Perilipin-3 (PLIN3), Copper transport protein ATOX1 (ATOX1), Unconventional myosin-Ic (MYO IC), Nucleoporin NUP53 (NUP35), Vacuolar protein sorting-associated protein 18 homolog (VPS 18), Dedicator of cytokinesis protein 7 (DOCK7), Nucleoporin p54 (NUP54), Ras-related GTP-binding protein C (RRAGC), Arf-GAP with Rho-GAP domain (ANK repeat and PH domain) (ARAPI), Exportin-5 (XPO5), Kinectin (KTN1), Chloride intracellular channel protein 6 (CLIC6), Voltage-gated potassium channel subunit beta-2 (KCNAB2), Exportin-5 (XPO5), Ras-related GTP-binding protein C (RRAGC), Ribosome-binding protein 1 (RRBP1), Acyl-CoA-binding domain-containing protein 6 (ACBD6), Chloride intracellular channel protein 5 (CLIC5), Pleckstrin homology domain-containing family A member (PLEKHA2), ADP-ribosylation factor-like protein 3 (ARL3), Protein transport protein Sec24C (SEC24C), Voltage-dependent anion-selective channel protein (VDAC3), Programmed cell death 6-interacting protein (PDCD6IP), Chloride intracellular channel protein 3 (CLIC3), Multivesicular body subunit 12A (FAM125A), Eukaryotic translation initiation factor 4E transporter (EIF4ENIF 1), NmrA-like family domain-containing protein 1 (NMRAL1), Nuclear pore complex protein Nup98-Nup96 (NUP98), Conserved oligomeric Golgi complex subunit 1 (COG1), Importin-4 (1P04), Pleckstrin homology domain-containing family A member (PLEKHA2), Cytoplasmic dynein 1 heavy chain 1 (DYNC1H1), DENN domain-containing protein 1C (DENND1C), Cytoplasmic dynein 1 heavy chain 1 (DYNC1H1), Protein ELYS (AHCTF), Trafficking protein particle complex subunit 1 (TRAPPC1), Guanine nucleotide-binding protein-like 3 (GNL3), or Importin-13 (IPO13). 
     In some embodiments, the cysteine containing protein is a chaperone. Exemplary cysteine containing proteins as chaperones include, but are not limited to, 60 kDa heat shock protein (mitochondrial) (HSPD1), T-complex protein 1 subunit eta (CCT7), T-complex protein 1 subunit epsilon (CCT5). Heat shock 70 kDa protein 4 (HSPA4), GrpE protein homolog 1 (mitochondrial) (GRPEL1), Tubulin-specific chaperone E (TBCE), Protein unc-45 homolog A (UNC45A), Serpin H1 (SERPINH1), Tubulin-specific chaperone D (TBCD). Peroxisomal biogenesis factor 19 (PEX19), BAG family molecular chaperone regulator 5 (BAG5), T-complex protein 1 subunit theta (CCT8), Protein canopy homolog 3 (CNPY3), DnaJ homolog subfamily C member 10 (DNAJC10), ATP-dependent Clp protease ATP-binding subunit clp (CLPX), or Midasin (MDN 1). 
     In some embodiments, the cysteine containing protein is an adapter, scaffolding or modulator protein. Exemplary cysteine containing proteins as adapter, scaffolding, or modulator proteins include, but are not limited to, Proteasome activator complex subunit 1 (PSME1), TIP41-like protein (TIPRL), Crk-like protein (CRKL), Cofilin-1 (CFL), Condensin complex subunit 1 (NCAPD2), Translational activator GCN1 (GCN1L1), Serine/threonine-protein phosphatase 2A 56 kDa regulatory (PPP2R5D), UPF0539 protein C7orf59 (C7orf59), Protein diaphanous homolog 1 (DIAPH1), Protein asunder homolog (Asun), Ras GTPase-activating-like protein IQGAP1 (IQGAP1), Sister chromatid cohesion protein PDS5 homolog A (PDS5A), Reticulon-4 (RTN4), Proteasome activator complex subunit 4 (PSME4), Condensin complex subunit 2 (NCAPH), Sister chromatid cohesion protein PDS5 homolog A (PDS5A), cAMP-dependent protein kinase type I-alpha regulatory (PRKARIA), Host cell factor 1 (HCFC1), Serine/threonine-protein phosphatase 4 regulatory (PPP4R2), Apoptotic chromatin condensation inducer in the nucleus (ACIN1), BRISC and BRCA1-A complex member 1 (BABAM1), Interferon-induced protein with tetratricopeptide (IFIT3), Ras association domain-containing protein 2 (RASSF2), Hsp70-binding protein 1 (HSPBP1). TBC1 domain family member 15 (TBC1D15), Dynamin-binding protein (DNMBP), Condensin complex subunit 1 (NCAPD2), Beta-2-syntrophin (SNTB2), Disks large homolog 1 (DLG1), TBC1 domain family member 13 (TBC ID13), Formin-binding protein 1-like (FNBPIL), Translational activator GCN1 (GCN1L1), GRB2-related adapter protein (GRAP), G2/mitotic-specific cyclin-B1 (CCNB1), Myotubularin-related protein 12 (MTMR12), Protein FADD (FADD), Translational activator GCN1 (GCNIL1), Wings apart-like protein homolog (WAPAL), cAMP-dependent protein kinase type II-beta regulatory (PRKAR2B), Malcavemin (CCM2), MPP1 55 kDa erythrocyte membrane protein, Actin filament-associated protein 1 (AFAP1), Tensin-3 (TNS3), tRNA methyltransferase 112 homolog (TRMT112). Symplekin (SYMPK), TBC1 domain family member 2A (TBC1D2), ATR-interacting protein (ATRIP), Ataxin-10 (ATXN10), Succinate dehydrogenase assembly factor 2 (mitochondrial) (SDHAF2), Formin-binding protein 1 (FNBPI), Myotubularin-related protein 12 (MTMR12), Interferon-induced protein with tetratricopeptide (IFIT3), Protein CBFA2T2 (CBFA2T2), Neutrophil cytosol factor 1 (NCF1), or Protein syndesmos (NUDT16L1). 
     In some embodiments, a cysteine containing protein comprises a protein illustrated in Tables 1-5 or Tables 7-9. In some instances, a cysteine containing protein comprises a protein illustrated in Table 1. In some embodiments, the cysteine containing protein comprises a cysteine residue denoted in Table 1. In some instances, a cysteine containing protein comprises a protein illustrated in Table 2. In some embodiments, the cysteine containing protein comprises a cysteine residue denoted in Table 2. In some instances, a cysteine containing protein comprises a protein illustrated in Table 3. In some embodiments, the cysteine containing protein comprises a cysteine residue denoted in Table 3. In some instances, a cysteine containing protein comprises a protein illustrated in Table 4. In some embodiments, the cysteine containing protein comprises a cysteine residue denoted in Table 4. In some instances, a cysteine containing protein comprises a protein illustrated in Table 5. In some embodiments, the cysteine containing protein comprises a cysteine residue denoted in Table 5. In some instances, a cysteine containing protein comprises a protein illustrated in Table 7. In some embodiments, the cysteine containing protein comprises a cysteine residue denoted in Table 7. In some instances, a cysteine containing protein comprises a protein illustrated in Table 8. In some embodiments, the cysteine containing protein comprises a cysteine residue denoted in Table 8. In some instances, a cysteine containing protein comprises a protein illustrated in Table 9. In some embodiments, the cysteine containing protein comprises a cysteine residue denoted in Table 9. In some instances, the cysteine containing protein is a modified protein, in which the protein is modified at a cysteine residue site by a small molecule fragment described herein, such as for example, by a small molecule fragment of Formula (I) described herein, a cysteine-reactive probe of Formula (II) described herein, or by a small molecule fragment illustrated in  FIG. 3 . 
     In some embodiments, described herein is a modified cysteine containing protein comprising a small molecule fragment having a covalent bond to a cysteine residue of a cysteine containing protein. In some instances, the cysteine containing protein is selected from Table 3. In some cases, one or more cysteine residues of each respective cysteine containing protein are denoted in Table 3. In some cases, a cysteine containing protein selected from Table 3 is modified by a small molecule fragment at at least one cysteine site denoted in Table 3 to generate a modified cysteine containing protein. In some cases, the cysteine containing protein is selected from AIP, PES1, IKBKB, XPO1, KDM4B, NR3C1, GSTP1, TNFAIP3, ACAT1, IRAK1, GNB2L1, IRF4, USP34. ZC3HAV1, USP7, PELI1, DCUN1D1, USP28, UBE2O, RRAGC, MLTK, USP22, KDM3A, or USP16. In some cases, the cysteine containing protein is selected from AIP, PES1, IKBKB, XPO1, GSTP1, ACAT1, IRAK1, IRF4, ZC3HAV1, USP7, PELI1, USP28, UBE2O, RRAGC, MLTK, USP22, KDM3A, or USP16. In some cases, the cysteine containing protein is selected from KDM4B, NR3C, TNFAIP3, USP7 or USP22. In some cases, the cysteine containing protein is selected from GNB2L1 or USP34. In some cases, the cysteine containing protein is DCUN1D1. In some cases, the cysteine containing protein is selected from PES1, IKBKB, GSTP1, ACAT1, IRAK1, ZC3HAV1 or RRAGC. In some cases, the cysteine containing protein is selected from XPO1, GNB2L1, USP34, UBE2O, MLTK or USP22. In some cases, the cysteine containing protein is selected from KDM4B or NR3C1. In some cases, the cysteine containing protein is selected from TNFAIP3, USP7, USP28, KDM3A or USP16. In some cases, the cysteine containing protein is selected from IRF4, PELI1, DCUNID1 or USP22. In some cases, the cysteine containing protein is AIP. In some cases, the cysteine containing protein is an enzyme and the enzyme is selected from IKBKB, KDM4B, GSTP1, TNFAIP3, ACAT1, IRAK1, USP34, USP7, PELI1, USP28, UBE2O, MLTK, USP22, KDM3A. or USP16. In some cases, the cysteine containing protein is a transcription factor or regulator and the transcription factor or regulator is selected from NR3C1, IRF4 or ZC3HAV1. In some cases, the cysteine containing protein is a channel, a transporter, or a receptor and the channel, transporter, or receptor is selected from GNB2L1 or RRAGC. In some cases, the cysteine containing protein is selected from AIP. PES1, XPO1 or DCUN1D1. In some cases, the cysteine containing protein is selected from PES1, CYR61, UBE2L6, XPO1, ADA, NR3C1, POU2F2, UCHL3, MGMT, ERCC3, ACAT1, STAT3, UBA7, CASP2, IDH2, LRBA, UBE2L3, RELB, IRF8, CASP8, PDIA6, PCK2, PFKFB4, PDE12, USP34, USP48, SMARCC2 or SAMHD1. In some cases, the cysteine containing protein is selected from PES1, CYR61, NR3C1, UCHL3, ERCC3, ACAT1, STAT3, CASP2, LRBA, UBE2L3. RELB, PDIA6, PCK2, PFKFB4, USP48 or SMARCC2. In some cases, the cysteine containing protein is selected from UBE2L6, POU2F2, MGMT, ACAT1, UBA7, CASP8, PDE12 or USP34. In some cases, the cysteine containing protein is selected from CYR61 or XPO1. In some cases, the cysteine containing protein is selected from ADA, MGMT, IDH2, IRF8 or SAMHD1. In some cases, the cysteine containing protein is selected from PES1, CYR61, XPO1, NR3C1 or SMARCC2. In some cases, the cysteine containing protein is selected from CYR61, UBE2L6, MGMT, ERCC3, ACAT1 or USP48. In some cases, the cysteine containing protein is selected from ADA, RELB or USP34. In some cases, the cysteine containing protein is selected from UCHL3. CASP2, IDH2. LRBA, CASP8, PCK2 or PDE12. In some cases, the cysteine containing protein is selected from MGMT. ACAT1, UBA7, UBE2L3 or IRF8. In some cases, the cysteine containing protein is selected from PFKFB4, ACAT1 or STAT3. In some cases, the cysteine containing protein is selected from POU2F2, PDIA6 or SAMHD1. In some cases, the cysteine containing protein is an enzyme and the enzyme is selected from UBE2L6, ADA, UCHL3. MGMT, ERCC3, ACAT1, UBA7, CASP2, IDH2, UBE2L3, CASP8, PDIA6, PCK2, PFKFB4, PDE12, USP34. USP48 or SAMHD1. In some cases, the cysteine containing protein is a transcription factor or a regulator and the transcription factor or regulator is selected from NR3C1, POU2F2, STAT3, RELB, IRF8 or SMARCC2. In some cases, the cysteine containing protein is selected from ZAP70, PRKCQ or PRMT1. In some cases, the cysteine containing protein is selected from ZAP70 or PRKCQ. In some cases, the cysteine containing protein is selected from CYR61, ZNF217, NCF1, IREB2, LRBA, CDK5, EP300, EZH2, UBE2S, VCPIP1, RRAGC or IRAK4. In some cases, the cysteine containing protein is selected from CYR61, ZNF217, IREB2, EP300, UBE2S, VCPIP1, RRAGC or IRAK4. In some cases, the cysteine containing protein is selected from NCF1, LRBA or CDK5. In some cases, the cysteine containing protein is EZH2. In some cases, the cysteine containing protein is selected from ZNF217, NCF1, CDK5, EP300 or IRAK4. In some cases, the cysteine containing protein is selected from CYR61, IREB2, LRBA or UBE2S. In some cases, the cysteine containing protein is selected from EZH2, VCPIP1 or RRAGC. In some cases, the cysteine containing protein is an enzyme and the enzyme is selected from CDK5, EP300, EZH2, UBE2S, VCPIP1 or IRAK4. In some cases, the cysteine containing protein is a transcription factor or a regulator and the transcription factor or regulator is selected from ZNF217 or IREB2. In some cases, the cysteine containing protein is an adapter, a scaffolding protein or a modulator protein and the adapter, scaffolding protein or the modulator protein is selected from NCF1. In some cases, the cysteine containing protein is a channel, a transporter or a receptor and the channel, transporter, or receptor is selected from RRAGC. In some cases, the cysteine containing protein is selected from CYR61 or LRBA. In some cases, the cysteine containing protein is about 20, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 150, 200, 250, 300, 350, 400, 450, 500, 600, 700, 800, 900, 1000 amino acid residues in length or more. In some cases, the cysteine residue of the modified cysteine containing protein has the structure SR, wherein R is selected from: 
     
       
         
         
             
             
         
       
     
     wherein R 1  is H, C1-C3 alkyl, or aryl; and F′ is the small molecule fragment moiety. In some cases, the small molecule fragment has a molecular weight of about 175, 200, 225, 250, 275, 300, 350, 400, 450, 500, 550, 600, 650, 700, 750, 800, 850, 900, 950, 1000 Dalton. or higher. In some cases, the molecular weight of the small molecule fragment is prior to enrichment with a halogen, a nonmetal, or a transition metal. In some embodiments, the molecular weight of the small molecule fragment is calculated based on carbon and hydrogen atoms and optionally further based on nitrogen, oxygen and/or sulfur atoms. In some embodiments, the molecular weight of the small molecule fragment does not include the molecular weight of a halogen, a transition metal or a combination thereof. In some cases, the small molecule fragment is a small molecule fragment of Formula (I): 
     
       
         
         
             
             
         
       
     
     wherein RM is a reactive moiety selected from a Michael acceptor moiety, a leaving group moiety, or a moiety capable of forming a covalent bond with the thiol group of a cysteine residue, and F is a small molecule fragment moiety. In some cases, the Michael acceptor moiety comprises an alkene or an alkyne moiety. In some cases, F is obtained from a compound library. In some cases, F is a small molecule fragment moiety illustrated in  FIG. 3 . In some cases, F further comprises a linker moiety that connects F to the carbonyl moiety. In some cases, the small molecule fragment binds irreversibly to the cysteine containing protein. In some cases, the small molecule fragment binds reversibly to the cysteine containing protein. 
     In some embodiments, described herein is a modified cysteine containing protein comprising a small molecule fragment having a covalent bond to a cysteine residue of a cysteine containing protein, in which the cysteine containing protein is selected from Table 10A, enzymes. In some cases, one or more cysteine residues of each respective cysteine containing protein are denoted in Table 10A. In some cases, a cysteine containing protein selected from Table 10 A is modified by a small molecule fragment at at least one cysteine site denoted in Table 10A to generate a modified cysteine containing protein. In some cases, the cysteine containing protein is about 20, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 150, 200, 250, 300, 350, 400, 450, 500, 600, 700, 800, 900, 1000 amino acid residues in length or more. In some cases, the cysteine residue of the modified cysteine containing protein has the structure SR, wherein R is selected from: 
     
       
         
         
             
             
         
       
     
     wherein R 1  is H, C1-C3 alkyl, or aryl; and F′ is the small molecule fragment moiety. In some cases, the small molecule fragment has a molecular weight of about 175, 200, 225, 250, 275, 300, 350, 400, 450, 500, 550, 600, 650, 700, 750, 800, 850, 900, 950, 1000 Dalton, or higher. In some cases, the molecular weight of the small molecule fragment is prior to enrichment with a halogen, a nonmetal, or a transition metal. In some embodiments, the molecular weight of the small molecule fragment is calculated based on carbon and hydrogen atoms and optionally further based on nitrogen, oxygen and/or sulfur atoms. In some embodiments, the molecular weight of the small molecule fragment does not include the molecular weight of a halogen, a transition metal or a combination thereof. In some cases, the small molecule fragment is a small molecule fragment of Formula (I): 
     
       
         
         
             
             
         
       
     
     wherein RM is a reactive moiety selected from a Michael acceptor moiety, a leaving group moiety, or a moiety capable of forming a covalent bond with the thiol group of a cysteine residue, and F is a small molecule fragment moiety. In some cases, the Michael acceptor moiety comprises an alkene or an alkyne moiety. In some cases, F is obtained from a compound library. In some cases. F is a small molecule fragment moiety illustrated in  FIG. 3 . In some cases, F further comprises a linker moiety that connects F to the carbonyl moiety. In some cases, the small molecule fragment binds irreversibly to the cysteine containing protein. In some cases, the small molecule fragment binds reversibly to the cysteine containing protein. 
     In some embodiments, described herein is a modified cysteine containing protein comprising a small molecule fragment having a covalent bond to a cysteine residue of a cysteine containing protein, in which the cysteine containing protein is selected from Table 10B, transcription factors and regulators. In some cases, one or more cysteine residues of each respective cysteine containing protein are denoted in Table 10B. In some cases, a cysteine containing protein selected from Table 10B is modified by a small molecule fragment at at least one cysteine site denoted in Table 10B to generate a modified cysteine containing protein. In some cases, the cysteine containing protein is about 20, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 150, 200, 250, 300, 350, 400, 450, 500, 600, 700, 800, 900, 1000 amino acid residues in length or more. In some cases, the cysteine residue of the modified cysteine containing protein has the structure SRI wherein R is selected from: 
     
       
         
         
             
             
         
       
     
     wherein R 1  is H, C1-C3 alkyl, or aryl; and F′ is the small molecule fragment moiety. In some cases, the small molecule fragment has a molecular weight of about 175, 200, 225, 250, 275, 300, 350, 400, 450, 500, 550, 600, 650, 700, 750, 800, 850, 900, 950, 1000 Dalton, or higher. In some cases, the molecular weight of the small molecule fragment is prior to enrichment with a halogen, a nonmetal, or a transition metal. In some embodiments, the molecular weight of the small molecule fragment is calculated based on carbon and hydrogen atoms and optionally further based on nitrogen, oxygen and/or sulfur atoms. In some embodiments, the molecular weight of the small molecule fragment does not include the molecular weight of a halogen, a transition metal or a combination thereof. In some cases, the small molecule fragment is a small molecule fragment of Formula (I): 
     
       
         
         
             
             
         
       
     
     wherein RM is a reactive moiety selected from a Michael acceptor moiety, a leaving group moiety, or a moiety capable of forming a covalent bond with the thiol group of a cysteine residue; and F is a small molecule fragment moiety. In some cases, the Michael acceptor moiety comprises an alkene or an alkyne moiety. In some cases, F is obtained from a compound library. In some cases, F is a small molecule fragment moiety illustrated in  FIG. 3 . In some cases, F further comprises a linker moiety that connects F to the carbonyl moiety. In some cases, the small molecule fragment binds irreversibly to the cysteine containing protein. In some cases, the small molecule fragment binds reversibly to the cysteine containing protein. 
     In some embodiments, described herein is a modified cysteine containing protein comprising a small molecule fragment having a covalent bond to a cysteine residue of a cysteine containing protein, in which the cysteine containing protein is selected from Table 10C, channels, transporters or receptors. In some cases, one or more cysteine residues of each respective cysteine containing protein are denoted in Table 10C. In some cases, a cysteine containing protein selected from Table 10C is modified by a small molecule fragment at at least one cysteine site denoted in Table 10C to generate a modified cysteine containing protein. In some cases, the cysteine containing protein is about 20, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 150, 200, 250, 300, 350, 400, 450, 500, 600, 700, 800, 900, 1000 amino acid residues in length or more. In some cases, the cysteine residue of the modified cysteine containing protein has the structure SRI wherein R is selected from: 
     
       
         
         
             
             
         
       
     
     wherein R 1  is H, C1-C3 alkyl, or aryl; and F′ is the small molecule fragment moiety. In some cases, the small molecule fragment has a molecular weight of about 175, 200, 225, 250, 275, 300, 350, 400, 450, 500, 550, 600, 650, 700, 750, 800, 850, 900, 950, 1000 Dalton, or higher. In some cases, the molecular weight of the small molecule fragment is prior to enrichment with a halogen, a nonmetal, or a transition metal. In some embodiments, the molecular weight of the small molecule fragment is calculated based on carbon and hydrogen atoms and optionally further based on nitrogen, oxygen and/or sulfur atoms. In some embodiments, the molecular weight of the small molecule fragment does not include the molecular weight of a halogen, a transition metal or a combination thereof. In some cases, the small molecule fragment is a small molecule fragment of Formula (I): 
     
       
         
         
             
             
         
       
     
     wherein RM is a reactive moiety selected from a Michael acceptor moiety, a leaving group moiety, or a moiety capable of forming a covalent bond with the thiol group of a cysteine residue; and F is a small molecule fragment moiety. In some cases, the Michael acceptor moiety comprises an alkene or an alkyne moiety. In some cases, F is obtained from a compound library. In some cases, F is a small molecule fragment moiety illustrated in  FIG. 3 . In some cases, F further comprises a linker moiety that connects F to the carbonyl moiety. In some cases, the small molecule fragment binds irreversibly to the cysteine containing protein. In some cases, the small molecule fragment binds reversibly to the cysteine containing protein. 
     In some embodiments, described herein is a modified cysteine containing protein comprising a small molecule fragment having a covalent bond to a cysteine residue of a cysteine containing protein, in which the cysteine containing protein is selected from Table 10D, adapter, scaffolding, or modulator proteins. In some cases, one or more cysteine residues of each respective cysteine containing protein are denoted in Table 10D. In some cases, a cysteine containing protein selected from Table 10D is modified by a small molecule fragment at at least one cysteine site denoted in Table 10D to generate a modified cysteine containing protein. In some cases, the cysteine containing protein is about 20, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 150, 200, 250, 300, 350, 400, 450, 500, 600, 700, 800, 900, 1000 amino acid residues in length or more. In some cases, the cysteine residue of the modified cysteine containing protein has the structure SR, wherein R is selected from: 
     
       
         
         
             
             
         
       
     
     wherein R 1  is H. C1-C3 alkyl, or aryl; and F′ is the small molecule fragment moiety. In some cases, the small molecule fragment has a molecular weight of about 175, 200, 225, 250, 275, 300, 350, 400, 450, 500, 550, 600, 650, 700, 750, 800, 850, 900, 950, 1000 Dalton, or higher. In some cases, the molecular weight of the small molecule fragment is prior to enrichment with a halogen, a nonmetal, or a transition metal. In some embodiments, the molecular weight of the small molecule fragment is calculated based on carbon and hydrogen atoms and optionally further based on nitrogen, oxygen and/or sulfur atoms. In some embodiments, the molecular weight of the small molecule fragment does not include the molecular weight of a halogen, a transition metal or a combination thereof. In some cases, the small molecule fragment is a small molecule fragment of Formula (I): 
     
       
         
         
             
             
         
       
     
     wherein RM is a reactive moiety selected from a Michael acceptor moiety, a leaving group moiety, or a moiety capable of forming a covalent bond with the thiol group of a cysteine residue; and F is a small molecule fragment moiety. In some cases, the Michael acceptor moiety comprises an alkene or an alkyne moiety. In some cases, F is obtained from a compound library. In some cases, F is a small molecule fragment moiety illustrated in  FIG. 3 . In some cases, F further comprises a linker moiety that connects F to the carbonyl moiety. In some cases, the small molecule fragment binds irreversibly to the cysteine containing protein. In some cases, the small molecule fragment binds reversibly to the cysteine containing protein. 
     In some embodiments, described herein is a modified cysteine containing protein comprising a small molecule fragment having a covalent bond to a cysteine residue of a cysteine containing protein, in which the cysteine containing protein is selected from Table 10E. In some cases, one or more cysteine residues of each respective cysteine containing protein are denoted in Table 10E. In some cases, a cysteine containing protein selected from Table 10E is modified by a small molecule fragment at at least one cysteine site denoted in Table 10E to generate a modified cysteine containing protein. In some cases, the cysteine containing protein is about 20, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 150, 200, 250, 300, 350, 400, 450, 500, 600, 700, 800, 900, 1000 amino acid residues in length or more. In some cases, the cysteine residue of the modified cysteine containing protein has the structure SR, wherein R is selected from 
     
       
         
         
             
             
         
       
     
     wherein R 1  is H, C1-C3 alkyl, or aryl; and F′ is the small molecule fragment moiety. In some cases, the small molecule fragment has a molecular weight of about 175, 200, 225, 250, 275, 300, 350, 400, 450, 500, 550, 600, 650, 700, 750, 800, 850, 900, 950, 1000 Dalton, or higher. In some cases, the molecular weight of the small molecule fragment is prior to enrichment with a halogen, a nonmetal, or a transition metal. In some embodiments, the molecular weight of the small molecule fragment is calculated based on carbon and hydrogen atoms and optionally further based on nitrogen, oxygen and/or sulfur atoms. In some embodiments, the molecular weight of the small molecule fragment does not include the molecular weight of a halogen, a transition metal or a combination thereof. In some cases, the small molecule fragment is a small molecule fragment of Formula (I): 
     
       
         
         
             
             
         
       
     
     wherein RM is a reactive moiety selected from a Michael acceptor moiety, a leaving group moiety, or a moiety capable of forming a covalent bond with the thiol group of a cysteine residue, and F is a small molecule fragment moiety. In some cases, the Michael acceptor moiety comprises an alkene or an alkyne moiety. In some cases, F is obtained from a compound library. In some cases, F is a small molecule fragment moiety illustrated in  FIG. 3 . In some cases, F further comprises a linker moiety that connects F to the carbonyl moiety. In some cases, the small molecule fragment binds irreversibly to the cysteine containing protein. In some cases, the small molecule fragment binds reversibly to the cysteine containing protein. 
     In some embodiments, described herein is a modified cysteine containing protein comprising a small molecule fragment having a covalent bond to a cysteine residue of a cysteine containing protein, in which the cysteine containing protein comprises the motif X p C*Z, wherein X, is a polar residue, C* denotes the site of modification, and Z is any amino acid. In some cases, the cysteine containing protein is selected from Table 3. In some cases, the cysteine containing protein is selected from AIP, PES1, IKBKB, XPO1. KDM4B, NR3C1, GSTP1. TNFAIP3, ACAT1, IRAK1, GNB2L1, IRF4, USP34, ZC3HAV1, USP7, PELI1, DCUN1D1, USP28, UBE2O, RRAGC, MLTK, USP22, KDM3A, or USP16. 
     In some instances, described herein is a modified cysteine containing protein comprising a small molecule fragment having a covalent bond to a cysteine residue of a cysteine containing protein, in which the cysteine containing protein comprises the motif X p C*X n , wherein X p  is a polar residue. C* denotes the site of modification, and X n  is a nonpolar residue. In some cases, the cysteine containing protein is selected from Table 3. In some cases, the cysteine containing protein is selected from AIP, PES1, IKBKB, XPO1, GSTP1, ACAT1, IRAK1, IRF4, ZC3HAV1, USP7, PELI1, USP28, UBE2O, RRAGC, MLTK, USP22, KDM3A, or USP16. 
     In some instances, described herein is a modified cysteine containing protein comprising a small molecule fragment having a covalent bond to a cysteine residue of a cysteine containing protein, in which the cysteine containing protein comprises the motif X p C*X p , wherein X p  is a polar residue and C* denotes the site of modification. In some cases, the cysteine containing protein is selected from Table 3. In some cases, the cysteine containing protein is selected from KDM4B, NR3C1, TNFAIP3, USP7 or USP22. 
     In some instances, described herein is a modified cysteine containing protein comprising a small molecule fragment having a covalent bond to a cysteine residue of a cysteine containing protein, in which the cysteine containing protein comprises the motif X p C*X b , wherein X p  is a polar residue, C* denotes the site of modification, and X b  is a basic residue. In some cases, the cysteine containing protein is selected from Table 3. In some cases, the cysteine containing protein is selected from GNB2L1 or USP34. 
     In some instances, described herein is a modified cysteine containing protein comprising a small molecule fragment having a covalent bond to a cysteine residue of a cysteine containing protein, in which the cysteine containing protein comprises the motif X p C*X a , wherein X p  is a polar residue, C* denotes the site of modification, and X a  is an acidic residue. In some cases, the cysteine containing protein is selected from Table 3. In some cases, the cysteine containing protein is DCUN1D1. 
     In some instances, described herein is a modified cysteine containing protein comprising a small molecule fragment having a covalent bond to a cysteine residue of a cysteine containing protein, in which the cysteine containing protein comprises the motif SC*Z, wherein C* denotes the site of modification, and Z is any amino acid. In some cases, the cysteine containing protein is selected from Table 3. In some cases, the cysteine containing protein is selected from PES1, IKBKB, GSTP1, ACAT1, IRAK1, ZC3HAV1 or RRAGC. 
     In some instances, described herein is a modified cysteine containing protein comprising a small molecule fragment having a covalent bond to a cysteine residue of a cysteine containing protein, in which the cysteine containing protein comprises the motif NC*Z, wherein C* denotes the site of modification, and Z is any amino acid. In some cases, the cysteine containing protein is selected from Table 3. In some cases, the cysteine containing protein is selected from XPO1, GNB2L1, USP34, UBE2O, MLTK or USP22. 
     In some instances, described herein is a modified cysteine containing protein comprising a small molecule fragment having a covalent bond to a cysteine residue of a cysteine containing protein, in which the cysteine containing protein comprises the motif YC*Z, wherein C* denotes the site of modification, and Z is any amino acid. In some cases, the cysteine containing protein is selected from Table 3. In some cases, the cysteine containing protein is selected from KDM4B or NR3C1. 
     In some instances, described herein is a modified cysteine containing protein comprising a small molecule fragment having a covalent bond to a cysteine residue of a cysteine containing protein, in which the cysteine containing protein comprises the motif TC*Z, wherein C* denotes the site of modification, and Z is any amino acid. In some cases, the cysteine containing protein is selected from Table 3. In some cases, the cysteine containing protein is selected from TNFAIP3, USP7, USP28, KDM3A or USP16. 
     In some instances, described herein is a modified cysteine containing protein comprising a small molecule fragment having a covalent bond to a cysteine residue of a cysteine containing protein, in which the cysteine containing protein comprises the motif QC*Z, wherein C* denotes the site of modification, and Z is any amino acid. In some cases, the cysteine containing protein is selected from Table 3. In some cases, the cysteine containing protein is selected from IRF4, PELI1, DCUN1D1 or USP22. 
     In some instances, described herein is a modified cysteine containing protein comprising a small molecule fragment having a covalent bond to a cysteine residue of a cysteine containing protein, in which the cysteine containing protein comprises the motif CC*Z, wherein C* denotes the site of modification, and Z is any amino acid. In some cases, the cysteine containing protein is selected from Table 3. In some cases, the cysteine containing protein is AIP. 
     In some instances, described herein is a modified cysteine containing protein comprising a small molecule fragment having a covalent bond to a cysteine residue of a cysteine containing protein, in which the cysteine containing protein is an enzyme and the enzyme comprises the motif X p C*Z, wherein X p  is a polar residue, C* denotes the site of modification, and Z is any amino acid. In some cases, the cysteine containing protein is selected from Table 3. In some cases, the enzyme is selected from IKBKB, KDM4B, GSTP1, TNFAIP3, ACAT1, IRAK1, USP34, USP7, PELI1, USP28, UBE20O, MLTK, USP22, KDM3A, or USP16. 
     In some instances, described herein is a modified cysteine containing protein comprising a small molecule fragment having a covalent bond to a cysteine residue of a cysteine containing protein, in which the cysteine containing protein is a transcription factor or a regulator and the transcription factor or regulator comprises the motif X p C*Z, wherein X p  is a polar residue, C* denotes the site of modification, and Z is any amino acid. In some cases, the cysteine containing protein is selected from Table 3. In some cases, the transcription factor or regulator is selected from NR3C1, IRF4 or ZC3HAV1. 
     In some instances, described herein is a modified cysteine containing protein comprising a small molecule fragment having a covalent bond to a cysteine residue of a cysteine containing protein, in which the cysteine containing protein is a channel, transporter or a receptor and the channel, transporter or receptor comprises the motif X p C*Z, wherein X p  is a polar residue, C* denotes the site of modification, and Z is any amino acid. In some cases, the cysteine containing protein is selected from Table 3. In some cases, the channel, transporter, or receptor is selected from GNB2L1 or RRAGC. 
     In some instances, described herein is a modified cysteine containing protein comprising a small molecule fragment having a covalent bond to a cysteine residue of a cysteine containing protein, in which the cysteine containing protein comprises the motif X p C*Z, wherein X p  is a polar residue. C* denotes the site of modification, and Z is any amino acid. In some cases, the cysteine containing protein is selected from Table 3. In some cases, the cysteine containing protein is selected from AIP, PES1, XPO1 or DCUN1D1. 
     In some instances, described herein is a modified cysteine containing protein comprising a small molecule fragment having a covalent bond to a cysteine residue of a cysteine containing protein, in which the cysteine containing protein comprises the motif X n C*Z, wherein X n  is a nonpolar residue, C* denotes the site of modification, and Z is any amino acid. In some cases, the cysteine containing protein is selected from Table 3. In some cases, the cysteine containing protein is selected from PES1, CYR61, UBE2L6, XPO1, ADA, NR3C1, POU2F2, UCHL3, MGMT, ERCC3, ACAT1, STAT3, UBA7, CASP2, IDH2, LRBA, UBE2L3, RELB, IRF8, CASP8, PDIA6, PCK2, PFKFB4, PDE12, USP34, USP48, SMARCC2 or SAMHD1. 
     In some instances, described herein is a modified cysteine containing protein comprising a small molecule fragment having a covalent bond to a cysteine residue of a cysteine containing protein, in which the cysteine containing protein comprises the motif X n C*X n , wherein X n  is a nonpolar residue and C* denotes the site of modification. In some cases, the cysteine containing protein is selected from Table 3. In some cases, the cysteine containing protein is selected from PES1, CYR61, NR3C1, UCHL3, ERCC3, ACAT1, STAT3, CASP2, LRBA, UBE2L3, RELB, PDIA6, PCK2, PFKFB4, USP48 or SMARCC2. 
     In some instances, described herein is a modified cysteine containing protein comprising a small molecule fragment having a covalent bond to a cysteine residue of a cysteine containing protein, in which the cysteine containing protein comprises the motif X n C*X p , wherein X n  is a nonpolar residue, C* denotes the site of modification, and X p  is a polar residue. In some cases, the cysteine containing protein is selected from Table 3. In some cases, the cysteine containing protein is selected from UBE2L6, POU2F2, MGMT, ACAT1, UBA7, CASP8, PDE12 or USP34. 
     In some instances, described herein is a modified cysteine containing protein comprising a small molecule fragment having a covalent bond to a cysteine residue of a cysteine containing protein, in which the cysteine containing protein comprises the motif X n C*X a , wherein X n  is a nonpolar residue, C* denotes the site of modification, and X a  is an acidic residue. In some cases, the cysteine containing protein is selected from Table 3. In some cases, the cysteine containing protein is selected from CYR61 or XPO1. 
     In some instances, described herein is a modified cysteine containing protein comprising a small molecule fragment having a covalent bond to a cysteine residue of a cysteine containing protein, in which the cysteine containing protein comprises the motif X a C*X b , wherein X n  is a nonpolar residue, C* denotes the site of modification, and X b  is a basic residue. In some cases, the cysteine containing protein is selected from Table 3. In some cases, the cysteine containing protein is selected from ADA, MGMT, IDH2, IRF8 or SAMHD1. 
     In some instances, described herein is a modified cysteine containing protein comprising a small molecule fragment having a covalent bond to a cysteine residue of a cysteine containing protein, in which the cysteine containing protein comprises the motif LC*Z, wherein C* denotes the site of modification, and Z is any amino acid. In some cases, the cysteine containing protein is selected from Table 3. In some cases, the cysteine containing protein is selected from PES1, CYR61, XPO1, NR3C1 or SMARCC2. 
     In some instances, described herein is a modified cysteine containing protein comprising a small molecule fragment having a covalent bond to a cysteine residue of a cysteine containing protein, in which the cysteine containing protein comprises the motif PC*Z, wherein C* denotes the site of modification, and Z is any amino acid. In some cases, the cysteine containing protein is selected from Table 3. In some cases, the cysteine containing protein is selected from CYR61, UBE2L6, MGMT, ERCC3, ACAT1 or USP48. 
     In some instances, described herein is a modified cysteine containing protein comprising a small molecule fragment having a covalent bond to a cysteine residue of a cysteine containing protein, in which the cysteine containing protein comprises the motif GC*Z, wherein C* denotes the site of modification, and Z is any amino acid. In some cases, the cysteine containing protein is selected from Table 3. In some cases, the cysteine containing protein is selected from ADA, RELB or USP34. 
     In some instances, described herein is a modified cysteine containing protein comprising a small molecule fragment having a covalent bond to a cysteine residue of a cysteine containing protein, in which the cysteine containing protein comprises the motif AC*Z, wherein C* denotes the site of modification, and Z is any amino acid. In some cases, the cysteine containing protein is selected from Table 3. In some cases, the cysteine containing protein is selected from UCHL3, CASP2. IDH2, LRBA. CASP8, PCK2 or PDE12. 
     In some instances, described herein is a modified cysteine containing protein comprising a small molecule fragment having a covalent bond to a cysteine residue of a cysteine containing protein, in which the cysteine containing protein comprises the motif VC*Z, wherein C* denotes the site of modification, and Z is any amino acid. In some cases, the cysteine containing protein is selected from Table 3. In some cases, the cysteine containing protein is selected from MGMT, ACAT1, UBA7, UBE2L3 or IRF8. 
     In some instances, described herein is a modified cysteine containing protein comprising a small molecule fragment having a covalent bond to a cysteine residue of a cysteine containing protein, in which the cysteine containing protein comprises the motif IC*Z, wherein C* denotes the site of modification, and Z is any amino acid. In some cases, the cysteine containing protein is selected from Table 3. In some cases, the cysteine containing protein is selected from PFKFB4, ACAT1 or STAT3. 
     In some instances, described herein is a modified cysteine containing protein comprising a small molecule fragment having a covalent bond to a cysteine residue of a cysteine containing protein, in which the cysteine containing protein comprises the motif X r C*Z, wherein X r  denotes an aromatic residue, C* denotes the site of modification, and Z is any amino acid. In some cases, the cysteine containing protein is selected from Table 3. In some cases, the cysteine containing protein is selected from POU2F2, PDIA6 or SAMHD1. 
     In some instances, described herein is a modified cysteine containing protein comprising a small molecule fragment having a covalent bond to a cysteine residue of a cysteine containing protein, in which the cysteine containing protein is an enzyme and the enzyme comprises the motif X n C*Z, wherein X n  is a nonpolar residue, C* denotes the site of modification, and Z is any amino acid. In some cases, the cysteine containing protein is selected from Table 3. In some cases, the enzyme is selected from UBE2L6, ADA, UCHL3, MGMT, ERCC3, ACAT1, UBA7, CASP2, IDH2, UBE2L3, CASP8, PDIA6, PCK2, PFKFB4, PDE12, USP34, USP48 or SAMHD1. 
     In some instances, described herein is a modified cysteine containing protein comprising a small molecule fragment having a covalent bond to a cysteine residue of a cysteine containing protein, in which the cysteine containing protein is a transcription factor or a regulator and the transcription factor or regulator comprises the motif X n C*Z, wherein X n  is a nonpolar residue, C* denotes the site of modification, and Z is any amino acid. In some cases, the cysteine containing protein is selected from Table 3. In some cases, the transcription factor or regulator is selected from NR3C1, POU2F2, STAT3, RELB, IRF8 or SMARCC2. 
     In some instances, described herein is a modified cysteine containing protein comprising a small molecule fragment having a covalent bond to a cysteine residue of a cysteine containing protein, in which the cysteine containing protein comprises the motif X n C*Z, wherein X n  is a nonpolar residue, C* denotes the site of modification, and Z is any amino acid. In some cases, the cysteine containing protein is selected from Table 3. In some cases, the cysteine containing protein is selected from PES1, CYR61, XPO1 or LRBA. 
     In some instances, described herein is a modified cysteine containing protein comprising a small molecule fragment having a covalent bond to a cysteine residue of a cysteine containing protein, in which the cysteine containing protein comprises the motif X a C*Z, wherein X a  is an acidic residue, C* denotes the site of modification, and Z is any amino acid. In some cases, the cysteine containing protein is selected from Table 3. In some cases, the cysteine containing protein is selected from ZAP70, PRKCQ or PRMT1. 
     In some instances, described herein is a modified cysteine containing protein comprising a small molecule fragment having a covalent bond to a cysteine residue of a cysteine containing protein, in which the cysteine containing protein comprises the motif EC*Z, wherein C* denotes the site of modification, and Z is any amino acid. In some cases, the cysteine containing protein is selected from Table 3. In some cases, the cysteine containing protein is selected from ZAP70 or PRKCQ. 
     In some instances, described herein is a modified cysteine containing protein comprising a small molecule fragment having a covalent bond to a cysteine residue of a cysteine containing protein, in which the cysteine containing protein comprises the motif X b C*Z, wherein X b  is a basic residue, C* denotes the site of modification, and Z is any amino acid. In some cases, the cysteine containing protein is selected from Table 3. In some cases, the cysteine containing protein is selected from CYR61, ZNF217, NCF1, IREB2, LRBA, CDK5, EP300, EZH2, UBE2S, VCPIP1, RRAGC or IRAK4. 
     In some instances, described herein is a modified cysteine containing protein comprising a small molecule fragment having a covalent bond to a cysteine residue of a cysteine containing protein, in which the cysteine containing protein comprises the motif X b C*X n , wherein X b  is a basic residue, C* denotes the site of modification, and X n  is a nonpolar residue. In some cases, the cysteine containing protein is selected from Table 3. In some cases, the cysteine containing protein is selected from CYR61, ZNF217, IREB2, EP300, UBE2S, VCPIP1, RRAGC or IRAK4. 
     In some instances, described herein is a modified cysteine containing protein comprising a small molecule fragment having a covalent bond to a cysteine residue of a cysteine containing protein, in which the cysteine containing protein comprises the motif X b C*X p , wherein X b  is a basic residue, C* denotes the site of modification, and X p  is a polar residue. In some cases, the cysteine containing protein is selected from Table 3. In some cases, the cysteine containing protein is selected from NCF1, LRBA or CDK5. 
     In some instances, described herein is a modified cysteine containing protein comprising a small molecule fragment having a covalent bond to a cysteine residue of a cysteine containing protein, in which the cysteine containing protein comprises the motif X b C*X b , wherein X b  is a basic residue and C* denotes the site of modification. In some cases, the cysteine containing protein is selected from Table 3. In some cases, the cysteine containing protein is EZH2. 
     In some instances, described herein is a modified cysteine containing protein comprising a small molecule fragment having a covalent bond to a cysteine residue of a cysteine containing protein, in which the cysteine containing protein comprises the motif RC*Z, wherein C* denotes the site of modification, and Z is any amino acid. In some cases, the cysteine containing protein is selected from Table 3. In some cases, the cysteine containing protein is selected from ZNF217, NCF1, CDK5, EP300 or IRAK4. 
     In some instances, described herein is a modified cysteine containing protein comprising a small molecule fragment having a covalent bond to a cysteine residue of a cysteine containing protein, in which the cysteine containing protein comprises the motif KC*Z, wherein C* denotes the site of modification, and Z is any amino acid. In some cases, the cysteine containing protein is selected from Table 3. In some cases, the cysteine containing protein is selected from CYR61, IREB2, LRBA or UBE2S. 
     In some instances, described herein is a modified cysteine containing protein comprising a small molecule fragment having a covalent bond to a cysteine residue of a cysteine containing protein, in which the cysteine containing protein comprises the motif HC*Z, wherein C* denotes the site of modification, and Z is any amino acid. In some cases, the cysteine containing protein is selected from Table 3. In some cases, the cysteine containing protein is selected from EZH2, VCPIP1 or RRAGC. 
     In some instances, described herein is a modified cysteine containing protein comprising a small molecule fragment having a covalent bond to a cysteine residue of a cysteine containing protein, in which the cysteine containing protein is an enzyme and the enzyme comprises the motif X b C*Z, wherein X b  is a basic residue, C* denotes the site of modification, and Z is any amino acid. In some cases, the cysteine containing protein is selected from Table 3. In some cases, the enzyme is selected from CDK5, EP300, EZH2, UBE2S, VCPIP1 or IRAK4. 
     In some instances, described herein is a modified cysteine containing protein comprising a small molecule fragment having a covalent bond to a cysteine residue of a cysteine containing protein, in which the cysteine containing protein is a transcription factor or a regulator and the transcription factor or regulator comprises the motif X b C*Z, wherein X b  is a basic residue, C* denotes the site of modification, and Z is any amino acid. In some cases, the cysteine containing protein is selected from Table 3. In some cases, the transcription factor or regulator is selected from ZNF217 or IREB2. 
     In some instances, described herein is a modified cysteine containing protein comprising a small molecule fragment having a covalent bond to a cysteine residue of a cysteine containing protein, in which the cysteine containing protein is an adapter, a scaffolding protein, or a modulator protein and the adapter, scaffolding protein or the modulator protein comprises the motif X b C*Z, wherein X b  is a basic residue. C* denotes the site of modification, and Z is any amino acid. In some cases, the cysteine containing protein is selected from Table 3. In some cases, the adapter, scaffolding protein or the modulator protein is selected from NCF1. 
     In some instances, described herein is a modified cysteine containing protein comprising a small molecule fragment having a covalent bond to a cysteine residue of a cysteine containing protein, in which the cysteine containing protein is a channel, a transporter, or a receptor and the channel, transporter, or receptor comprises the motif X b C*Z, wherein X b  is a basic residue, C* denotes the site of modification, and Z is any amino acid. In some cases, the cysteine containing protein is selected from Table 3. In some cases, the channel, transporter, or receptor is selected from RRAGC. 
     In some instances, described herein is a modified cysteine containing protein comprising a small molecule fragment having a covalent bond to a cysteine residue of a cysteine containing protein, in which the cysteine containing protein comprises the motif X b C*Z, wherein X b  is a basic residue, C* denotes the site of modification, and Z is any amino acid. In some cases, the cysteine containing protein is selected from Table 3. In some cases, the cysteine containing protein is selected from CYR61 or LRBA. 
     In some cases, a cysteine containing protein described above comprises about 20, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 150, 200, 250, 300, 350, 400, 450, 500, 600, 700, 800, 900, 1000 amino acid residues in length or more. 
     In some cases, the cysteine residue of a modified cysteine containing protein described above has the structure SR, wherein R is selected from: 
     
       
         
         
             
             
         
       
     
     wherein R 1  is H, C1-C3 alkyl, or aryl; and F′ is the small molecule fragment moiety. In some cases, the small molecule fragment has a molecular weight of about 175, 200, 225, 250, 275, 300, 350, 400, 450, 500, 550, 600, 650, 700, 750, 800, 850, 900, 950, 1000 Dalton, or higher. In some cases, the molecular weight of the small molecule fragment is prior to enrichment with a halogen, a nonmetal, or a transition metal. In some embodiments, the molecular weight of the small molecule fragment is calculated based on carbon and hydrogen atoms and optionally further based on nitrogen, oxygen and/or sulfur atoms. In some embodiments, the molecular weight of the small molecule fragment does not include the molecular weight of a halogen, a transition metal or a combination thereof. In some cases, the small molecule fragment is a small molecule fragment of Formula (I): 
     
       
         
         
             
             
         
       
     
     wherein RM is a reactive moiety selected from a Michael acceptor moiety, a leaving group moiety, or a moiety capable of forming a covalent bond with the thiol group of a cysteine residue; and F is a small molecule fragment moiety. In some cases, the Michael acceptor moiety comprises an alkene or an alkyne moiety. In some cases, F is obtained from a compound library. In some cases, F is a small molecule fragment moiety illustrated in  FIG. 3 . In some cases, F further comprises a linker moiety that connects F to the carbonyl moiety. In some cases, the small molecule fragment binds irreversibly to a cysteine containing protein described above. In some cases, the small molecule fragment binds reversibly to a cysteine containing protein described above. 
     Compositions, Cells, and Cell Populations 
     Disclosed herein also include compositions of a small molecule fragment conjugated to a cysteine containing protein, a cysteine-reactive probe conjugated to a cysteine containing protein, and treated sample compositions. In some embodiments, a composition described herein comprises a small molecule fragment of Formula (I): 
     
       
         
         
             
             
         
       
     
     wherein:
         RM is a reactive moiety selected from a Michael acceptor moiety, a leaving group moiety, or a moiety capable of forming a covalent bond with the thiol group of a cysteine residue; and   F is a small molecule fragment moiety; and   a cysteine containing protein wherein the cysteine containing protein is covalently bond to the small molecule fragment.       

     In some embodiments, also described herein is a composition that comprises a cysteine-reactive probe of Formula (II): 
     
       
         
         
             
             
         
       
     
     wherein:
         RM is a reactive moiety selected from a Michael acceptor moiety, a leaving group moiety, or a moiety capable of forming a covalent bond to the thiol group of a cysteine residue; and   AHM is an affinity handle moiety; and   a cysteine containing protein wherein the cysteine containing protein is covalently bond to the cysteine-reactive probe.       

     In some embodiments, also described herein is a composition that comprises an isolated sample wherein the isolated sample is an isolated cell or a tissue sample; and a cysteine-reactive probe to be assayed for its ability to interact with a cysteine containing protein expressed in the isolated sample. 
     Disclosed herein further include isolated treated cell and cell populations. In some embodiments, described herein is an isolated treated cell that comprises a cysteine-reactive probe covalently attached to a cysteine containing protein. In some instances, the isolated treated cell further comprises a set of cysteine-reactive probes wherein each of the cysteine-reactive probes is covalently attached to a cysteine containing protein. 
     In some embodiments, described herein is an isolated treated cell that comprises a small molecule fragment covalently attached to a cysteine containing protein. In some instances, the isolated treated cell further comprises a set of small molecule fragments wherein each of the small molecule fragment is covalently attached to a cysteine containing protein. In some instances, the isolated treated cell further comprises a cysteine-reactive probe. In some instances, the isolated treated cell further comprises a set of cysteine-reactive probes. 
     In some embodiments, also described herein is an isolated treated population of cells that comprises a set of cysteine-reactive probes covalently attached to cysteine containing proteins. 
     In some embodiments, further described herein is an isolated treated population of cells that comprises a set of small molecule fragments covalently attached to cysteine containing proteins. In some instances, the isolated treated population of cells further comprises a set of cysteine-reactive probes. 
     As disclosed elsewhere herein, the small molecule fragment is a small molecule fragment of Formula (I): 
     
       
         
         
             
             
         
       
     
     wherein:
         RM is a reactive moiety selected from a Michael acceptor moiety, a leaving group moiety, or a moiety capable of forming a covalent bond with the thiol group of a cysteine residue; and   F is a small molecule fragment moiety.       

     In some instances, the Michael acceptor moiety comprises an alkene or an alkyne moiety. In some cases, F is obtained from a compound library. In some embodiments, the compound library comprises ChemBridge fragment library, Pyramid Platform Fragment-Based Drug Discovery, Maybridge fragment library, FRGx from AnalytiCon, TCI-Frag from AnCoreX, Bio Building Blocks from ASINEX, BioFocus 3D from Charles River, Fragments of Life (FOL) from Emerald Bio. Enamine Fragment Library, IOTA Diverse 1500, BIONET fragments library, Life Chemicals Fragments Collection, OTAVA fragment library, Prestwick fragment library, Selcia fragment library, TimTec fragment-based library, Allium from Vitas-M Laboratory, or Zenobia fragment library. In some cases, F is a small molecule fragment moiety illustrated in  FIG. 3 . In some cases, F further comprises a linker moiety that connects F to the carbonyl moiety. In some embodiments, the small molecule fragment is a small molecule fragment illustrated in  FIG. 3 . 
     Also described elsewhere herein, the cysteine-reactive probe is a cysteine-reactive probe of Formula (II): 
     
       
         
         
             
             
         
       
     
     wherein:
         RM is a reactive moiety selected from a Michael acceptor moiety, a leaving group moiety, or a moiety capable of forming a covalent bond to the thiol group of a cysteine residue; and   AHM is an affinity handle moiety.       

     In some embodiments, the Michael acceptor moiety comprises an alkene or an alkyne moiety. In some instances, the affinity handle moiety comprises an affinity handle and a binding moiety that facilitates covalent interaction of the cysteine-reactive probe to a cysteine residue of a cysteine-containing protein. In some cases, the binding moiety is a small molecule fragment obtained from a compound library. In some cases, the compound library comprises ChemBridge fragment library, Pyramid Platform Fragment-Based Drug Discovery, Maybridge fragment library. FRGx from AnalytiCon, TCI-Frag from AnCoreX, Bio Building Blocks from ASINEX, BioFocus 3D from Charles River, Fragments of Life (FOL) from Emerald Bio, Enamine Fragment Library, IOTA Diverse 1500, BIONET fragments library, Life Chemicals Fragments Collection, OTAVA fragment library, Prestwick fragment library, Selcia fragment library, TimTec fragment-based library, Allium from Vitas-M Laboratory, or Zenobia fragment library. 
     In some instances, the affinity handle is a bioorthogonal affinity handle. In some cases, the affinity handle comprises a carbodiimide, N-hydroxysuccinimide (NHS) ester, imidoester, pentafluorophenyl ester, hydroxymethyl phosphine, maleimide, haloacetyl, pyridyl disulfide, thiosulfonate, vinylsulfone, hydrazide, alkoxyamine, alkyne, azide, or isocyanate group. In some cases, the affinity handle comprises an alkyne or an azide group. In some instances, the affinity handle is further conjugated to an affinity ligand. In some instances, the affinity ligand comprises a chromophore, a labeling group, or a combination thereof. In some cases, the chromophore comprises fluorochrome, non-fluorochrome chromophore, quencher, an absorption chromophore, fluorophore, organic dye, inorganic dye, metal chelate, or a fluorescent enzyme substrate. In some cases, the labeling group is biotin moiety, streptavidin moiety, bead, resin, a solid support, or a combination thereof. In some instances, the affinity handle moiety further comprises a chromophore. In some embodiments, the cysteine-reactive probe is a cysteine-reactive probe illustrated in  FIG. 3 . 
     Further described elsewhere herein, the cell or cell population is obtained from any mammal, such as human or non-human primates. In some embodiments, the cell or cell population is an epithelial cell, connective tissue cell, hormone secreting cell, a nerve cell, a skeletal muscle cell, a blood cell, or an immune system cell. In additional embodiments, the cell or cell population is cancerous or is obtained from a tumor site. 
     Polypeptides Comprising a Cysteine Interacting Site 
     Further disclosed herein are polypeptides that comprise one or more of the cysteine interacting sites identified by a method described herein. In some embodiments, described herein is an isolated and purified polypeptide that comprises at least 90% sequence identity to at least seven contiguous amino acids of an amino acid sequence selected from Tables 1-3 or 8-9. In some embodiments, the isolated and purified polypeptide comprises at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to at least seven contiguous amino acids of an amino acid sequence selected from Tables 1-3 or 8-9. In some embodiments, the isolated and purified polypeptide comprises 100% sequence identity to at least seven contiguous amino acids of an amino acid sequence selected from Tables 1-3 or 8-9. In some instances, the isolated and purified polypeptide consists 100% sequence identity to the full length of an amino acid sequence selected from Tables 1-3 or 8-9. In some instances, the isolated and purified polypeptide is at most 50 amino acids in length. 
     In some embodiments, additionally described herein include nucleic acid encoding a polypeptide that comprises at least 90% sequence identity at least seven contiguous amino acids of an amino acid sequence selected from Tables 1-3 or 8-9. In some embodiments, the nucleic acid encoding a polypeptide comprises at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity at least seven contiguous amino acids of an amino acid sequence selected from Tables 1-3 or 8-9. In some embodiments, the nucleic acid encoding a polypeptide comprises 100% sequence identity at least seven contiguous amino acids of an amino acid sequence selected from Tables 1-3 or 8-9. In some embodiments, the nucleic acid encoding a polypeptide consists 100% sequence identity to the full length of an amino acid sequence selected from Tables 1-3 or 8-9. 
     In some embodiments, further disclosed herein include a method of mapping a biologically active cysteine site on a protein, which comprises harvesting a set of cysteine-reactive probe-protein complexes from a sample wherein the cysteine-reactive probe comprises a reactive moiety capable of forming a covalent bond with a cysteine residue located on the cysteine containing protein; analyzing the set of cysteine-reactive probe-protein complexes by a proteomic analysis means; and based on the previous step, mapping the biologically active cysteine site on the protein. 
     In some embodiments, the analyzing further comprises treating the set of cysteine-reactive probe-protein complexes with a protease to generate a set of protein fragments. The protease is a serine protease, a threonine protease, a cysteine protease, an aspartate protease, a glutamic acid protease, or a metalloprotease. In some instances, the protease is a serine protease. In some instances, the protease is trypsin. In some instances, cysteine-reactive probe-protein complex is further attached to a labeling group such as a biotin moiety. In some instances, the labeling group such as a biotin moiety further comprises a linker. In some instances, the linker is a peptide. In some instances, the peptide linker is about 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20 or more amino acid residues in length. In some instances, the peptide linker contains a cleavage site. A non-limiting list of cleavage sites includes Tobacco Etch Virus (TEV), thrombin (Thr), enterokinase (EKT), activated Factor X (Xa), or human Rhinovirus 3C protease (3C/PreScission). In some instances, the peptide linker contains a TEV protease cleavage site. In some instances, the TEV protease cleavage site comprises the following sequence Gly-Gln-Phe-Tyr-Leu-Asn-Glu (SEQ ID NO: 860). In some instances, the biotin moiety is further coupled to a bead (e.g. a streptavidin-coupled bead). 
     In some instances, the protein from the cysteine-reactive probe-protein complex attached to the bead (via a biotin moiety comprising a linker and attached to a streptavidin-coupled bead) is digested with trypsin, and the immobilized peptide or protein fragment is further separated and collected. In some instances, the collected peptide or protein fragment is then digested by a protease (e.g. TEV protease), and the treated protein fragment is then separated, and collected for analysis. In some instances, the analysis is a proteomic analysis as described above and elsewhere herein. In some instances, the sequence of the protein fragment is further determined. In some instances, the protein fragment correlates to a small molecule fragment binding site on the cysteine containing protein. 
     In some embodiments, the sequence of the protein fragment correlates to a sequence as illustrated in Tables 1-3 or 8-9. In some instances, the sequence as shown in Tables 1-3 or 8-9 correlate to a site on the full length protein as a drug binding site. In some instances, the sequence as shown in Tables 1-3 or 8-9 correlate to a drug binding site. In some instances, polypeptides comprising one or more of the sequences as shown in Tables 1-3 or 8-9 serve as probes for small molecule fragment screening. 
     In some instances after the generation of a polypeptide, the polypeptide is subjected to one or more rounds of purification steps to remove impurities. In some instances, the purification step is a chromatographic step utilizing separation methods such as affinity-based, size-exclusion based, ion-exchange based, or the like. In some cases, the polypeptide is at most 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95%, 99%, 99.9%, or 100% pure or without the presence of impurities. In some cases, the polypeptide is at least 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95%, 99%, 99.9%, or 100% pure or without the presence of impurities. 
     As described above, nucleic acid encoding a polypeptide that is derived from a cysteine containing protein is subjected to one or more rounds of purification steps to remove impurities. In some instances, the purification step is a chromatographic step utilizing separation methods such as affinity-based, size-exclusion based, ion-exchange based, or the like. In some cases, the nucleic acid is at most 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95%, 99%, 99.9%, or 100% pure or without the presence of impurities. In some cases, the nucleic acid is at least 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95%, 99%, 99.9%, or 100% pure or without the presence of impurities. 
     As used herein, a polypeptide includes natural amino acids, unnatural amino acids, or a combination thereof. In some instances, an amino acid residue refers to a molecule containing both an amino group and a carboxyl group. Suitable amino acids include, without limitation, both the D- and L-isomers of the naturally-occurring amino acids, as well as non-naturally occurring amino acids prepared by organic synthesis or other metabolic routes. The term amino acid, as used herein, includes, without limitation, α-amino acids, natural amino acids, non-natural amino acids, and amino acid analogs. 
     The term “α-amino acid” refers to a molecule containing both an amino group and a carboxyl group bound to a carbon which is designated the α-carbon. 
     The term “β-amino acid” refers to a molecule containing both an amino group and a carboxyl group in a β configuration. 
     “Naturally occurring amino acid” refers to any one of the twenty amino acids commonly found in peptides synthesized in nature, and known by the one letter abbreviations A, R, N, C, D, Q, E, G, H, I, L, K, M, F, P, S, T, W, Y and V. 
     The following table shows a summary of the properties of natural amino acids: 
     
       
         
           
               
               
               
               
               
               
             
               
                   
               
               
                   
                 3- 
                 1- 
                 Side- 
                 Side-chain 
                   
               
               
                   
                 Letter 
                 Letter 
                 chain 
                 charge 
                 Hydropathy 
               
               
                 Amino Acid 
                 Code 
                 Code 
                 Polarity 
                 (pH 7.4) 
                 Index 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
               
               
            
               
                 Alanine 
                 Ala 
                 A 
                 nonpolar 
                 neutral 
                 1.8 
               
               
                 Arginine 
                 Arg 
                 R 
                 polar 
                 positive 
                 −4.5 
               
               
                 Asparagine 
                 Asn 
                 N 
                 polar 
                 neutral 
                 −3.5 
               
               
                 Aspartic acid 
                 Asp 
                 D 
                 polar 
                 negative 
                 −3.5 
               
               
                 Cysteine 
                 Cys 
                 C 
                 polar 
                 neutral 
                 2.5 
               
               
                 Glutamic acid 
                 Glu 
                 E 
                 polar 
                 negative 
                 −3.5 
               
               
                 Glutamine 
                 Gln 
                 Q 
                 polar 
                 neutral 
                 −3.5 
               
               
                 Glycine 
                 Gly 
                 G 
                 nonpolar 
                 neutral 
                 −0.4 
               
               
                 Histidine 
                 His 
                 H 
                 polar 
                 positive(10%) 
                 −3.2 
               
               
                   
                   
                   
                   
                 neutral(90%) 
                   
               
               
                 Isoleucine 
                 Ile 
                 I 
                 nonpolar 
                 neutral 
                 4.5 
               
               
                 Leucine 
                 Leu 
                 L 
                 nonpolar 
                 neutral 
                 3.8 
               
               
                 Lysine 
                 Lys 
                 K 
                 polar 
                 positive 
                 −3.9 
               
               
                 Methionine 
                 Met 
                 M 
                 nonpolar 
                 neutral 
                 1.9 
               
               
                 Phenylalanine 
                 Phe 
                 F 
                 nonpolar 
                 neutral 
                 2.8 
               
               
                 Proline 
                 Pro 
                 P 
                 nonpolar 
                 neutral 
                 −1.6 
               
               
                 Serine 
                 Ser 
                 S 
                 polar 
                 neutral 
                 −0.8 
               
               
                 Threonine 
                 Thr 
                 T 
                 polar 
                 neutral 
                 −0.7 
               
               
                 Tryptophan 
                 Trp 
                 W 
                 nonpolar 
                 neutral 
                 −0.9 
               
               
                 Tyrosine 
                 Tyr 
                 Y 
                 polar 
                 neutral 
                 −1.3 
               
               
                 Valine 
                 Val 
                 V 
                 nonpolar 
                 neutral 
                 4.2 
               
               
                   
               
            
           
         
       
     
     “Hydrophobic amino acids” include small hydrophobic amino acids and large hydrophobic amino acids. “Small hydrophobic amino acid” are glycine, alanine, proline, and analogs thereof. “Large hydrophobic amino acids” are valine, leucine, isoleucine, phenylalanine, methionine, tryptophan, and analogs thereof. “Polar amino acids” are serine, threonine, asparagine, glutamine, cysteine, tyrosine, and analogs thereof. “Charged amino acids” are lysine, arginine, histidine, aspartate, glutamate, and analogs thereof. In some cases, aspartic acid and glutamic acid are referred to as acidic amino acids. In other cases, lysine, arginine and histidine are referred to as basic amino acids. 
     The term “amino acid analog” refers to a molecule which is structurally similar to an amino acid and which is substituted for an amino acid in the formation of a peptidomimetic macrocycle Amino acid analogs include, without limitation, β-amino acids and amino acids where the amino or carboxy group is substituted by a similarly reactive group (e.g., substitution of the primary amine with a secondary or tertiary amine, or substitution of the carboxy group with an ester). 
     The term “non-natural amino acid” refers to an amino acid which is not one of the twenty amino acids commonly found in peptides synthesized in nature, and known by the one letter abbreviations A, R, N, C, D, Q, E, G, H, I, L, K, M, F, P, S, T, W Y and V. 
     In some instances, amino acid analogs include β-amino acid analogs. Examples of β-amino acid analogs include, but are not limited to, the following: cyclic β-amino acid analogs; β-alanine; (R)-β-phenylalanine; (R)-1,2,3,4-tetrahydro-isoquinoline-3-acetic acid; (R)-3-amino-4-(1-naphthyl)-butyric acid; (R)-3-amino-4-(2,4-dichlorophenyl)butyric acid; (R)-3-amino-4-(2-chlorophenyl)-butyric acid; (R)-3-amino-4-(2-cyanophenyl)-butyric acid; (R)-3-amino-4-(2-fluorophenyl)-butyric acid; (R)-3-amino-4-(2-furyl)-butyric acid; (R)-3-amino-4-(2-methylphenyl)-butyric acid; (R)-3-amino-4-(2-naphthyl)-butyric acid; (R)-3-amino-4-(2-thienyl)-butyric acid; (R)-3-amino-4-(2-trifluoromethylphenyl)-butyric acid; (R)-3-amino-4-(3,4-dichlorophenyl)butyric acid; (R)-3-amino-4-(3,4-difluorophenyl)butyric acid; (R)-3-amino-4-(3-benzothienyl)-butyric acid; (R)-3-amino-4-(3-chlorophenyl)-butyric acid; (R)-3-amino-4-(3-cyanophenyl)-butyric acid; (R)-3-amino-4-(3-fluorophenyl)-butyric acid; (R)-3-amino-4-(3-methylphenyl)-butyric acid; (R)-3-amino-4-(3-pyridyl)-butyric acid; (R)-3-amino-4-(3-thienyl)-butyric acid; (R)-3-amino-4-(3-trifluoromethylphenyl)-butyric acid; (R)-3-amino-4-(4-bromophenyl)-butyric acid; (R)-3-amino-4-(4-chlorophenyl)-butyric acid; (R)-3-amino-4-(4-cyanophenyl)-butyric acid; (R)-3-amino-4-(4-fluorophenyl)-butyric acid; (R)-3-amino-4-(4-iodophenyl)-butyric acid; (R)-3-amino-4-(4-methylphenyl)-butyric acid; (R)-3-amino-4-(4-nitrophenyl)-butyric acid; (R)-3-amino-4-(4-pyridyl)-butyric acid; (R)-3-amino-4-(4-trifluoromethylphenyl)-butyric acid; (R)-3-amino-4-pentafluoro-phenylbutyric acid; (R)-3-amino-5-hexenoic acid; (R)-3-amino-5-hexynoic acid; (R)-3-amino-5-phenylpentanoic acid; (R)-3-amino-6-phenyl-5-hexenoic acid; (S)-1,2,3,4-tetrahydro-isoquinoline-3-acetic acid; (S)-3-amino-4-(1-naphthyl)-butyric acid; (S)-3-amino-4-(2,4-dichlorophenyl)butyric acid; (S)-3-amino-4-(2-chlorophenyl)-butyric acid; (S)-3-amino-4-(2-cyanophenyl)-butyric acid; (S)-3-amino-4-(2-fluorophenyl)-butyric acid; (S)-3-amino-4-(2-furyl)-butyric acid; (S)-3-amino-4-(2-methylphenyl)-butyric acid; (S)-3-amino-4-(2-naphthyl)-butyric acid; (S)-3-amino-4-(2-thienyl)-butyric acid; (S)-3-amino-4-(2-trifluoromethylphenyl)-butyric acid; (S)-3-amino-4-(3,4-dichlorophenyl)butyric acid; (S)-3-amino-4-(3,4-difluorophenyl)butyric acid; (S)-3-amino-4-(3-benzothienyl)-butyric acid; (S)-3-amino-4-(3-chlorophenyl)-butyric acid; (S)-3-amino-4-(3-cyanophenyl)-butyric acid; (S)-3-amino-4-(3-fluorophenyl)-butyric acid; (S)-3-amino-4-(3-methylphenyl)-butyric acid; (S)-3-amino-4-(3-pyridyl)-butyric acid; (S)-3-amino-4-(3-thienyl)-butyric acid; (S)-3-amino-4-(3-trifluoromethylphenyl)-butyric acid; (S)-3-amino-4-(4-bromophenyl)-butyric acid; (S)-3-amino-4-(4-chlorophenyl) butyric acid; (S)-3-amino-4-(4-cyanophenyl)-butyric acid; (S)-3-amino-4-(4-fluorophenyl) butyric acid; (S)-3-amino-4-(4-iodophenyl)-butyric acid; (S)-3-amino-4-(4-methylphenyl)-butyric acid; (S)-3-amino-4-(4-nitrophenyl)-butyric acid; (S)-3-amino-4-(4-pyridyl)-butyric acid; (S)-3-amino-4-(4-trifluoromethylphenyl)-butyric acid; (S)-3-amino-4-pentafluoro-phenylbutyric acid; (S)-3-amino-5-hexenoic acid; (S)-3-amino-5-hexynoic acid; (S)-3-amino-5-phenylpentanoic acid; (S)-3-amino-6-phenyl-5-hexenoic acid; 1,2,5,6-tetrahydropyridine-3-carboxylic acid; 1,2,5,6-tetrahydropyridine-4-carboxylic acid; 3-amino-3-(2-chlorophenyl)-propionic acid; 3-amino-3-(2-thienyl)-propionic acid; 3-amino-3-(3-bromophenyl)-propionic acid; 3-amino-3-(4-chlorophenyl)-propionic acid; 3-amino-3-(4-methoxyphenyl)-propionic acid; 3-amino-4,4,4-trifluoro-butyric acid; 3-aminoadipic acid; D-β-phenylalanine; β-leucine; L-β-homoalanine; L-β-homoaspartic acid γ-benzyl ester; L-β-homoglutamic acid δ-benzyl ester; L-β-homoisoleucine; L-β-homoleucine; L-β-homomethionine; L-β-homophenylalanine; L-β-homoproline; L-β-homotryptophan; L-β-homovaline; L-Nω-benzyloxycarbony-β-homolysine; Nω-L-β-homoarginine; O-benzyl-L-β-homohydroxyproline; O-benzyl-L-β-homoserine; O-benzyl-L-β-homothreonine; O-benzyl-L-β-homotyrosine; γ-trityl-L-β-homoasparagine; (R)-β-phenylalanine; L-β-homoaspartic acid γ-t-butyl ester; L-β-homoglutamic acid δ-t-butyl ester; L-Nω-β-homolysine; Nδ-trityl-L-β-homoglutamine; Nω-2,2,4,6,7-pentamethyl-dihydrobenzofuran-5-sulfonyl-L-3-homoarginine; O-t-butyl-L-β-homohydroxyproline; O-t-butyl-L-β-homoserine; O-t-butyl-L-β-homothreonine; O-t-butyl-L-β-homotyrosine; 2-aminocyclopentane carboxylic acid; and 2-aminocyclohexane carboxylic acid. 
     In some instances, amino acid analogs include analogs of alanine, valine, glycine or leucine. Examples of amino acid analogs of alanine, valine, glycine, and leucine include, but are not limited to, the following: α-methoxyglycine; α-allyl-L-alanine; α-aminoisobutyric acid; α-methyl-leucine; β-(1-naphthyl)-D-alanine; β-(1-naphthyl)-L-alanine; β-(2-naphthyl)-D-alanine; β-(2-naphthyl)-L-alanine; β-(2-pyridyl)-D-alanine β-(2-pyridyl)-L-alanine; β-(2-thienyl)-D-alanine; β-(2-thienyl)-L-alanine; β-(3-benzothienyl)-D-alanine; β-(3-benzothienyl)-L-alanine; β-(3-pyridyl)-D-alanine; β-(3-pyridyl)-L-alanine; β-(4-pyridyl)-D-alanine; β-(4-pyridyl)-L-alanine; β-chloro-L-alanine; β-cyano-L-alanin; β-cyclohexyl-D-alanine; β-cyclohexyl-L-alanine; β-cyclopenten-1-yl-alanine; β-cyclopentyl-alanine; β-cyclopropyl-L-Ala-OH.dicyclohexylammonium salt; β-t-butyl-D-alanine; β-t-butyl-L-alanine; γ-aminobutyric acid; L-α,β-diaminopropionic acid; 2,4-dinitro-phenylglycine; 2,5-dihydro-D-phenylglycine; 2-amino-4,4,4-trifluorobutyric acid; 2-fluoro-phenylglycine; 3-amino-4,4,4-trifluoro-butyric acid; 3-fluoro-valine; 4,4,4-trifluoro-valine; 4,5-dehydro-L-leu-OH.dicyclohexylammonium salt; 4-fluoro-D-phenylglycine; 4-fluoro-L-phenylglycine; 4-hydroxy-D-phenylglycine; 5,5,5-trifluoro-leucine; 6-aminohexanoic acid; cyclopentyl-D-Gly-OH.dicyclohexylammonium salt; cyclopentyl-Gly-OH.dicyclohexylammonium salt; D-α,β-diaminopropionic acid; D-α-aminobutyric acid; D-α-t-butylglycine; D-(2-thienyl)glycine; D-(3-thienyl)glycine; D-2-aminocaproic acid; D-2-indanylglycine; D-allylglycine-dicyclohexylammonium salt; D-cyclohexylglycine; D-norvaline; D-phenylglycine; β-aminobutyric acid; β-aminoisobutyric acid; (2-bromophenyl)glycine; (2-methoxyphenyl)glycine; (2-methylphenyl)glycine; (2-thiazoyl)glycine; (2-thienyl)glycine; 2-amino-3-(dimethylamino)-propionic acid; L-α,β-diaminopropionic acid; L-α-aminobutyric acid; L-α-t-butylglycine; L-(3-thienyl)glycine; L-2-amino-3-(dimethylamino)-propionic acid; L-2-aminocaproic acid dicyclohexyl-ammonium salt; L-2-indanylglycine; L-allylglycine.dicyclohexyl ammonium salt; L-cyclohexylglycine; L-phenylglycine; L-propargylglycine; L-norvaline; N-α-aminomethyl-L-alanine; D-α,γ-diaminobutyric acid; L-α,γ-diaminobutyric acid; β-cyclopropyl-L-alanine; (N-β-(2,4-dinitrophenyl))-L-α,β-diaminopropionic acid; (N-β-1-(4,4-dimethyl-2,6-dioxocyclohex-1-ylidene)ethyl)-D-α,4-diaminopropionic acid; (N-β-1-(4,4-dimethyl-2,6-dioxocyclohex-1-ylidene)ethyl)-L-α,β-diaminopropionic acid; (N-β-4-methyltrityl)-L-α,β-diaminopropionic acid; (N-β-allyloxycarbonyl)-L-α,β-diaminopropionic acid; (N-γ-1-(4,4-dimethyl-2,6-dioxocyclohex-1-ylidene)ethyl)-D-α,γ-diaminobutyric acid; (N-γ-1-(4,4-dimethyl-2,6-dioxocyclohex-1-ylidene)ethyl)-L-α,γ-diaminobutyric acid; (N-γ-4-methyltrityl)-D-α,γ-diaminobutyric acid; (N-γ-4-methyltrityl)-L-α,γ-diaminobutyric acid; (N-γ-allyloxycarbonyl)-L-α,γ-diaminobutyric acid; D-α,γ-diaminobutyric acid; 4,5-dehydro-L-leucine; cyclopentyl-D-Gly-OH; cyclopentyl-Gly-OH; D-allylglycine; D-homocyclohexylalanine; L-1-pyrenylalanine; L-2-aminocaproic acid; L-allylglycine; L-homocyclohexylalanine; and N-(2-hydroxy-4-methoxy-Bzl)-Gly-OH. 
     In some instances, amino acid analogs include analogs of arginine or lysine. Examples of amino acid analogs of arginine and lysine include, but are not limited to, the following: citrulline; L-2-amino-3-guanidinopropionic acid; L-2-amino-3-ureidopropionic acid; L-citrulline; Lys(Me) 2 -OH; Lys(N 3 )—OH; Nδ-benzyloxycarbonyl-L-omithine; Nω-nitro-D-arginine; Nω-nitro-L-arginine; α-methyl-omithine; 2,6-diaminoheptanedioic acid; L-omithine; (Nδ-1-(4,4-dimethyl-2,6-dioxo-cyclohex-1-ylidene)ethyl)-D-omithine; (Nδ-1-(4,4-dimethyl-2,6-dioxo-cyclohex-1-ylidene)ethyl)-L-omithine; (Nδ-4-methyltrityl)-D-omithine; (Nδ-4-methyltrityl)-L-omithine; D-omithine; L-omithine; Arg(Me)(Pbf)-OH; Arg(Me) 2 -OH (asymmetrical); Arg(Me)2-OH (symmetrical); Lys(ivDde)-OH; Lys(Me)2-OH.HCl; Lys(Me3)-OH chloride; Nω-nitro-D-arginine; and Nω-nitro-L-arginine. 
     In some instances, amino acid analogs include analogs of aspartic or glutamic acids. Examples of amino acid analogs of aspartic and glutamic acids include, but are not limited to, the following: α-methyl-D-aspartic acid; α-methyl-glutamic acid; α-methyl-L-aspartic acid; γ-methylene-glutamic acid; (N-γ-ethyl)-L-glutamine; [N-α-(4-aminobenzoyl)]-L-glutamic acid; 2,6-diaminopimelic acid; L-α-aminosuberic acid; D-2-aminoadipic acid; D-α-aminosuberic acid; α-aminopimelic acid; iminodiacetic acid; L-2-aminoadipic acid; threo-β-methyl-aspartic acid; γ-carboxy-D-glutamic acid γ,γ-di-t-butyl ester; γ-carboxy-L-glutamic acid γ,γ-di-t-butyl ester; Glu(OAll)-OH; L-Asu(OtBu)-OH; and pyroglutamic acid. 
     In some instances, amino acid analogs include analogs of cysteine and methionine. Examples of amino acid analogs of cysteine and methionine include, but are not limited to, Cys(farnesyl)-OH, Cys(farnesyl)-OMe, α-methyl-methionine, Cys(2-hydroxyethyl)-OH, Cys(3-aminopropyl)-OH, 2-amino-4-(ethylthio)butyric acid, buthionine, buthioninesulfoximine, ethionine, methionine methylsulfonium chloride, selenomethionine, cysteic acid, [2-(4-pyridyl)ethyl]-DL-penicillamine, [2-(4-pyridyl)ethyl]-L-cysteine, 4-methoxybenzyl-D-penicillamine, 4-methoxybenzyl-L-penicillamine, 4-methylbenzyl-D-penicillamine, 4-methylbenzyl-L-penicillamine, benzyl-D-cysteine, benzyl-L-cysteine, benzyl-DL-homocysteine, carbamoyl-L-cysteine, carboxyethyl-L-cysteine, carboxymethyl-L-cysteine, diphenylmethyl-L-cysteine, ethyl-L-cysteine, methyl-L-cysteine, t-butyl-D-cysteine, trityl-L-homocysteine, trityl-D-penicillamine, cystathionine, homocystine, L-homocystine, (2-aminoethyl)-L-cysteine, seleno-L-cystine, cystathionine, Cys(StBu)-OH, and acetamidomethyl-D-penicillamine. 
     In some instances, amino acid analogs include analogs of phenylalanine and tyrosine. Examples of amino acid analogs of phenylalanine and tyrosine include β-methyl-phenylalanine, β-hydroxyphenylalanine, α-methyl-3-methoxy-DL-phenylalanine, α-methyl-D-phenylalanine, α-methyl-L-phenylalanine, 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid, 2,4-dichloro-phenylalanine, 2-(trifluoromethyl)-D-phenylalanine, 2-(trifluoromethyl)-L-phenylalanine, 2-bromo-D-phenylalanine, 2-bromo-L-phenylalanine, 2-chloro-D-phenylalanine, 2-chloro-L-phenylalanine, 2-cyano-D-phenylalanine, 2-cyano-L-phenylalanine, 2-fluoro-D-phenylalanine, 2-fluoro-L-phenylalanine, 2-methyl-D-phenylalanine, 2-methyl-L-phenylalanine, 2-nitro-D-phenylalanine, 2-nitro-L-phenylalanine, 2;4;5-trihydroxy-phenylalanine, 3,4,5-trifluoro-D-phenylalanine, 3,4,5-trifluoro-L-phenylalanine, 3,4-dichloro-D-phenylalanine, 3,4-dichloro-L-phenylalanine, 3,4-difluoro-D-phenylalanine, 3,4-difluoro-L-phenylalanine, 3,4-dihydroxy-L-phenylalanine, 3,4-dimethoxy-L-phenylalanine, 3,5,3′-triiodo-L-thyronine, 3,5-diiodo-D-tyrosine, 3,5-diiodo-L-tryosine, 3,5-diiodo-L-thyronine, 3-(trifluoromethyl)-D-phenylalanine, 3-(trifluoromethyl)-L-phenylalanine, 3-amino-L-tyrosine, 3-bromo-D-phenylalanine, 3-bromo-L-phenylalanine, 3-chloro-D-phenylalanine, 3-chloro-L-phenylalanine, 3-chloro-L-tyrosine, 3-cyano-D-phenylalanine, 3-cyano-L-phenylalanine, 3-fluoro-D-phenylalanine, 3-fluoro-L-phenylalanine, 3-fluoro-tyrosine, 3-iodo-D-phenylalanine, 3-iodo-L-phenylalanine, 3-iodo-L-tyrosine, 3-methoxy-L-tyrosine, 3-methyl-D-phenylalanine, 3-methyl-L-phenylalanine, 3-nitro-D-phenylalanine, 3-nitro-L-phenylalanine, 3-nitro-L-tyrosine, 4-(trifluoromethyl)-D-phenylalanine, 4-(trifluoromethyl)-L-phenylalanine, 4-amino-D-phenylalanine, 4-amino-L-phenylalanine, 4-benzoyl-D-phenylalanine, 4-benzoyl-L-phenylalanine, 4-bis(2-chloroethyl)amino-L-phenylalanine, 4-bromo-D-phenylalanine, 4-bromo-L-phenylalanine, 4-chloro-D-phenylalanine, 4-chloro-L-phenylalanine, 4-cyano-D-phenylalanine, 4-cyano-L-phenylalanine, 4-fluoro-D-phenylalanine, 4-fluoro-L-phenylalanine, 4-iodo-D-phenylalanine, 4-iodo-L-phenylalanine, homophenylalanine, thyroxine, 3,3-diphenylalanine, thyronine, ethyl-tryosine, and methyl-tyrosine. 
     In some instances, amino acid analogs include analogs of proline. Examples of amino acid analogs of proline include, but are not limited to, 3,4-dehydro-proline, 4-fluoro-proline, cis-4-hydroxy-proline, thiazolidine-2-carboxylic acid, and trans-4-fluoro-proline. 
     In some instances, amino acid analogs include analogs of serine and threonine. Examples of amino acid analogs of serine and threonine include, but are not limited to, 3-amino-2-hydroxy-5-methylhexanoic acid, 2-amino-3-hydroxy-4-methylpentanoic acid, 2-amino-3-ethoxybutanoic acid, 2-amino-3-methoxybutanoic acid, 4-amino-3-hydroxy-6-methylheptanoic acid, 2-amino-3-benzyloxypropionic acid, 2-amino-3-benzyloxypropionic acid, 2-amino-3-ethoxypropionic acid, 4-amino-3-hydroxybutanoic acid, and α-methylserine. 
     In some instances, amino acid analogs include analogs of tryptophan. Examples of amino acid analogs of tryptophan include, but are not limited to, the following: α-methyl-tryptophan; β-(3-benzothienyl)-D-alanine; β-(3-benzothienyl)-L-alanine; 1-methyl-tryptophan; 4-methyl-tryptophan; 5-benzyloxy-tryptophan; 5-bromo-tryptophan; 5-chloro-tryptophan; 5-fluoro-tryptophan; 5-hydroxy-tryptophan, 5-hydroxy-L-tryptophan; 5-methoxy-tryptophan; 5-methoxy-L-tryptophan; 5-methyl-tryptophan; 6-bromo-tryptophan; 6-chloro-D-tryptophan; 6-chloro-tryptophan; 6-fluoro-tryptophan; 6-methyl-tryptophan; 7-benzyloxy-tryptophan; 7-bromo-tryptophan; 7-methyl-tryptophan; D-1,2,3,4-tetrahydro-norharman-3-carboxylic acid; 6-methoxy-1,2,3,4-tetrahydronorharman-1-carboxylic acid; 7-azatryptophan; L-1,2,3,4-tetrahydro-norharman-3-carboxylic acid; 5-methoxy-2-methyl-tryptophan; and 6-chloro-L-tryptophan. 
     In some instances, amino acid analogs are racemic. In some instances, the D isomer of the amino acid analog is used. In some cases, the L isomer of the amino acid analog is used. In some instances, the amino acid analog comprises chiral centers that are in the R or S configuration. Sometimes, the amino group(s) of a β-amino acid analog is substituted with a protecting group, e.g., tert-butyloxycarbonyl (BOC group), 9-fluorenylmethyloxycarbonyl (FMOC), tosyl, and the like. Sometimes, the carboxylic acid functional group of a β-amino acid analog is protected, e.g., as its ester derivative. In some cases, the salt of the amino acid analog is used. 
     In some embodiments, nucleic acid molecules refer to at least two nucleotides covalently linked together. In some instances, a nucleic acid described herein contains phosphodiester bonds, although in some cases, as outlined below (for example in the construction of primers and probes such as label probes), nucleic acid analogs are included that have alternate backbones, comprising, for example, phosphoramide (Beaucage et al., Tetrahedron 49(10): 1925 (1993) and references therein; Letsinger, J. Org. Chem. 35:3800 (1970); Sprinzl et al., Eur. J. Biochem. 81:579 (1977); Letsinger et al., Nucl. Acids Res. 14:3487 (1986); Sawai et al, Chem. Lett. 805 (1984), Letsinger et al., J. Am. Chem. Soc. 110:4470 (1988); and Pauwels et al., Chemica Scripta 26:141 91986)), phosphorothioate (Mag et al., Nucleic Acids Res. 19:1437 (1991); and U.S. Pat. No. 5,644,048), phosphorodithioate (Bnu et al., J. Am. Chem. Soc. 111:2321 (1989), O-methylphosphoroamidite linkages (see Eckstein, Oligonucleotides and Analogues: A Practical Approach, Oxford University Press), and peptide nucleic acid (also referred to herein as “PNA”) backbones and linkages (see Egholm, J. Am. Chem. Soc. 114:1895 (1992); Meier et al., Chem. Int. Ed. Engl, 31:1008 (1992); Nielsen, Nature, 365:566 (1993): Carlsson et al., Nature 380:207 (1996), all of which are incorporated by reference). Other analog nucleic acids include those with bicyclic structures including locked nucleic acids (also referred to herein as “LNA”), Koshkin et al., J. Am. Chem. Soc. 120.13252 3 (1998); positive backbones (Denpcy et al., Proc. Natl. Acad. Sci. USA 92:6097 (1995); non-ionic backbones (U.S. Pat. Nos. 5,386,023, 5,637,684, 5,602,240, 5,216,141 and 4,469,863; Kiedrowshi et al., Angew. Chem. Intl. Ed. English 30:423 (1991); Letsinger et al., J. Am. Chem. Soc. 110:4470 (1988): Letsinger et al., Nucleoside &amp;amp; Nucleotide 13:1597 (1994); Chapters 2 and 3, ASC Symposium Series 580, “Carbohydrate Modifications in Antisense Research”, Ed. Y. S. Sanghui and P. Dan Cook; Mesmaeker et al., Bioorganic &amp; Medicinal Chem. Lett. 4:395 (1994); Jeffs et al., J. Biomolecular NMR 34:17 (1994); Tetrahedron Lett. 37:743 (1996)) and non-ribose backbones, including those described in U.S. Pat. Nos. 5,235,033 and 5,034,506, and Chapters 6 and 7, ASC Symposium Series 580, “Carbohydrate Modifications in Antisense Research”, Ed. Y. S. Sanghui and P. Dan Cook. Nucleic acids containing one or more carbocyclic sugars are also included within the definition of nucleic acids (see Jenkins et al., Chem. Soc. Rev. (1995) pp 169 176). Several nucleic acid analogs are described in Rawls, C &amp; E News Jun. 2, 1997 page 35. “Locked nucleic acids” are also included within the definition of nucleic acid analogs. LNAs are a class of nucleic acid analogues in which the ribose ring is “locked” by a methylene bridge connecting the 2′-O atom with the 4′-C atom. All of these references are hereby expressly incorporated by reference. In some instances, these modifications of the ribose-phosphate backbone are done to increase the stability and half-life of such molecules in physiological environments. For example, PNA:DNA and LNA-DNA hybrids exhibit higher stability and thus are used in some embodiments. The target nucleic acids are single stranded or double stranded, as specified, or contain portions of both double stranded or single stranded sequence. Depending on the application, the nucleic acids are DNA (including, e.g., genomic DNA, mitochondrial DNA, and cDNA), RNA (including, e.g., mRNA and rRNA) or a hybrid, where the nucleic acid contains any combination of deoxyribo- and ribo-nucleotides, and any combination of bases, including uracil, adenine, thymine, cytosine, guanine, inosine, xathanine hypoxathanine, isocytosine, isoguanine, etc. 
     Samples, Analytical Techniques, and Instrumentation 
     In certain embodiments, one or more of the methods disclosed herein comprise a sample. In some embodiments, the sample is a cell sample or a tissue sample. In some instances, the sample is a cell sample. In some embodiments, the sample for use with the methods described herein is obtained from cells of an animal. In some instances, the animal cell includes a cell from a marine invertebrate, fish, insects, amphibian, reptile, or mammal. In some instances, the mammalian cell is a primate, ape, equine, bovine, porcine, canine, feline, or rodent. In some instances, the mammal is a primate, ape, dog, cat, rabbit, ferret, or the like. In some cases, the rodent is a mouse, rat, hamster, gerbil, hamster, chinchilla, or guinea pig. In some embodiments, the bird cell is from a canary, parakeet or parrots. In some embodiments, the reptile cell is from a turtles, lizard or snake. In some cases, the fish cell is from a tropical fish. In some cases, the fish cell is from a zebrafish (e.g.  Danino rerio ). In some cases, the worm cell is from a nematode (e.g.  C. elegans ). In some cases, the amphibian cell is from a frog. In some embodiments, the arthropod cell is from a tarantula or hermit crab. 
     In some embodiments, the sample for use with the methods described herein is obtained from a mammalian cell. In some instances, the mammalian cell is an epithelial cell, connective tissue cell, hormone secreting cell, a nerve cell, a skeletal muscle cell, a blood cell, or an immune system cell. 
     Exemplary mammalian cells include, but are not limited to, 293A cell line, 293FT cell line, 293F cells, 293 H cells, HEK 293 cells, CHO DG44 cells, CHO-S cells, CHO-K1 cells, Expi293F™ cells, Flp-In™ T-REx™ 293 cell line, Flp-In™-293 cell line, Flp-In™-3T3 cell line, Flp-In™-BHK cell line, Flp-In™-CHO cell line, Flp-In™-CV-1 cell line, Flp-In™-Jurkat cell line, FreeStyle™ 293-F cells, FreeStyle™ CHO-S cells, GripTite™ 293 MSR cell line, GS-CHO cell line, HepaRG™ cells, T-REx™ Jurkat cell line, Per.C6 cells, T-REx™-293 cell line, T-REx™-CHO cell line, T-REx™-HeLa cell line, NC-HIMT cell line, and PC12 cell line. 
     In some instances, the sample for use with the methods described herein is obtained from cells of a tumor cell line. In some instances, the sample is obtained from cells of a solid tumor cell line. In some instances, the solid tumor cell line is a sarcoma cell line. In some instances, the solid tumor cell line is a carcinoma cell line. In some embodiments, the sarcoma cell line is obtained from a cell line of alveolar rhabdomyosarcoma, alveolar soft part sarcoma, ameloblastoma, angiosarcoma, chondrosarcoma, chordoma, clear cell sarcoma of soft tissue, dedifferentiated liposarcoma, desmoid, desmoplastic small round cell tumor, embryonal rhabdomyosarcoma, epithelioid fibrosarcoma, epithelioid hemangioendothelioma, epithelioid sarcoma, esthesioneuroblastoma, Ewing sarcoma, extrarenal rhabdoid tumor, extraskeletal myxoid chondrosarcoma, extraskeletal osteosarcoma, fibrosarcoma, giant cell tumor, hemangiopericytoma, infantile fibrosarcoma, inflammatory myofibroblastic tumor, Kaposi sarcoma, leiomyosarcoma of bone, liposarcoma, liposarcoma of bone, malignant fibrous histiocytoma (MFH), malignant fibrous histiocytoma (MFH) of bone, malignant mesenchymoma, malignant peripheral nerve sheath tumor, mesenchymal chondrosarcoma, myxofibrosarcoma, myxoid liposarcoma, myxoinflammatory fibroblastic sarcoma, neoplasms with perivascular epitheioid cell differentiation, osteosarcoma, parosteal osteosarcoma, neoplasm with perivascular epitheioid cell differentiation, periosteal osteosarcoma, pleomorphic liposarcoma, pleomorphic rhabdomyosarcoma, PNET/extraskeletal Ewing tumor, rhabdomyosarcoma, round cell liposarcoma, small cell osteosarcoma, solitary fibrous tumor, synovial sarcoma, telangiectatic osteosarcoma. 
     In some embodiments, the carcinoma cell line is obtained from a cell line of adenocarcinoma, squamous cell carcinoma, adenosquamous carcinoma, anaplastic carcinoma, large cell carcinoma, small cell carcinoma, anal cancer, appendix cancer, bile duct cancer (i.e., cholangiocarcinoma), bladder cancer, brain tumor, breast cancer, cervical cancer, colon cancer, cancer of Unknown Primary (CUP), esophageal cancer, eye cancer, fallopian tube cancer, gastroenterological cancer, kidney cancer, liver cancer, lung cancer, medulloblastoma, melanoma, oral cancer, ovarian cancer, pancreatic cancer, parathyroid disease, penile cancer, pituitary tumor, prostate cancer, rectal cancer, skin cancer, stomach cancer, testicular cancer, throat cancer, thyroid cancer, uterine cancer, vaginal cancer, or vulvar cancer. 
     In some instances, the sample is obtained from cells of a hematologic malignant cell line. In some instances, the hematologic malignant cell line is a T-cell cell line. In some instances, B-cell cell line. In some instances, the hematologic malignant cell line is obtained from a T-cell cell line of: peripheral T-cell lymphoma not otherwise specified (PTCL-NOS), anaplastic large cell lymphoma, angioimmunoblastic lymphoma, cutaneous T-cell lymphoma, adult T-cell leukemia/lymphoma (ATLL), blastic NK-cell lymphoma, enteropathy-type T-cell lymphoma, hematosplenic gamma-delta T-cell lymphoma, lymphoblastic lymphoma, nasal NK/T-cell lymphomas, or treatment-related T-cell lymphomas. 
     In some instances, the hematologic malignant cell line is obtained from a B-cell cell line of: acute lymphoblastic leukemia (ALL), acute myelogenous leukemia (AML), chronic myelogenous leukemia (CML), acute monocytic leukemia (AMoL), chronic lymphocytic leukemia (CLL), high-risk chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), high-risk small lymphocytic lymphoma (SLL), follicular lymphoma (FL), mantle cell lymphoma (MCL), Waldenstrom&#39;s macroglobulinemia, multiple myeloma extranodal marginal zone B cell lymphoma, nodal marginal zone B cell lymphoma. Burkitt&#39;s lymphoma, non-Burkitt high grade B cell lymphoma, primary mediastinal B-cell lymphoma (PMBL), immunoblastic large cell lymphoma, precursor B-lymphoblastic lymphoma. B cell prolymphocytic leukemia, lymphoplasmacytic lymphoma, splenic marginal zone lymphoma, plasma cell myeloma, plasmacytoma, mediastinal (thymic) large B cell lymphoma, intravascular large B cell lymphoma, primary effusion lymphoma, or lymphomatoid granulomatosis. 
     In some embodiments, the sample for use with the methods described herein is obtained from a tumor cell line. Exemplary tumor cell line includes, but is not limited to, 600MPE, AU565, BT-20, BT-474, BT-483, BT-549, Evsa-T, Hs578T, MCF-7, MDA-MB-231, SkBr3, T-47D, HeLa, DU 145, PC3, LNCaP, A549, H1299, NCI-H460, A2780, SKOV-3/Luc, Neuro2a, RKO, RKO-AS45-1. HT-29, SW1417, SW948, DLD-1, SW480, Capan-1, MC/9, B72.3, B25.2, B6.2, B38.1, DMS153, SU.86.86, SNU-182, SNU-423, SNU-449, SNU-475, SNU-387, Hs 817.T, LMH, LMH/2A, SNU-398, PLHC-1, HepG2/SF, OCI-Ly1, OCI-Ly2, OCI-Ly3, OCI-Ly4, OCI-Ly6, OCI-Ly7, OCI-Ly10, OCI-Ly18, OCI-Ly19, U2932, DB, HBL-1, RIVA, SUDHL2, TMD8, MEC1, MEC2, 8E5, CCRF-CEM, MOLT-3, TALL-104, AML-193, THP-1, BDCM, HL-60, Jurkat, RPMI 8226, MOLT-4, RS4, K-562, KASUMI-1, Daudi, GA-10, Raji, JeKo-1, NK-92, and Mino. 
     In some embodiments, the sample for use in the methods is from any tissue or fluid from an individual. Samples include, but are not limited to, tissue (e.g. connective tissue, muscle tissue, nervous tissue, or epithelial tissue), whole blood, dissociated bone marrow, bone marrow aspirate, pleural fluid, peritoneal fluid, central spinal fluid, abdominal fluid, pancreatic fluid, cerebrospinal fluid, brain fluid, ascites, pericardial fluid, urine, saliva, bronchial lavage, sweat, tears, ear flow, sputum, hydrocele fluid, semen, vaginal flow, milk, amniotic fluid, and secretions of respiratory, intestinal or genitourinary tract. In some embodiments, the sample is a tissue sample, such as a sample obtained from a biopsy or a tumor tissue sample. In some embodiments, the sample is a blood serum sample. In some embodiments, the sample is a blood cell sample containing one or more peripheral blood mononuclear cells (PBMCs). In some embodiments, the sample contains one or more circulating tumor cells (CTCs). In some embodiments, the sample contains one or more disseminated tumor cells (DTC, e.g., in a bone marrow aspirate sample). 
     In some embodiments, the samples are obtained from the individual by any suitable means of obtaining the sample using well-known and routine clinical methods. Procedures for obtaining tissue samples from an individual are well known. For example, procedures for drawing and processing tissue sample such as from a needle aspiration biopsy is well-known and is employed to obtain a sample for use in the methods provided. Typically, for collection of such a tissue sample, a thin hollow needle is inserted into a mass such as a tumor mass for sampling of cells that, after being stained, will be examined under a microscope. 
     Sample Preparation and Analysis 
     In some embodiments, the sample is a sample solution. In some instances, the sample solution comprises a solution such as a buffer (e.g. phosphate buffered saline) or a media. In some embodiments, the media is an isotopically labeled media. In some instances, the sample solution is a cell solution. 
     In some embodiments, the sample (e.g., cells or a cell solution) is incubated with a cysteine-reactive probe for analysis of protein cysteine-reactive probe interactions. In some instances, the sample (e.g., cells or a cell solution) is further incubated in the presence of a small molecule fragment prior to addition of the cysteine-reactive probe. In some instances, the sample is compared with a control. In some instances, the control comprises the cysteine-reactive probe but not the small molecule fragment. In some instances, a difference is observed between a set of cysteine-reactive probe protein interactions between the sample and the control. In some instances, the difference correlates to the interaction between the small molecule fragment and the cysteine containing proteins. 
     In some embodiments, the sample (e.g. cells or a cell solution) is further labeled for analysis of cysteine-reactive probe protein interactions. In some instances, the sample (e.g. cells or a cell solution) is labeled with an enriched media. In some cases, the sample (e.g. cells or a cell solution) is labeled with isotope-labeled amino acids, such as  13 C or  15 N-labeled amino acids. In some cases, the labeled sample is further compared with a non-labeled sample to detect differences in cysteine-reactive probe protein interactions between the two samples. In some instances, this difference is a difference of a cysteine containing protein and its interaction with a small molecule fragment in the labeled sample versus the non-labeled sample. In some instances, the difference is an increase, decrease or a lack of protein cysteine-reactive probe interaction in the two samples. In some instances, the isotope-labeled method is termed SILAC, stable isotope labeling using amino acids in cell culture. 
     In some instances, the sample is divided into a first cell solution and a second cell solution. In some cases, the first cell solution is incubated with a small molecule fragment for an extended period of time prior to incubating the first cell solution with a first cysteine-reactive probe to generate a first group of cysteine-reactive probe-protein complexes. In some instances, the extended period of time is about 5, 10, 15, 20, 30, 60, 90, 120 minutes or longer. In some instances, the second cell solution comprises a second cysteine-reactive probe to generate a second group of cysteine-reactive probe-protein complexes. In some instances, the first cysteine-reactive probe and the second cysteine-reactive probe are the same. In some embodiments, cells from the second cell solution are further treated with a buffer, such as a control buffer, in which the buffer does not contain a small molecule fragment. In some embodiments, the control buffer comprises dimethyl sulfoxide (DMSO). 
     In some embodiments, the cysteine-reactive probe-protein complex is further conjugated to a chromophore, such as a fluorophore. In some instances, the cysteine-reactive probe-protein complex is separated and visualized utilizing an electrophoresis system, such as through a gel clectrophoresis, or a capillary electrophoresis. Exemplary gel electrophoresis includes agarose based gels, polyacrylamide based gels, or starch based gels. In some instances, the cysteine-reactive probe-protein is subjected to a native electrophoresis condition. In some instances, the cysteine-reactive probe-protein is subjected to a denaturing electrophoresis condition. 
     In some instances, the cysteine-reactive probe-protein after harvesting is further fragmentized to generate protein fragments. In some instances, fragmentation is generated through mechanical stress, pressure, or chemical means. In some instances, the protein from the cysteine-reactive probe-protein complexes is fragmented by a chemical means. In some embodiments, the chemical means is a protease. Exemplary proteases include, but are not limited to, serine proteases such as chymotrypsin A, penicillin G acylase precursor, dipeptidase E, DmpA aminopeptidase, subtilisin, prolyl oligopeptidase, D-Ala-D-Ala peptidase C, signal peptidase I, cytomegalovirus assemblin, Lon-A peptidase, peptidase Clp,  Escherichia coli  phage KIF endosialidase CIMCD self-cleaving protein, nucleoporin 145, lactoferrin, murein tetrapeptidase LD-carboxypeptidase, or rhomboid-1; threonine proteases such as omithine acetyltransferase; cysteine proteases such as TEV protease, amidophosphoribosyltransferase precursor, gamma-glutamyl hydrolase ( Rattus norvegicus ), hedgehog protein. DmpA aminopeptidase, papain, bromelain, cathepsin K, calpain, caspase-1, separase, adenain, pyroglutamyl-peptidase I, sortase A, hepatitis C virus peptidase 2, sindbis virus-type nsP2 peptidase, dipeptidyl-peptidase VI, or DeSI-1 peptidase; aspartate proteases such as beta-secretase 1 (BACE), beta-secretase 2 (BACE2), cathepsin D, cathepsin E, chymosin, napsin-A, nepenthesin, pepsin, plasmepsin, presenilin, or renin; glutamic acid proteases such as AfuGprA; and metalloproteases such as peptidase_M48. 
     In some instances, the fragmentation is a random fragmentation. In some instances, the fragmentation generates specific lengths of protein fragments, or the shearing occurs at particular sequence of amino acid regions. 
     In some instances, the protein fragments are further analyzed by a proteomic method such as by liquid chromatography (LC) (e.g. high performance liquid chromatography), liquid chromatography-mass spectrometry (LC-MS), matrix-assisted laser desorption/ionization (MALDI-TOF), gas chromatography-mass spectrometry (GC-MS), capillary electrophoresis-mass spectrometry (CE-MS), or nuclear magnetic resonance imaging (NMR). 
     In some embodiments, the LC method is any suitable LC methods well known in the art, for separation of a sample into its individual parts. This separation occurs based on the interaction of the sample with the mobile and stationary phases. Since there are many stationary/mobile phase combinations that are employed when separating a mixture, there are several different types of chromatography that are classified based on the physical states of those phases. In some embodiments, the LC is further classified as normal-phase chromatography, reverse-phase chromatography, size-exclusion chromatography, ion-exchange chromatography, affinity chromatography, displacement chromatography, partition chromatography, flash chromatography, chiral chromatography, and aqueous normal-phase chromatography. 
     In some embodiments, the LC method is a high performance liquid chromatography (HPLC) method. In some embodiments, the HPLC method is further categorized as normal-phase chromatography, reverse-phase chromatography, size-exclusion chromatography, ion-exchange chromatography, affinity chromatography, displacement chromatography, partition chromatography, chiral chromatography, and aqueous normal-phase chromatography. 
     In some embodiments, the HPLC method of the present disclosure is performed by any standard techniques well known in the art. Exemplary HPLC methods include hydrophilic interaction liquid chromatography (HILIC), electrostatic repulsion-hydrophilic interaction liquid chromatography (ERLIC) and reverse phase liquid chromatography (RPLC). 
     In some embodiments, the LC is coupled to a mass spectroscopy as a LC-MS method. In some embodiments, the LC-MS method includes ultra-performance liquid chromatography-electrospray ionization quadrupole time-of-flight mass spectrometry (UPLC-ESI-QTOF-MS), ultra-performance liquid chromatography-electrospray ionization tandem mass spectrometry (UPLC-ESI-MS/MS), reverse phase liquid chromatography-mass spectrometry (RPLC-MS), hydrophilic interaction liquid chromatography-mass spectrometry (HILIC-MS), hydrophilic interaction liquid chromatography-triple quadrupole tandem mass spectrometry (HILIC-QQQ), electrostatic repulsion-hydrophilic interaction liquid chromatography-mass spectrometry (ERLIC-MS), liquid chromatography time-of-flight mass spectrometry (LC-QTOF-MS), liquid chromatography-tandem mass spectrometry (LC-MS/MS), multidimensional liquid chromatography coupled with tandem mass spectrometry (LC/LC-MS/MS). In some instances, the LC-MS method is LC/LC-MS/MS. In some embodiments, the LC-MS methods of the present disclosure are performed by standard techniques well known in the art. 
     In some embodiments, the GC is coupled to a mass spectroscopy as a GC-MS method. In some embodiments, the GC-MS method includes two-dimensional gas chromatography time-of-flight mass spectrometry (GC*GC-TOFMS), gas chromatography time-of-flight mass spectrometry (GC-QTOF-MS) and gas chromatography-tandem mass spectrometry (GC-MS/MS). 
     In some embodiments, CE is coupled to a mass spectroscopy as a CE-MS method. In some embodiments, the CE-MS method includes capillary electrophoresis-negative electrospray ionization-mass spectrometry (CE-ESI-MS), capillary electrophoresis-negative electrospray ionization-quadrupole time of flight-mass spectrometry (CE-ESI-QTOF-MS) and capillary electrophoresis-quadrupole time of flight-mass spectrometry (CE-QTOF-MS). 
     In some embodiments, the nuclear magnetic resonance (NMR) method is any suitable method well known in the art for the detection of one or more cysteine binding proteins or protein fragments disclosed herein. In some embodiments, the NMR method includes one dimensional (ID) NMR methods, two dimensional (2D) NMR methods, solid state NMR methods and NMR chromatography. Exemplary ID NMR methods include  1 Hydrogen,  13 Carbon,  15 Nitrogen,  17 Oxygen,  19 Fluorine,  31 Phosphorus,  39 Potassium,  23 Sodium,  33 Sulfur,  87 Strontium,  27 Aluminium,  43 Calcium,  35 Chlorine,  37 Chlorine,  63 Copper,  65 Copper,  57 Iron,  25 Magnesium,  199 Mercury or  67 Zinc NMR method, distortionless enhancement by polarization transfer (DEPT) method, attached proton test (APT) method and ID-incredible natural abundance double quantum transition experiment (INADEQUATE) method. Exemplary 2D NMR methods include correlation spectroscopy (COSY), total correlation spectroscopy (TOCSY), 2D-INADEQUATE, 2D-adequate double quantum transfer experiment (ADEQUATE), nuclear overhauser effect spectroscopy (NOSEY), rotating-frame NOE spectroscopy (ROESY), heteronuclear multiple-quantum correlation spectroscopy (HMQC), heteronuclear single quantum coherence spectroscopy (HSQC), short range coupling and long range coupling methods. Exemplary solid state NMR method include solid state  13 Carbon NMR, high resolution magic angle spinning (HR-MAS) and cross polarization magic angle spinning (CP-MAS) NMR methods. Exemplary NMR techniques include diffusion ordered spectroscopy (DOSY), DOSY-TOCSY and DOSY-HSQC. 
     In some embodiments, the protein fragments are analyzed by method as described in Weerapana et al., “Quantitative reactivity profiling predicts functional cysteines in proteomes,”  Nature,  468:790-795 (2010). 
     In some embodiments, the results from the mass spectroscopy method are analyzed by an algorithm for protein identification. In some embodiments, the algorithm combines the results from the mass spectroscopy method with a protein sequence database for protein identification. In some embodiments, the algorithm comprises ProLuCID algorithm, Probity, Scaffold, SEQUEST, or Mascot. 
     In some embodiments, a value is assigned to each of the protein from the cystein-reactive probe-protein complex. In some embodiments, the value assigned to each of the protein from the cysteine-reactive probe-protein complex is obtained from the mass spectroscopy analysis. In some instances, the value is the area-under-the curve from a plot of signal intensity as a function of mass-to-charge ratio. In some embodiments, a first value is assigned to the protein obtained from the first cell solution and a second value is assigned to the same protein obtained from the second cell solution. In some instances, a ratio is calculated between the two values. In some instances, a ratio of greater than 2 indicates that the protein is a candidate for interacting with a drug or that the protein is a cysteine binding protein. In some instances, the ratio is greater than 2.5, 3, 3.5, 4, 4.5, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20. In some cases, the ratio is at most 20. 
     In some instances, the ratio is calculated based on averaged values. In some instances, the averaged value is an average of at least two, three, or four values of the protein from each cell solution, or that the protein is observed at least two, three, or four times in each cell solution and a value is assigned to each observed time. In some instances, the ratio further has a standard deviation of less than 12, 10, or 8. 
     In some instances, a value is not an averaged value. In some instances, the ratio is calculated based on value of a protein observed only once in a cell population. In some instances, the ratio is assigned with a value of 20. 
     In some embodiments, in the context of identifying a cysteine containing protein as a small fragment molecule binding target, a first ratio is obtained from two cell solutions in which both cell solutions have been incubated with a cysteine-reactive probe and the first cell solution is further incubated with a small molecule fragment. In some instances, the first ratio is further compared to a second ratio in which both cell solutions have been treated by cysteine-reactive probes in the absence of a small molecule fragment. In some instances, the first ratio is greater than 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20. In some instances, the second ratio is greater than 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20. In some instances, if the first ratio is greater than 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 and the second ratio is from about 0.5 to about 2, the two ratios indicate that a protein is a drug binding target. 
     In some embodiments, the value further enables calculating a percentage of inhibition of the cysteine-reactive probe to the cysteine containing protein. In some embodiments, the percentage of inhibition of greater than 50%, 60%, 70%, 80%, 90%, or at 100% indicates that the cysteine containing protein is a candidate for interacting with the small molecule fragment. 
     Kits/Article of Manufacture 
     Disclosed herein, in certain embodiments, are kits and articles of manufacture for use with one or more methods described herein. In some embodiments, described herein is a kit for identifying a cysteine containing protein as a small molecule fragment binding target. In some instances, also described herein is a kit for mapping binding sites on a cysteine containing protein. In some cases, described herein is a kit for identifying cysteine binding proteins. In some embodiments, also described herein is a kit for a high throughput screening of a small molecule fragment for interaction with a cysteine containing protein. 
     In some embodiments, such kit includes cysteine-reactive probes such as the cysteine-reactive probes described herein, test compounds such as small molecule fragments or libraries and/or controls, and reagents suitable for carrying out one or more of the methods described herein. In some instances, the kit further comprises samples, such as a cell sample, and suitable solutions such as buffers or media. In some embodiments, the kit further comprises recombinant proteins for use in one or more of the methods described herein. In some embodiments, additional components of the kit comprises a carrier, package, or container that is compartmentalized to receive one or more containers such as vials, tubes, and the like, each of the container(s) comprising one of the separate elements to be used in a method described herein. Suitable containers include, for example, bottles, vials, plates, syringes, and test tubes. In one embodiment, the containers are formed from a variety of materials such as glass or plastic. 
     The articles of manufacture provided herein contain packaging materials. Examples of pharmaceutical packaging materials include, but are not limited to, bottles, tubes, bags, containers, and any packaging material suitable for a selected formulation and intended mode of use. 
     For example, the container(s) include cysteine-reactive probes, test compounds, and one or more reagents for use in a method disclosed herein. Such kits optionally include an identifying description or label or instructions relating to its use in the methods described herein. 
     A kit typically includes labels listing contents and/or instructions for use, and package inserts with instructions for use. A set of instructions will also typically be included. 
     In one embodiment, a label is on or associated with the container. In one embodiment, a label is on a container when letters, numbers or other characters forming the label are attached, molded or etched into the container itself; a label is associated with a container when it is present within a receptacle or carrier that also holds the container, e.g., as a package insert. In one embodiment, a label is used to indicate that the contents are to be used for a specific therapeutic application. The label also indicates directions for use of the contents, such as in the methods described herein. 
     Services 
     In some embodiments, the methods provided herein also perform as a service. In some instances, a service provider obtain from the customer a plurality of small molecule fragment candidates for analysis with one or more of the cysteine-reactive probes for screening. In some embodiments, the service provider screens the small molecule fragment candidates using one or more of the methods described herein, and then provide the results to the customer. In some instances, the service provider provides the appropriate reagents to the customer for analysis utilizing one or more of the cysteine-reactive probes and one or more of the methods described herein. In some cases, the customer performs one or more of the methods described herein and then provide the results to the service provider for analysis. In some embodiments, the service provider then analyzes the results and provides the results to the costumer. In some cases, the customer further analyze the results by interacting with software installed locally (at the customer&#39;s location) or remotely (e.g., on a server reachable through a network). Exemplary customers include pharmaceutical companies, clinical laboratories, physicians, patients, and the like. In some instances, a customer is any suitable customer or party with a need or desire to use the methods, systems, compositions, and kits described herein. 
     Digital Processing Device 
     In some embodiments, the methods described herein include a digital processing device, or use of the same. In further embodiments, the digital processing device includes one or more hardware central processing units (CPU) that carry out the device&#39;s functions. In still further embodiments, the digital processing device further comprises an operating system configured to perform executable instructions. In some embodiments, the digital processing device is optionally connected to a computer network. In further embodiments, the digital processing device is optionally connected to the Internet such that it accesses the World Wide Web. In still further embodiments, the digital processing device is optionally connected to a cloud computing infrastructure. In other embodiments, the digital processing device is optionally connected to an intranet. In other embodiments, the digital processing device is optionally connected to a data storage device. 
     In accordance with the description herein, suitable digital processing devices include, by are not limited to, server computers, desktop computers, laptop computers, notebook computers, subnotebook computers, netbook computers, netpad computers, set-top computers, media streaming devices, handheld computers, Internet appliances, mobile smartphones, tablet computers, personal digital assistants, video game consoles, and vehicles. Suitable tablet computers include those with booklet, slate, or convertible configurations. 
     In some embodiments, the digital processing device includes an operating system configured to perform executable instructions. The operating system is, for example, software, including programs and data, which manages the device&#39;s hardware and provides services for execution of applications. Suitable server operating systems include, by way of non-limiting examples. FreeBSD, OpenBSD, NetBSD®, Linux, Apple® Mac OS X Server®, Oracle® Solaris®, Windows Server®, and Novell® NetWare®. Suitable personal computer operating systems include, by way of non-limiting examples, Microsoft® Windows®, Apple® Mac OS X®, UNIX®, and UNIX-like operating systems such as GNU/Linux®. In some embodiments, the operating system is provided by cloud computing. Suitable mobile smart phone operating systems include, by way of non-limiting examples, Nokia® Symbian® OS, Apple® iOS®, Research In Motion® BlackBerry OS®, Google® Android®, Microsoft® Windows Phone® OS, Microsoft® Windows Mobile® OS, Linux®, and Palm® WebOS®. Suitable media streaming device operating systems include, by way of non-limiting examples, Apple TV®, Roku®, Boxee®, Google TV®, Google Chromecast®, Amazon Fire®, and Samsung® HomeSync®. Suitable video game console operating systems include, by way of non-limiting examples, Sony® PS3®, Sony® PS4®, Microsoft® Xbox 360®, Microsoft Xbox One, Nintendo® Wii®, Nintendo® Wii U®, and Ouya®. 
     In some embodiments, the device includes a storage and/or memory device. The storage and/or memory device is one or more physical apparatuses used to store data or programs on a temporary or permanent basis. In some embodiments, the device is volatile memory and requires power to maintain stored information. In some embodiments, the device is non-volatile memory and retains stored information when the digital processing device is not powered. In further embodiments, the non-volatile memory comprises flash memory. In some embodiments, the non-volatile memory comprises dynamic random-access memory (DRAM). In some embodiments, the non-volatile memory comprises ferroelectric random access memory (FRAM). In some embodiments, the non-volatile memory comprises phase-change random access memory (PRAM). In other embodiments, the device is a storage device including, by way of non-limiting examples, CD-ROMs, DVDs, flash memory devices, magnetic disk drives, magnetic tapes drives, optical disk drives, and cloud computing based storage. In further embodiments, the storage and/or memory device is a combination of devices such as those disclosed herein. 
     In some embodiments, the digital processing device includes a display to send visual information to a user. In some embodiments, the display includes a cathode ray tube (CRT), a liquid crystal display (LCD), a thin film transistor liquid crystal display (TFT-LCD), an organic light emitting diode (OLED) display, a plasma display, a video projector, or a combination thereof. 
     In some embodiments, the digital processing device includes an input device to receive information from a user. In some embodiments, the input device is a keyboard. In some embodiments, the input device is a pointing device including, by way of non-limiting examples, a mouse, trackball, track pad, joystick, game controller, or stylus. In some embodiments, the input device is a touch screen or a multi-touch screen. In other embodiments, the input device is a microphone to capture voice or other sound input. In other embodiments, the input device is a video camera or other sensor to capture motion or visual input. In further embodiments, the input device is a Kinect™, Leap Motion™, or the like. In still further embodiments, the input device is a combination of devices such as those disclosed herein. 
     In some embodiments, the systems and methods disclosed herein include one or more non-transitory computer readable storage media encoded with a program including instructions executable by the operating system of an optionally networked digital processing device. In further embodiments, a computer readable storage medium is a tangible component of a digital processing device. In still further embodiments, a computer readable storage medium is optionally removable from a digital processing device. In some embodiments, a computer readable storage medium includes, by way of non-limiting examples, CD-ROMs, DVDs, flash memory devices, solid state memory, magnetic disk drives, magnetic tape drives, optical disk drives, cloud computing systems and services, and the like. In some cases, the program and instructions are permanently, substantially permanently, semi-permanently, or non-transitorily encoded on the media. 
     In some embodiments, the systems and methods disclosed herein include at least one computer program, or use of the same. A computer program includes a sequence of instructions, executable in the digital processing device&#39;s CPU, written to perform a specified task. In some embodiments, computer readable instructions are implemented as program modules, such as functions, objects, Application Programming Interfaces (APIs), data structures, and the like, that perform particular tasks or implement particular abstract data types. 
     In some embodiments, the functionality of the computer readable instructions are combined or distributed as desired in various environments. In some embodiments, a computer program comprises one sequence of instructions. In some embodiments, a computer program comprises a plurality of sequences of instructions. In some embodiments, a computer program is provided from one location. In other embodiments, a computer program is provided from a plurality of locations. In various embodiments, a computer program includes one or more software modules. In various embodiments, a computer program includes, in part or in whole, one or more web applications, one or more mobile applications, one or more standalone applications, one or more web browser plug-ins, extensions, add-ins, or add-ons, or combinations thereof. 
     In some embodiments, a computer program includes a web application. A web application, in various embodiments, utilizes one or more software frameworks and one or more database systems. In some embodiments, a web application is created upon a software framework such as Microsoft® .NET or Ruby on Rails (RoR). In some embodiments, a web application utilizes one or more database systems including, by way of non-limiting examples, relational, non-relational, object oriented, associative, and XML database systems. In further embodiments, suitable relational database systems include, by way of non-limiting examples, Microsoft® SQL Server, mySQL™, and Oracle®. A web application, in various embodiments, is written in one or more versions of one or more languages. In some embodiments, a web application is written in one or more markup languages, presentation definition languages, client-side scripting languages, server-side coding languages, database query languages, or combinations thereof. In some embodiments, a web application is written to some extent in a markup language such as Hypertext Markup Language (HTML). Extensible Hypertext Markup Language (XHTML), or eXtensible Markup Language (XML). In some embodiments, a web application is written to some extent in a presentation definition language such as Cascading Style Sheets (CSS). In some embodiments, a web application is written to some extent in a client-side scripting language such as Asynchronous Javascript and XML (AJAX), Flash® Actionscript, Javascript, or Silverlight®. In some embodiments, a web application is written to some extent in a server-side coding language such as Active Server Pages (ASP), ColdFusion®, Perl, Java™, JavaServer Pages (JSP), Hypertext Preprocessor (PHP), Python™, Ruby, Tel, Smalltalk, WebDNA®, or Groovy. In some embodiments, a web application is written to some extent in a database query language such as Structured Query Language (SQL). In some embodiments, a web application integrates enterprise server products such as IBM® Lotus Domino®. In some embodiments, a web application includes a media player element. In various further embodiments, a media player element utilizes one or more of many suitable multimedia technologies including, by way of non-limiting examples, Adobe® Flash®, HTML 5, Apple® QuickTime®, Microsoft® Silverlight®, Java™, and Unity®. 
     In some embodiments, a computer program includes a mobile application provided to a mobile digital processing device. In some embodiments, the mobile application is provided to a mobile digital processing device at the time it is manufactured. In other embodiments, the mobile application is provided to a mobile digital processing device via the computer network described herein. 
     In view of the disclosure provided herein, a mobile application is created by techniques using hardware, languages, and development environments. Suitable programming languages include, by way of non-limiting examples, C, C++, C #, Objective-C, Java™, Javascript, Pascal, Object Pascal, Python™, Ruby, VB.NET, WML, and XHTML/HTML with or without CSS, or combinations thereof. 
     Suitable mobile application development environments are available from several sources. Commercially available development environments include, by way of non-limiting examples, AirplaySDK, alcheMo, Appcelerator®, Celsius, Bedrock, Flash Lite, .NET Compact Framework, Rhomobile, and WorkLight Mobile Platform. Other development environments are available without cost including, by way of non-limiting examples, Lazarus, MobiFlex, MoSync, and Phonegap. Also, mobile device manufacturers distribute software developer kits including, by way of non-limiting examples, iPhone and iPad (iOS) SDK, Android™ SDK, BlackBerry® SDK, BREW SDK, Palm® OS SDK, Symbian SDK, webOS SDK, and Windows® Mobile SDK. 
     In some embodiments, commercial forums for distribution of mobile applications include, by way of non-limiting examples, Apple® App Store, Android™ Market, BlackBerry® App World, App Store for Palm devices, App Catalog for webOS, Windows® Marketplace for Mobile, Ovi Store for Nokia® devices, Samsung® Apps, and Nintendo® DSi Shop. 
     In some embodiments, a computer program includes a standalone application, which is a program that is run as an independent computer process, not an add-on to an existing process, e.g., not a plug-in. In some instances, standalone applications are compiled. A compiler is a computer program(s) that transforms source code written in a programming language into binary object code such as assembly language or machine code. Suitable compiled programming languages include, by way of non-limiting examples, C, C++, Objective-C, COBOL, Delphi, Eiffel, Java™, Lisp, Python™, Visual Basic, and VB .NET, or combinations thereof. Compilation is often performed, at least in part, to create an executable program. In some embodiments, a computer program includes one or more executable complied applications. 
     In some embodiments, the computer program includes a web browser plug-in. In computing, a plug-in is one or more software components that add specific functionality to a larger software application. Makers of software applications support plug-ins to enable third-party developers to create abilities which extend an application, to support easily adding new features, and to reduce the size of an application. When supported, plug-ins enable customizing the functionality of a software application. For example, plug-ins are commonly used in web browsers to play video, generate interactivity, scan for viruses, and display particular file types. In some instances, web browser plug-ins include Adobe® Flash® Player, Microsoft® Silverlight®, and Apple® QuickTime®. In some embodiments, the toolbar comprises one or more web browser extensions, add-ins, or add-ons. In some embodiments, the toolbar comprises one or more explorer bars, tool bands, or desk bands. 
     In view of the disclosure provided herein, plug-in frameworks are available that enable development of plug-ins in various programming languages, including, by way of non-limiting examples, C++, Delphi, Java™, PHP, Python™, and VB .NET, or combinations thereof. 
     Web browsers (also called Internet browsers) are software applications, designed for use with network-connected digital processing devices, for retrieving, presenting, and traversing information resources on the World Wide Web. Suitable web browsers include, by way of non-limiting examples, Microsoft® Internet Explorer, Mozilla® Firefox®, Google® Chrome, Apple® Safari®, Opera Software® Opera®, and KDE Konqueror. In some embodiments, the web browser is a mobile web browser. Mobile web browsers (also called mircrobrowsers, mini-browsers, and wireless browsers) are designed for use on mobile digital processing devices including, by way of non-limiting examples, handheld computers, tablet computers, netbook computers, subnotebook computers, smartphones, music players, personal digital assistants (PDAs), and handheld video game systems. Suitable mobile web browsers include, by way of non-limiting examples, Google® Android® browser, RIM Blackberry® Browser, Apple® Safari®, Palm® Blazer, Palm® WebOS® Browser, Mozilla® Firefox® for mobile, Microsoft® Internet Explorer® Mobile, Amazon® Kindle® Basic Web, Nokia® Browser, Opera Software® Opera® Mobile, and Sony® PSP™ browser. 
     In some embodiments, the systems and methods disclosed herein include software, server, and/or database modules, or use of the same. In view of the disclosure provided herein, software modules are created and implemented in a multitude of ways. In various embodiments, a software module comprises a file, a section of code, a programming object, a programming structure, or combinations thereof. In further various embodiments, a software module comprises a plurality of files, a plurality of sections of code, a plurality of programming objects, a plurality of programming structures, or combinations thereof. In various embodiments, the one or more software modules comprise, by way of non-limiting examples, a web application, a mobile application, and a standalone application. In some embodiments, software modules are in one computer program or application. In other embodiments, software modules are in more than one computer program or application. In some embodiments, software modules are hosted on one machine. In other embodiments, software modules are hosted on more than one machine. In further embodiments, software modules are hosted on cloud computing platforms. In some embodiments, software modules are hosted on one or more machines in one location. In other embodiments, software modules are hosted on one or more machines in more than one location. 
     In some embodiments, the methods and systems disclosed herein include one or more databases, or use of the same. In view of the disclosure provided herein, databases are suitable for storage and retrieval of analytical information described elsewhere herein. In various embodiments, suitable databases include, by way of non-limiting examples, relational databases, non-relational databases, object oriented databases, object databases, entity-relationship model databases, associative databases, and XML databases. In some embodiments, a database is internet-based. In further embodiments, a database is web-based. In still further embodiments, a database is cloud computing-based. In other embodiments, a database is based on one or more local computer storage devices. 
     Server 
     In some embodiments, the methods provided herein are processed on a server or a computer server ( FIG. 2 ). In some embodiments, the server  401  includes a central processing unit (CPU, also “processor”)  405  which is a single core processor, a multi core processor, or plurality of processors for parallel processing. In some embodiments, a processor used as part of a control assembly is a microprocessor. In some embodiments, the server  401  also includes memory  410  (e.g. random access memory, read-only memory, flash memory); electronic storage unit  415  (e.g. hard disk); communications interface  420  (e.g. network adaptor) for communicating with one or more other systems; and peripheral devices  425  which includes cache, other memory, data storage, and/or electronic display adaptors. The memory  410 , storage unit  415 , interface  420 , and peripheral devices  425  are in communication with the processor  405  through a communications bus (solid lines), such as a motherboard. In some embodiments, the storage unit  415  is a data storage unit for storing data. The server  401  is operatively coupled to a computer network (“network”)  430  with the aid of the communications interface  420 . In some embodiments, a processor with the aid of additional hardware is also operatively coupled to a network. In some embodiments, the network  430  is the Internet, an intranet and/or an extranet, an intranet and/or extranet that is in communication with the Internet, a telecommunication or data network. In some embodiments, the network  430  with the aid of the server  401 , implements a peer-to-peer network, which enables devices coupled to the server  401  to behave as a client or a server. In some embodiments, the server is capable of transmitting and receiving computer-readable instructions (e.g., device/system operation protocols or parameters) or data (e.g., sensor measurements, raw data obtained from detecting metabolites, analysis of raw data obtained from detecting metabolites, interpretation of raw data obtained from detecting metabolites, etc.) via electronic signals transported through the network  430 . Moreover, in some embodiments, a network is used, for example, to transmit or receive data across an international border. 
     In some embodiments, the server  401  is in communication with one or more output devices  435  such as a display or printer, and/or with one or more input devices  440  such as, for example, a keyboard, mouse, or joystick. In some embodiments, the display is a touch screen display, in which case it functions as both a display device and an input device. In some embodiments, different and/or additional input devices are present such an enunciator, a speaker, or a microphone. In some embodiments, the server uses any one of a variety of operating systems, such as for example, any one of several versions of Windows®, or of MacOS®, or of Unix®, or of Linux®. 
     In some embodiments, the storage unit  415  stores files or data associated with the operation of a device, systems or methods described herein. 
     In some embodiments, the server communicates with one or more remote computer systems through the network  430 . In some embodiments, the one or more remote computer systems include, for example, personal computers, laptops, tablets, telephones. Smart phones, or personal digital assistants. 
     In some embodiments, a control assembly includes a single server  401 . In other situations, the system includes multiple servers in communication with one another through an intranet, extranet and/or the Internet. 
     In some embodiments, the server  401  is adapted to store device operation parameters, protocols, methods described herein, and other information of potential relevance. In some embodiments, such information is stored on the storage unit  415  or the server  401  and such data is transmitted through a network. 
     Certain Terminology 
     Unless defined otherwise, all technical and scientific terms used herein have the same meaning as is commonly understood by one of skill in the art to which the claimed subject matter belongs. It is to be understood that the foregoing general description and the following detailed description are exemplary and explanatory only and are not restrictive of any subject matter claimed. In this application, the use of the singular includes the plural unless specifically stated otherwise. It must be noted that, as used in the specification and the appended claims, the singular forms “a,” “an” and “the” include plural referents unless the context clearly dictates otherwise. In this application, the use of “or” means “and/or” unless stated otherwise. Furthermore, use of the term “including” as well as other forms, such as “include”. “includes,” and “included,” is not limiting. 
     As used herein, ranges and amounts can be expressed as “about” a particular value or range. About also includes the exact amount. Hence “about 5 μL” means “about 5 μL” and also “5 μL.” Generally, the term “about” includes an amount that would be expected to be within experimental error. 
     The section headings used herein are for organizational purposes only and are not to be construed as limiting the subject matter described. 
     The term “protein”, as used herein, encompasses a full-length cysteine containing protein, a full-length functional cysteine containing protein, a cysteine containing protein fragment, or a functionally active cysteine containing protein fragment. In some instances, a protein described herein is also referred to as an “isolated protein”, or a protein that by virtue of its origin or source of derivation is not associated with naturally associated components that accompany it in its native state; is substantially free of other proteins from the same species; is expressed by a cell from a different species, or does not occur in nature. 
     The term “polypeptide”, as used herein, refers to any polymeric chain of amino acids. The term “polypeptide” encompasses native or modified cysteine containing protein, cysteine containing protein fragments, or polypeptide analogs comprising non-native amino acid residues. In some instances, a polypeptide is monomeric. In other instances, a polypeptide is polymeric. In some instances, a polypeptide described herein is also referred to as an “isolated polypeptide”, or a polypeptide that by virtue of its origin or source of derivation is not associated with naturally associated components that accompany it in its native state; is substantially free of other proteins from the same species; is expressed by a cell from a different species; or does not occur in nature. 
     As used herein, the terms “individual(s)”. “subject(s)” and “patient(s)” mean any mammal. In some embodiments, the mammal is a human. In some embodiments, the mammal is a non-human. None of the terms require or are limited to situations characterized by the supervision (e.g. constant or intermittent) of a health care worker (e.g. a doctor, a registered nurse, a nurse practitioner, a physician&#39;s assistant, an orderly or a hospice worker). 
     The term “alkyl” as used herein is a branched or unbranched saturated hydrocarbon group of 1 to 24 carbon atoms, such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, s-butyl, t-butyl, n-pentyl, isopentyl, s-pentyl, neopentyl, hexyl, heptyl, octyl, nonyl, decyl, dodecyl, tetradecyl, hexadecyl, eicosyl, tetracosyl, and the like. It is understood that the alkyl group is acyclic. In some instances, the alkyl group is branched or unbranched. In some instances, the alkyl group is also substituted or unsubstituted. For example, the alkyl group is substituted with one or more groups including, but not limited to, alkyl, cycloalkyl, alkoxy, amino, ether, halide, hydroxy, nitro, silyl, sulfo-oxo, or thiol. A “lower alkyl” group is an alkyl group containing from one to six (e.g., from one to four) carbon atoms. In some instances, the term alkyl group is also a C1 alkyl, C1-C2 alkyl, C1-C3 alkyl, C1-C4 alkyl, C1-05 alkyl, C1-C6 alkyl, C1-C7 alkyl, C1-C8 alkyl, C1-C9 alkyl, C1-C10 alkyl, and the like up to and including a C1-C24 alkyl. 
     The term “aryl” as used herein is a group that contains any carbon-based aromatic group including, but not limited to, benzene, naphthalene, phenyl, biphenyl, anthracene, and the like. The aryl group can be substituted or unsubstituted. In some instances, the aryl group is substituted with one or more groups including, but not limited to, alkyl, cycloalkyl, alkoxy, alkenyl, cycloalkenyl, alkynyl, cycloalkynyl, aryl, heteroaryl, aldehyde, —NH 2 , carboxylic acid, ester, ether, halide, hydroxy, ketone, azide, nitro, silyl, sulfo-oxo, or thiol. The term “biaryl” is a specific type of aryl group and is included in the definition of “aryl.” In addition, the aryl group is optionally a single ring structure or comprises multiple ring structures that are either fused ring structures or attached via one or more bridging groups such as a carbon-carbon bond. For example, biaryl refers to two aryl groups that are bound together via a fused ring structure, as in naphthalene, or are attached via one or more carbon-carbon bonds, as in biphenyl. 
     EXAMPLES 
     These examples are provided for illustrative purposes only and not to limit the scope of the claims provided herein. 
     Example 1 
     Biological Methods 
     Preparation of Human Cancer Cell Line Proteomes 
     All cell lines were obtained from ATCC, were used with a low passage number and were grown at 37° C. with 5% CO 2 . MDA-MB-231 cells and HEK-293T cells were grown in DMEM supplemented with 10% fetal bovine serum, penicillin, streptomycin and glutamine. Jurkat, Ramos and MUM2C cells were grown in RPMI-1640 medium supplemented with 10% fetal bovine serum, penicillin and streptomycin. For in vitro labeling, cells were grown to 100% confluence for MDA-MB-231 cells or until cell density reached 1.5 million cells/mL for Ramos and Jurkat cells. Cells were washed with cold PBS, scraped with cold PBS and cell pellets were isolated by centrifugation (1,400 g, 3 min, 4° C.), and stored at −80° C. until use. Cell pellets were lysed by sonication and fractionated (100,000 g, 45 min) to yield soluble and membrane fractions, which were then adjusted to a final protein concentration of 1.5 mg/mL for proteomics experiments and 1 mg/mL for gel-based ABPP experiments. The soluble lysate was prepared fresh from frozen pellets directly before each experiment. Protein concentration was determined using the Bio-Rad DC™ protein assay kit. 
     Screening of Fragment Electrophile Library by Gel-Based ABPP with IA-Rhodamine and Ac-Rho-DEVD-AMK (“DEVD” Disclosed as SEQ ID NO: 857) 
     25 μL of soluble proteome (1 mg/mL) was treated with fragment electrophiles (1 μL of 25×stock solution in DMSO) at ambient temperature for 1 h. IA-rhodamine (1 μL of 25 μM, final concentration=1 μM) was then added and allowed to react for an additional 1 h. The reactions were quenched with 8 μL of 4×SDS-PAGE loading buffer and the quenched samples analyzed by SDS-PAGE (10% polyacrylamide; 15 μL of sample/lane) and visualized by in-gel fluorescence using a flatbed fluorescent scanner (BioRad ChemiDoc™ MP or Hitachi FMBio IIe). To measure labeling of recombinant proteins expressed in  E. coli , purified protein was added to soluble proteome to a final concentration of 1 μM (CASP8, PRMT1, IMPDH2), 2 μM (TIGAR, IDH1) or 4 μM (IDH1 R132H) and the proteomes were treated as detailed above. IDH1 labeling by IA-rhodamine is relatively better in MDA-MB-231 soluble proteome when compared with Ramos and Jurkat soluble proteome. Recombinant, active CASP8 in soluble proteome was labeled with Rho-DEVD-AOMK (“DEVD” disclosed as SEQ ID NO: 857) (1 μL of 50 μM, final concentration=2 μM), quenched and analyzed by SDS-PAGE on 14% polyacrylamide gels. 
     Gel-Based ABPP with Alkyne-Containing Click Probes 
     25 μL of soluble proteome (1 mg/mL) was labeled with the indicated concentration of 18 or 19 (1 μL of 25× stock solution in DMSO) for 1 h at ambient temperature followed by copper-mediated azide-alkyne cycloaddition (CuAAC) conjugation to rhodamine-azide. CuAAC was performed with 20 μM rhodamine-azide (50× stock in DMSO), 1 mM tris(2-carboxyethyl)phosphine hydrochloride (TCEP; fresh 50× stock in water, final concentration=1 mM), ligand (17× stock in DMSO:t-butanol 1:4, final concentration=100 μM) and 1 mM CuSO 4  (50× stock in water, final concentration=1 mM). Samples were allowed to react for 1 h at ambient temperature before quenching with 8 μL 4×SDS-PAGE loading buffer. Quenched reactions were analyzed by SDS-PAGE and visualized by in-gel fluorescence. For CASP8 and IMPDH2 25 μL of soluble proteomes containing IMPDH2 or Pro-CASP8 (1 μM each respectively) were treated with the indicated fragment for 1 h prior to incubation for 1 h with 18 (1 μl, of 625 μM, final concentration=25 μM) for IMPDH2 or 61 (1 μl, of 625 μM, final concentration=25 μM) for CASP8. For MLTK, HEK 293T cells stably overexpressing MTLK 2  were treated with the indicated fragment electrophiles for 1 h, followed by labeling with 59 (1 μl, of 125 μM, final concentration=5 μM) for 1 h. These were followed by CuAAC conjugation to rhodamine-azide and evaluation by SDS-PAGE as described above. 
     Determination of In Vitro IC 50  Values 
     25 μL of proteomes containing the indicated protein were treated with fragment electrophiles for 1 h at ambient temperature, labeled with the probes detailed above for 1 h, quenched, and analyzed by SDS-PAGE and in-gel fluorescence visualization (n=3). IA-rhodamine was used as the probe for C161S-TIGAR, C409S-CASP8 and PRMT1, 59 was used as a probe for MLTK. The soluble proteome containing IMPDH2 was treated with ATP for 15 min prior to incubation with 18 (1 μl, of 625 μM, final concentration=25 μM) for 1 h. MLTK and IMPDH2 were subjected to CuAAC conjugation to rhodamine-azide as detailed above. The percentage of labeling was determined by quantifying the integrated optical intensity of the bands, using ImageJ software. Nonlinear regression analysis was used to determine the IC50 values from a dose-response curve generated using GraphPad Prism  6 . 
     IsoTOP-A BPP Sample Preparation 
     For in situ labeling, MDA-MB-231 cells were grown to 95% confluence and Ramos cells were grown to 1 million cells/mL. The media in all samples was replaced with fresh media, containing 200 μM of the indicated fragments and the cells were incubated at 37° C. for 2 h, washed with cold PBS, scraped into cold PBS and harvested by centrifugation (see prior section on “Preparation of human cancer cell line proteomes”). 
     Fragments 2, 3, 8, 9, 10, 12, 13, 14, 21, 27, 28, 29, 31, 33, 38, 45, 51 and 56 were screened at 200 μM in situ. Fragments 4 and 11 were screened at 100 μM in situ. Fragments 2, 3, 8, and 20 were tested at 50 μM in situ. 
     After in vitro or in situ fragment treatment, the samples were labeled for 1 h at ambient temperature with 100 μM iodoacetamide alkyne (IA-alkyne, 5 μL of 10 mM stock in DMSO). For direct labeling with 61, 61 (5 μL of 1 or 10 mM stocks in DMSO, final concentration=10 or 100 μM) was substituted for IA-alkyne. Samples were conjugated by CuAAC to either the light (fragment treated) or heavy (DMSO treated) TEV tags (10 μL of 5 mM stocks in DMSO, final concentration=100 μM), TCEP, TBTA ligand and CuSO 4  as detailed above. The samples were allowed to react for 1 h at which point the samples were centrifuged (16,000 g, 5 min, 4° C.). The resulting pellets were sonicated in ice-cold methanol (500 μL) and the resuspended light- and heavy-labeled samples were then combined and centrifuged (16,000 g, 5 min, 4° C.). The pellets were solubilized in PBS containing 1.2% SDS (1 mL) with sonication and heating (5 min, 95° C.) and any insoluble material was removed by an additional centrifugation step at ambient temperature (14,000 g, 1 min). 
     For each sample, 100 μL of streptavidin-agarose beads slurry (Pierce) was washed in 10 mL PBS and then resuspended in 5 mL PBS. The SDS-solubilized proteins were added to the suspension of streptavidin-agarose beads and the bead mixture was rotated for 3 h at ambient temperature. After incubation, the beads were pelleted by centrifugation (1.400 g, 3 min) and were washed (2×10 mL PBS and 2×10 mL water). 
     The beads were transferred to eppendorf tubes with 1 mL PBS, centrifuged (1,400 g, 3 min), and resuspended in PBS containing 6 M urea (500 μL). To this was added 10 mM DTT (25 μL of a 200 mM stock in water) and the beads were incubated at 65° C. for 15 mins, 20 mM iodoacetamide (25 μL of a 400 mM stock in water) was then added and allowed to react at 37° C. for 30 mins with shaking. The bead mixture was diluted with 900 μL PBS, pelleted by centrifugation (1,400 g, 3 min), and resuspended in 200 μL PBS. To this was added 1 mM CaCl 2  (2 μL of a 200 mM stock in water) and trypsin (2 μg, Promega, sequencing grade) and the digestion was allowed to proceed overnight at 37° C. with shaking. The beads were separated from the digest with Micro Bio-Spin columns (Bio-Rad) by centrifugation (1,000 g, 1 min), washed (2×1 mL PBS and 2×1 mL water) and then transferred to fresh eppendorfs with 1 mL water. The washed beads were washed once further in 140 μL TEV buffer (50 mM Tris, pH 8, 0.5 mM EDTA, 1 mM DTT) and then resuspended in 140 μL TEV buffer, 5 μL TEV protease (80 μM) was added and the reactions were rotated overnight at 29° C. The TEV digest was separated from the beads with Micro Bio-Spin columns by centrifugation (1,400 g, 3 min) and the beads were washed once with water (100 μL). The samples were then acidified to a final concentration of 5% (v/v) formic acid and stored at −80° C. prior to analysis. 
     Liquid-Chromatography-Mass-Spectrometry (LC-MS) Analysis of isoTOP-ABPP Samples 
     TEV digests were pressure loaded onto a 250 μm (inner diameter) fused silica capillary column packed with C18 resin (Aqua 5 μm, Phenomenex). The samples were analyzed by multidimensional liquid chromatography tandem mass spectrometry (MudPIT), using an LTQ-Velos Orbitrap mass spectrometer (Thermo Scientific) coupled to an Agilent 1200-series quaternary pump. The peptides were eluted onto a biphasic column with a 5 μm tip (100 μm fused silica, packed with C18 (10 cm) and bulk strong cation exchange resin (3 cm, SCX, Phenomenex,)) in a 5-step MudPIT experiment, using 0%, 30%, 60%, 90%, and 100% salt bumps of 500 mM aqueous ammonium acetate and using a gradient of 5-100% buffer B in buffer A (buffer A: 95% water, 5% acetonitrile, 0.1% formic acid; buffer B: 5% water, 95% acetonitrile, 0.1% formic acid) as has been described in Weerapana et al. Nat Protoc 2:1414-1425 (2007). Data was collected in data-dependent acquisition mode with dynamic exclusion enabled (20 s, repeat of 2). One full MS (MS1) scan (400-1800 m/z) was followed by 30 MS2 scans (ITMS) of the nth most abundant ions. 
     Peptide and Protein Identification 
     The MS2 spectra data were extracted from the raw file using RAW Xtractor (version 1.9.9.2; available at http://fields.scripps.edu/downloads.php). MS2 spectra data were searched using the ProLuCID algorithm (publicly available at http://fields.scripps.edu/downloads.php) using a reverse concatenated, nonredundant variant of the Human UniProt database (release-2012_11). Cysteine residues were searched with a static modification for carboxyamidomethylation (+57.02146) and up to one differential modification for either the light or heavy TEV tags (+464.28595 or +470.29976 respectively). Peptides were required to have at least one tryptic terminus and to contain the TEV modification. ProLuCID data was filtered through DTASelect (version 2.0) to achieve a peptide false-positive rate below 1%. 
     R Value Calculation and Processing 
     The ratios of heavy/light for each unique peptide (DMSO/compound treated; isoTOP-ABPP ratios, R values) were quantified with in-house CIMAGE software, using default parameters (3 ms 1 s per peak and signal to noise threshold 2.5). Site-specific engagement of electrophilic fragments was assessed by blockade of IA-alkyne probe labeling. For peptides that showed a ≥95% reduction in MS1 peak area from the fragment treated proteome (light TEV tag) when compared to the DMSO treated proteome (heavy TEV tag), a maximal ratio of 20 was assigned. Ratios for unique peptide entries were calculated for each experiment; overlapping peptides with the same modified cysteine (e.g. different charge states, MudPIT chromatographic steps or tryptic termini) were grouped together and the median ratio was reported as the final ratio (R). The peptide ratios reported by CIMAGE were further filtered to ensure the removal or correction of low quality ratios in each individual dataset. The quality filters applied were the following: removal of half tryptic peptides; for ratios with high standard deviations from the median (90% of the median or above) the lowest ratio was taken instead of the median; removal of peptides with R=20 and only a single ms2 event triggered during the elution of the parent ion; manual annotation of all the peptides with ratios of 20, removing any peptides with low-quality elution profiles that remained after the previous curation steps. Proteome reactivity values for individual fragments were computed as the percentage of the total quantified cysteine-containing peptides with R values≥4 (defined as liganded cysteines) for each replicate experiment and the final proteome reactivity value was calculated as the mean for all replicate experiments for each fragment from both MDA-MB-231 and Ramos cellular proteomes. 
     Cross-Data Processing 
     Biological replicates of the same compound and cell-line were averaged if the standard deviation was below 60% of the mean; otherwise the lowest value of the ratio set was taken. For peptides with multiple modified cysteines, the cysteine with the highest number of quantification events was kept and the remaining, redundant peptides were discarded. Peptides included in the aggregate dataset (those used for further bioinformatics and statistical analyses) were required to have been quantified in 3 experiments. Cysteines were categorized as liganded if they had at least two ratios R≥4 (hit fragments) and one ratio between 0.5 and 2 (control fragments). Although the majority (&gt;75% of fragments) were profiled in at least two biological replicates, some data from single replicate MS experiments were included. Averaged filtered data for all fragments and representative individual filtered datasets are found in Tables 1-3. 
     In Situ Data Processing 
     R values were calculated and individual datasets were filtered as described above (R value calculation and processing). Two categories of hits in situ were defined: 1) cysteines liganded in situ that were also observed as hits in vitro and 2) cysteines that detected in vitro, but were only liganded in situ. For the first category. R values for the same cysteine containing peptide from in vitro and in situ experiments were compared and if both had ratios R≥4, the cysteine was considered ligandable in situ. To qualify for the second category, two ratios R≥4 for replicates of two different fragments were required to be detected in situ and at least one of these fragments must be quantified as a non-hit with R≤2 in vitro. Additionally, another cysteine from the same protein was required to be unliganded in situ (R≤2) by the same fragment to control for the possibility that changes in R values from changes in protein expression upon fragment treatment rather than from fragment competition. 
     Functional Annotation of Liganded Cysteines 
     Custom python scripts were used to compile functional annotations available in the UniProtKB/Swiss-Prot Protein Knowledge database (release-2012_11). Relevant Uniprot entries were mined for available functional annotations at the residue level, specifically for annotations regarding enzyme catalytic residues (active sites), disulfides (redox active and structural) and metal binding sites. Liganded proteins were queried against the Drugbank database (Version 4.2) and fractionated into DrugBank and non-Drugbank proteins. Functional keywords assigned at the protein level were collected from the Uniprot database and the Drugbank and non-drugbank categories were further classified into protein functional classes. Cysteine reactivity data was re-processed using ProLuCID as detailed above (Peptide and protein identification). Cysteines found in both the reactivity and ligandability datasets were sorted based on their reactivity values (lower ratio indicates higher reactivity). The moving average of the percentage of total liganded cysteines within each reactivity bin (step-size 50) was taken. Custom python scripts were developed to collect relevant NMR and X-ray structures from the RCSB Protein Data Bank (PDB). For proteins without available PDB structures, sequence alignments, performed with BLAST to proteins deposited in the PDB, were used to identify structural homologues. For annotation of active-site and non-active cysteines, enzymes with structures in the PDB were manually inspected to evaluate the location of the cysteine. Cysteines were considered to reside in enzyme active sites if they were within 10 Å of active-site ligand or residue(s). Cysteines outside of the 10 Å range were deemed non-active-site residues. Histograms of fragment hit-rates across high-coverage, ligandable cysteines, active-site and non-active site cysteines were calculated from the subset of ligandable cysteines quantified in 10 or more separate experiments. The fragment hit rate is reported as the percentage of the total quantification events with R≥4. For analyses of trends within the whole data, including histograms and heatmaps, a cell-line merged dataset was used where data from the MDA-MB-231 experiments was taken first and the Ramos data was used if there was no data from MDA-MB-231 experiments for a particular fragment and cysteine. Heatmaps were generated in R (version 3.1.3) using the heatmap.2 algorithm. Protein structures were rendered using Pymol. 
     GSH Reactivity 
     Glutathione (GSH) was diluted to a final concentration of 125 μM in assay buffer (100 mM Tris, pH 8.8, 10% ethanol as co solvent). In triplicate, to 100 μL of the GSH mixture in a clear 96 well plate (Costar® Corning®), the indicated electrophile (2 μL of a 50 mM stock solution in DMSO, final concentration=500 μM) was added and the reaction mixture was incubated at room temperature for 1 h. 5 μL of Ellman&#39;s reagent (100 mM stock in IM NaOH, final concentration=5 mM) was added and the absorbance was measure at 440 nm on a plate reader (Tecan Infinite F500). The concentration of GSH remaining was calculated from a standard curve. 
     Reactive Cysteine Docking 
     In silico fragment library containing all chloroacetamide and acrylamide fragments from  FIG. 3  was prepared using Open Babel library with custom Python scripts. Fragments were modeled in their reactive form (i.e., with explicit chloroacetamide and acrylamide warheads). 3D coordinates were generated from SMILES strings, calculating their protonation state at pH 7.4, and then minimizing them using MMF94s forcefield (50K iterations steepest descent; 90K conjugate gradient); for chiral molecules with undefined configuration, all enantiomers were generated, resulting in 53 total fragments 
     For each protein, the UniProtKB ID was used to filter the PDB. Structures determined by X-ray crystallography were selected, privileging higher sequence coverage and structure resolution (See Table 5 for selected PDB IDs). When no human structures were available, the closest homologous organism available was selected (e.g. PRMT1 : R. norvegicus ). Protein structures were prepared following the standard AutoDock protocol. Waters, salts, and crystallographic additives were removed; AutoDockTools was used to add hydrogens, calculate Gasteiger-Marsili charges and generate PDBQT files. 
     MSMS reduced surface method was used to identify accessible cysteines. The protein volume was scanned using a probe radius of 1.5 Å; residues were considered accessible if they had at least one atom in contact with either external surfaces or internal cavities. 
     The fragment library was docked independently on each accessible cysteine using AutoDock 4.2. A grid box of 24.4×24.4×24.4 Å was centered on the geometric center of the residue; thiol hydrogen was removed from the side-chain, which was modeled as flexible during the docking; the rest of the structure was kept rigid. A custom 13-7 interaction potential was defined between the nucleophile sulfur and the reactive carbon in the ligands. The equilibrium distance (r eq ) was set to the length of the C-S covalent bond (1.8 Å); the potential well depth (ε eq ) varied between 1.0 and 0.175 to model to the reactivity of the different ligands. For each fragment, potential well depth was determined by dividing its proteomic reactivity percentage by 20, and the value for iodoacetamide was approximated as the maximum (2.5) for reference. The potential was implemented by modifying the force field table of AutoDock. Fragments were docked with no constraints, generating 100 poses using the default GA settings. For each fragment, the best docking score pose was analyzed: if the distance between the nucleophilic sulfur and the reactive carbon was ≤2.0 Å, the cysteine was considered covalently modified. If a residue was alkylated by at least one ligand, it was considered labeled. The docking score (i.e., negative binding energy) was calculated based on the estimated interaction energy of each fragment in its docked pose. The docking score of the best alkylating fragment defined the labeling score. The residue with the best labeling score was considered the most probable to be labeled. 
     Structural Modeling 
     IMPDH2 structure, including the Bateman domain, was modeled using I-TASSER. 
     Subcloning and Mutagenesis 
     Full length cDNAs encoding for IDH1 (Open Biosystems, Clone ID: 3880331) and IMPDH2 (Open Biosystems, Clone ID: 3447994) were subcloned into pET22b (+) (Novagen) with C-terminal His 6 -affinity tag (SEQ ID NO: 861). Full length cDNA encoding for TIGAR (Origene, Sc320794) was subcloned into pET28a (+) (Novagen) with N-terminal His-affinity tag (SEQ ID NO: 861). Full length PRMT1 subcloned into pET45b (+) (Novagen) was previously generated by the Cravatt lab. Full-length human CASP3 (residues 1-277) and a truncated CASP8 (residues 217-479) without the CARD domain was subcloned into pET23b (Novagen) with C-terminal His 6 -affinity tags (SEQ ID NO: 861). Cysteine mutants were generated using QuikChange site-directed mutagenesis, using primers containing the desired mutations and their respective compliments. 
     Recombinant Overexpression of TIGAR, IDH1, PRMT1 and IMPDH2 
     TIGAR, IDH1, PRMT1 and IMPDH2 were expressed in BL21(DE3) Chemically Competent Cells (NEB), grown on Terrific Broth supplemented with the desired antibiotic (50 μg/mL Kanamycin or 50 μg/mL Carbenicillin) to OD 600  of 0.8 and induced with 0.5 mM IPTG for 16 h at 18° C. Cells were immediately harvested and resuspended in 30 mL cold buffer A (25 mM Tris, pH 7.4, 200 mM NaCl, 10% glycerol, 1 mM BME), supplemented with lysozyme (Sigma), DNAase (NEB) and cOmplete protease inhibitor tablets (Roche), sonicated, and centrifuged (45,000 g, 30 min, 4° C.). The soluble fractions were collected and rotated for 1 h with 1 mL Ni-NTA slurry (Qiagen) at 4° C. The slurry was then transferred to a 50 mL volume, fritted column and collected by gravity flow. The resin was then washed with 100 mL buffer A containing 20 mM imidazole and eluted with 10 mL buffer A containing 200 mM imidazole. The eluant was concentrated to 2.5 mL (Amicon-Ultra-15, 10 kDa MW cutoff), buffer exchanged using PD10 columns (GE Amersham) into the storage buffer (50 mM HEPES, pH 7.4, 150 mM NaCl, 10% glycerol, 1 mM BME) and further concentrated (Amicon-Ultra-4, 10 kDa MW cutoff) to a final concentration of approximately 100 μM protein. Protein concentration was determined using the Bio-Rad DC™ protein assay kit. Protein purity was assayed by SDS-PAGE under reducing conditions and were &gt;95% pure. 
     Recombinant CASP3, CASP8 and TEV Protease Expression 
     CASP3, CASP8, pro-CASP8 (D374A, D384A) and an N-terminal MBP fusion-His 6 -TEV-Arg 6  protease construct pRK793 (“His 6 ” disclosed as SEQ ID NO: 861 and “Arg 6 ” disclosed as SEQ ID NO: 862) were expressed in  E. coli  BL21(DE3)pLysS cells (Stratagene). Cells were grown in 2×YT medium supplemented with 200 μg/ml ampicillin and 50 μg/ml chloramphenicol at 37° C. to an OD 600  of 0.8-1.0. Overexpression of caspase was induced with 0.2 mM IPTG at 30° C. for 4 h (CASP3) or at 12° C. overnight (CASP8) or with 0.5 mM IPTG at 30° C. for 4 h (TEV protease). Cells were immediately harvested and resuspended in ice cold buffer A (caspases: 100 mM Tris, pH 8.0, 100 mM NaCl; TEV protease: PBS) and subjected to 3 cycles of lysis by microfluidization (Microfluidics). The cell lysate was clarified by centrifugation (45,000 g, 30 min, 4° C.) and soluble fractions were loaded onto a 1 mL HisTrap HP Ni-NTA affinity column (GE Amersham) pre-equilibrated with buffer A and eluted with buffer A containing 200 mM imidazole. The eluted protein was immediately diluted two-fold with buffer B (20 mM Tris, pH 8.0) and purified by anion-exchange chromatography (HiTrap Q HP, GE Amersham) with a 30-column volume gradient to 50% of buffer B containing 1 M NaCl. The caspases were injected over a Superdex 200 16/60 gel filtration column (GE Amersham) and TEV protease over a Superdex 75 gel filtration column (GE Amersham) in buffer C (caspases: 20 mM Tris, pH 8.0, 50 mM NaCl; TEV protease: PBS, 10 mM DTT) to buffer exchange and to remove any remaining contaminants. Fractions containing the desired protein were pooled and concentrated to approximately 1 mg/mL (Millipore Ultrafree-15, 10 kDa MW cutoff). The purified proteins were immediately frozen and stored at −80° C. Protein concentrations were measured using both Bio-Rad colorimetric assay and A 280  absorbance in denaturing conditions. Protein purity was assayed by SDS-PAGE under reducing conditions and were &gt;98% pure. 
     Retroviral Overexpression of Flag-Tagged IDH1 Proteins 
     R132H-IDH1, including an additional K345K silent mutation to remove an unwanted restriction site and GFP were subcloned into a modified pCLNCX retroviral vector. Retrovirus was prepared by taking 1.5 μg of each pCLNCX vector and 1.5 μg pCMV-VSV-G and 20 μL of Roche X-tremeGeneHP DNA transfection reagent to transfect HEK-293RTV cells. The medium was replaced after 1 day of transfection and the following day the culture supernatant was collected and filtered through 0.5 μM filter, 10 mL of the filtrate, containing the desired virus, was used to infect MUM2C cells in the presence of polybrene (8 μg/mL) for 48 h, at which point the infected cells were selected for in medium containing 100 μg/mL hygromycin for 7-10 days. Surviving cells were expanded and cultured in complete RPMI-1640 medium containing hygromycin. 
     IDH1 NADP Assay 
     Recombinant IDH1 and C269S-IDH1 (100 μM in storage buffer) were diluted 1:200 in MDA-MB-231 cellular proteome (1 mg/mL). To 25 μL of this mixture was added 1 μL of the indicated compound (25× stock solution in DMSO) and the lysates were incubated for 1 h at room temperature in clear 96 well plates (Corning®, Costar®), 75 μL per well of a stock solution of NADP (13.3 mM) and isocitrate (13.3 mM) in IDH1 buffer (40 mM Tris, pH 7.4, 2 mM MgCl 2 , 0.01% pluronic) was added immediately before measuring UV absorbance at 340 nm on a 96 well UV absorbance plate reader (TECAN). Absorbance was measured for 45 minutes and the relative activities were calculated from the change in absorbance for the linear portion of the curve. 
     IDH1 2-Hydroxyglutarate (2-HG) Formation Assay 
     MUM2C cells stably overexpressing IDH1 R132H were seeded 1.5×10 6  cells/150 mm dish. The following day the indicated compounds (50 mM stock solutions in DMSO) or DMSO were added to the cells to the final concentrations indicated and were allowed to incubate for 2 h. Control cells overexpressing GFP were treated in parallel. The cells were washed in ice-cold PBS and collected by scraping in ice-cold PBS and centrifugation (1,400 g, 3 min, 4° C.). The cell pellets were then resuspended in 100 μL ice-cold PBS followed by sonication and centrifugation at 16,000 g for 10 min. Lysates were then buffer exchanged into IDH1 buffer (40 mM Tris, pH 7.4, 2 mM MgCl 2 ) with 0.5 mL ZEBA spin desalting columns (Thermo Fisher, 89882). The protein concentrations were adjusted to 3.5 mg/mL and 25 μL of the lysate was mixed with 25 μL of the reaction mixture (2.5 mM NADPH and 2.5 mM α-ketoglutarate in IDH1 buffer) and the reaction was allowed to proceed for 4 h at which point the reaction mixtures were quenched with 50 μL cold methanol, followed by a centrifugation (16,000 g, 10 min, 4° C.). Formation of 2-HG was followed by targeted LC/MS analysis. The reaction mixture was separated with a Luna-NH 2  column (5 μm, 100 Å, 50×4.6 mm, Phenomenex) with a precolumn (NH 2 , 4×3.0 mm) using a gradient of mobile phases A and B (mobile phase A: 100% CH 3 CN, 0.1% formic acid; mobile phase B: 95:5 (v/v) H 2 O:CH 3 CN, 50 mM NH 4 OAc, 0.2% NH 4 OH). The flow rate started at 0.1 mL/min. and the gradient consisted of 5 min 0% B, a linear increase to 100% B over 20 min at a flow rate of 0.4 mL/min, followed by an isocratic gradient of 100% B for 2 min at 0.5 mL/min before equilibrating for 3 min at 0% B at 0.4 mL/min (30 min total). For each run, the injection volume was 25 μL. MS analysis was performed on an Agilent G6410B tandem mass spectrometer with ESI source. The dwell time for 2-HG was set to 100 ms, and collision energy for 2-HG was set to 5. The capillary was set to 4 kV, and the fragmentor was set to 100 V. The drying gas temperature was 350° C., the drying gas flow rate was 11 L/min and the nebulizer pressure was 35 psi. The mass spectrometer was run in MRM mode, monitoring the transition of m/z from 146.7 to 129 for 2-HG (negative ionization mode). Treatments were conducted in triplicate. Background 2-HG production, calculated from the ‘mock’ GFP over expressing cells, was subtracted from the total 2-HG production. TIGAR activity assay 
     TIGAR activity assay was conducted as described in Gerin et al.  The Biochemical Journal  458:439-448 (2014). Formation of 3PG (3-phosphoglycerate) production from 23BPG (2,3-bisphosphoglycerate) was measured spectrophotometrically on a TECAN plate reader, measuring decrease in absorbance at 340 nm in clear, flat-bottom 96 well microplate (Corning® Costar®). 2 μL of recombinant TIGAR (10 mg/mL) was diluted into 1 mL dilution buffer (25 mM HEPES, pH 7.1, 25 mM KCl, 1 mM MgCl 2 ). 25 μL of diluted protein was incubated for 1 h with the indicated concentration of compound (1 μL, 25× stock in DMSO). Then 75 μL of assay mixture comprised of 25 mM HEPES (pH 7.1), 25 mM KCl, 1 mM MgCl 2 , 0.5 mM NADH, 1 mM DTT, 1 mM 23BPG, 1 mM ATP-Mg, the equivalent of 1 μL each of rabbit muscle GAPDH (4000 units/mL, Sigma, G5537) and yeast PG kinase (6300 units/mL, Sigma, P7634) was added to the protein and decrease in absorbance was monitored at 340 nm. The background, calculated from samples lacking TIGAR, was subtracted from samples containing TIGAR. Experiments were performed in quadruplicate. 
     PRMT1 In Vitro Methylation Assays 
     PRMT1 assays were conducted as described in Weerapana et al. Nature 468:790-795 (2010). Recombinant human PRMT1 (0.85 μM, wild type or C101S mutant) in 25 μL methylation buffer (20 mM This, pH 8.0, 200 mM NaCl, 0.4 mM EDTA) was pre-incubated with indicated fragments for 1 h and methylation activity was monitored after addition of 1 mg of recombinant histone 4 (NEB, M2504S) and  3 H-SAM (2 μCi). Reactions were further incubated for 60 min at ambient temperature and stopped with 4×SDS sample buffer. SDS-PAGE gels were fixed with 10% acetic acid/10% methanol (v/v), washed, and incubated with Amplify reagent (Amersham) before exposing to film at −80° C. for 3 days. 
     MLTK In Vitro Kinase Activity Assay 
     The kinase activity assay protocol was conducted as described in Wang et al. ACS Chemical biology 9:2194-2198 (2014). Kinase assay buffers, myelin basic protein (MBP) substrate and ATP stock solution were purchased from SignalChem. Radio-labeled [γ- 33 P ATP was purchased from PerkinElmer. 250 μL of HEK-293T soluble lysates (8 mg/mL), stably overexpressing WT, C22A or K45M MLTK were labeled for 1 h with 100 μM fragment or DMSO. The samples were then individually immunoprecipitated with 20 μL flag resin slurry per sample and then eluted with 15 μL 3×Flag-peptide. To each sample was added 5 μL of MBP and then 5 μL of γ- 33 P] ATP assay cocktail (250 μM, 167 μCi/mL) was added to initiate the kinase reaction. Each reaction mixture was incubated at ambient temperature for 30 min, and the reactions were terminated by spotting 25 μL of the reaction mixture onto individual precut phosphocellulose P81 paper. The spotted P81 strips were washed with 10 mL of 1% phosphoric acid (3×10 min). MLTK activity was measured by counting the radioactivity on the P81 paper in the presence of scintillation fluid in a scintillation counter. The background was determined from the K45M-inactive mutant MLTK activity level, which was subtracted from the WT and C22A samples. Relative activities for WT and C22A were normalized to their respective DMSO treated samples. Experiments were performed in triplicate. 
     CASP3 and CASP8 In Vitro Activity Assays 
     Caspase 3 and 8 assays were conducted with CASP8 activity assay kit (BioVision, K112-100) and Caspase 3 activity assay kit (Invitrogen, EnzChek® Caspase-3 Assay Kit), following the manufacturer&#39;s instructions. Briefly, recombinant Caspase 3 (10 μM) was added to soluble Ramos lysates (1 mg/mL) to a 100 nM final concentration of protease. Caspase 8 (30 μM) was added to soluble Ramos lysates to a 1 μM final concentration of protease. In triplicate, 50 μL lysate was treated with either DMSO, DEVD-CHO (“DEVD” disclosed as SEQ ID NO: 857) (20 μM) or the indicated compounds (100 μM) for 1 h. following which 50 μL of 2× reaction buffer containing 10 mM DTT and 5 μL substrate (4 mM stock in DMSO of IETD-AFC (“IETD” disclosed as SEQ ID NO: 858) for CASP8; 10 mM stock in DMSO of DEVD-AMC (“DEVD” disclosed as SEQ ID NO: 857) for CASP3) was added to each well and the samples were incubated at ambient temperature for 2 h. Caspase activity was measured from the increase in fluorescence (excitation 380 nm emission 460 nm). Experiments were performed in triplicate. Background was calculated from samples lacking the recombinant caspase. 
     Apoptosis Assays with Caspase 8 Inhibitors 
     4 mL of Jurkat cells in RPMI (1.5 million cells/mL) were treated with the indicated compound at 30 μM for 30 min (50 mM stock solution in DMSO). Z-VAD-FMK (EMD Millipore Biosciences, 627610) and was used at a final concentration of 100 μM. After pre-incubation, FASL (4 μL of 100 μg/μL stock solution of SuperFasLigand™ in water, final concentration=100 ng/mL, Enzo life Sciences) or staurosporine (8 μL of 1 mM stock solution in DMSO, final concentration=2 μM, Fisher Scientific, 50664333). After 6 hours, cells were harvested by centrifugation, washed and lysed in cell lysis buffer (BioVision, 1067-100) and 40 μg of each sample were separated by SDS-Page on 14% polyacrylamide gels. The gels were transferred to nitrocellulose membranes and were immunoblotted overnight with the indicated antibodies. For measurements of cell viability, in quadruplicate for each condition, 150,000 cells (100 μL of 1.5 million cells/mL) were plated in Nunc™ MicroWell™ 96-Well Optical-Bottom Plates with Polymer Base (Fisher Scientific). Compounds, FASL and STS were used at the same concentrations indicated above with a 30 minute pre-incubation with compound, followed by 6 hours with either STS or FASL or DMSO. Cell viability was measured with CellTiter-Glot® Luminescent Cell Viability Assay (Promega) and was read on a Biotech Synergy 4 plate reader. 
     Western Blotting 
     For CASP8, CASP3 and PARP, cell pellets were resuspended in cell lysis buffer from (BioVision, 1067-100) with 1× cOmplete protease inhibitor (Roche) and allowed to incubate on ice for 30 min prior to centrifugation (10 min, 16,000 g). For all other proteins, cell pellets were resuspended in PBS and lysed with sonication prior to centrifugation (10 min, 16,000 g). The proteins were then resolved by SDS-PAGE and transferred to nitrocellulose membranes, blocked with 5% BSA in TBST and probed with the indicated antibodies. The primary antibodies and the dilutions used are as follows: anti-parp (Cell Signaling, 9532, 1:1000), anti-casp3 (Cell Signaling, 9662, 1:500), anti-casp8 (Cell Signaling, 9746, 1:500), anti-IDH1 (Cell Signaling, 1:500, 3997s), anti-actin (Cell Signaling, 3700, 1:3000), anti-gapdh (Santa Cruz, sc-32233, 1:2000) anti-flag (Sigma Aldrich, F1804, 1:3000). Blots were incubated with primary antibodies overnight at 4° C. with rocking and were then washed (3×5 min, TBST) and incubated with secondary antibodies (LICOR, IRDye® 800CW or IRDye® 800LT, 1:10,000) for 1 h at ambient temperature. Blots were further washed (3×5 min, TBST) and visualized on a LICOR Odyssey Scanner. 
     Statistical Analysis 
     Data are shown as mean±SEM. P values were calculated using unpaired, two-tailed Student&#39;s t-test. P values of &lt;0.05 were considered significant. 
     Prediction Failures in Reactive Docking 
     Prediction failures were due to the approximations of the rigid model used with highly flexible/solvent exposed loop regions (STAT1:C255, PDB ID: 1YVL; HAT1:C101. PDB ID:2P0W; ZAP70:C117, PDB ID:4K2R), or with partially buried residues (SARS:C438, PDB ID:4187; PAICS:C374, PDB ID:2H31). In some embodiments, the simulation of some degree of flexibility (such as flexible side chains) improves the success rate. In some embodiments, the method was limited by availability and quality of crystallographic structures, when sequences were not fully resolved in available models (XPO1:C34, C1070, PDB ID:3GB8, FNBP1:C511,C555,C609, PDB ID:2EFL; IMPDH2:C140, PDB ID: INF7), or when only orthologue sequences were available (PRMT1:  R. norvegicus , PDB ID: 1ORI). 
     General Synthetic Methods 
     Chemicals and reagents were purchased from a variety of vendors, including Sigma Aldrich, Acros, Fisher, Fluka, Santa Cruz, CombiBlocks, BioBlocks, and Matrix Scientific, and were used without further purification, unless noted otherwise. Anhydrous solvents were obtained as commercially available pre-dried, oxygen-free formulations. Flash chromatography was carried out using 230-400 mesh silica gel. Preparative thin layer chromotography (PTLC) was carried out using glass backed PTLC plates 500-2000 μm thickness (Analtech). All reactions were monitored by thin layer chromatography carried out on 0.25 mm E. Merck silica gel plates (60F-254) and visualized with UV light, or by ninhydrin, ethanolic phosphomolybdic acid, iodine, p-anisaldehyde or potassium permanganate stain. NMR spectra were recorded on Varian INOVA-400, Bruker DRX-600 or Bruker DRX-500 spectrometers in the indicated solvent. Multiplicities are reported with the following abbreviations: s singlet; d doublet; t triplet; q quartet; p pentet; m multiplet; br broad. Chemical shifts were reported in ppm relative to TMS and J values were reported in Hz. Mass spectrometry data were collected on a HP 1100 single-quadrupole instrument (ESI; low resolution) or an Agilent ESI-TOF instrument (HRMS). 
     In some embodiments, General Procedure A was used for the synthesis of one or more of the small molecule fragments and/or cysteine-reactive probes described herein. The amine was dissolved in anhydrous CH 2 Cl 2  (0.2 M) and cooled to 0° C. To this, anhydrous pyridine (1.5 equiv.) was added in one portion, then chloroacetyl chloride (1.5 equiv.) dropwise and the reaction was monitored by TLC until complete disappearance of starting material and conversion to product was detected (typically 1 h). If the reaction did not proceed to completion, additional aliquots of pyridine (0.5 equiv.) and chloroacetyl chloride (0.5 equiv.) were added. The reaction was quenched with H 2 O (1 mL), diluted with CH 2 Cl 2  (20 mL), and washed twice with saturated NaHCO 3  (100 mL). The organic layer was concentrated in vacuo and purified by preparatory thin layer or flash column chromatography to afford the desired product. In some embodiments, General Procedure A1 is similar to General Procedure A except triethylamine (3 equiv.) was used instead of pyridine. In some embodiments, General Procedure A2 is similar to General Procedure A except N-methylmorpholine (3 equiv.) was used instead of pyridine. 
     In some embodiments, General Procedure B was used for the synthesis of one or more of the small molecule fragments and/or cysteine-reactive probes described herein. The amine was dissolved in anhydrous CH 2 Cl 2  (0.2 M) and cooled to 0° C. To this, triethylamine (TEA, 1.5 equiv.), was added in one portion, then acryloyl chloride (1.5 equiv.) dropwise, and the reaction was monitored by TLC until complete disappearance of starting material and conversion to product was detected (typically 1 h). If the reaction did not proceed to completion, additional aliquots of TEA (0.5 equiv.) and acryloyl chloride (0.5 equiv.) were added. The reaction was quenched with H 2 O (1 mL), diluted with CH 2 Cl 2  (20 mL), and washed twice with saturated NaHCO 3  (100 mL). The organic layer was passed through a plug of silica, after which, the eluant was concentrated in vacuo and purified by preparatory thin layer or flash column chromatography to afford the desired product. 
     In some embodiments, General Procedure C was used for the synthesis of one or more of the small molecule fragments and/or cysteine-reactive probes described herein. Acryloyl chloride (80.4 μL, 1.0 mmol, 2 equiv.) was dissolved in anhydrous CH 2 Cl 2  (4 mL) and cooled to 0° C. A solution of the amine (0.5 mmol, 1 equiv.) and N-methylmorpholine (0.16 mL, 1.5 mmol, 3 equiv.) in CH 2 Cl 2  (2 mL) was then added dropwise. The reaction was stirred for 1 hr at 0° C. then allowed to warm up to room temperature slowly. After TLC analysis showed disappearance of starting material, or 6 h, whichever was sooner, the reaction was quenched with saturated aqueous NaHCO 3 (5 mL) and extracted with CH 2 Cl 2  (3×10 mL). The combined organic layers were dried over anhydrous Na 2 SO 4 , concentrated in vacuo, and the residue obtained was purified by preparatory thin layer chromatography to afford the desired product. 
     Synthesis of Probes and Fragments 
     Purchased Fragments 
     The following electrophilic fragments were purchased from the indicated vendors. 2 (Santa Cruz Biotechnology sc-345083), 3 (Key Organics JS-092C), 4 (Sigma Aldrich T142433-10 mg), 6 (Toronto Research Chemicals M320600), 8 (Alfa Aesar H33763), 10 (Santa Cruz Biotechnology sc-345060), 11 (Santa Cruz Biotechnology sc-354895), 12 (Santa Cruz Biotechnology sc-354966), 21 (Santa Cruz Biotechnology, sc-279681), 22 (Sigma Aldrich 699357-5G), 26 (Sigma Aldrich T109959), 27 (Santa Cruz Biotechnology sc-342184), 28 (Santa Cruz Biotechnology sc-335173), 29 (Santa Cruz Biotechnology sc-348978), 30 (Santa Cruz Biotechnology sc-355362), 32 (Santa Cruz Biotechnology sc-354613), 33 (Sigma Aldrich R996505). 34 (Santa Cruz Biotechnology sc-355477), 35 (Santa Cruz Biotechnology sc-328985), 41 (Sigma Aldrich L469769), 42 (Sigma Aldrich R901946), 43 (Santa Cruz Biotechnology sc-307626), 52 (Enamine, EN300-08075), 55 (Santa Cruz Biotechnology sc-354880), 57 (VWR 100268-442), 58 (Enzo Life Sciences ALX-430-142-M005), 62 (WuXi Apptec). 
     Synthesis of Isotopically-Labeled TEV-Tags: 
     
       
         
         
             
             
         
       
     
     Isotopically-labeled heavy and light tags were synthesized with minor modifications to the procedure reported in Weerapana et al.  Nat Protoc  2:1414-1425 (2007) and Weerapana et al.  Nature  468:790-795 (2010). Fmoc-Rink-Amidc-MBHA resin (EMD Biosciences: 0.5 M, 830 mg, 0.6 mmol/g loading) was deprotected with 4-methylpiperidine in DMF (50% v/v, 2×5 mL, 1 min). Fmoc-Lys(N 3 )—OH (Anaspec) (500 mg, 1.26 mmol, 1.26 equiv.) was coupled to the resin overnight at room temperature with DIEA (113 μl) and 2-(6-chloro-1H-benzotriazol-1-yl)-1,1,3,3-tetramethylaminium hexafluorophosphate (HCTU; 1.3 mL of 0.5 M stock in DMF) followed by a second overnight coupling with Fmoc-Lys(N 3 )—OH (500 mg, 1.26 mmol, 1.26 equiv.), DIEA (113 μl), O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (HATU 1.3 mL of 0.5 M stock in DMF). Unmodified resin was then capped (2×30 min) with Ac 2 O (400 μL) and DIEA (700 μL) in DMF after which the resin was washed with DMF (2×1 min). Deprotection with 4-methylpiperidine in DMF (50% v/v, 2×5 mL, 1 min) and coupling cycles (4 equiv. Fmoc-protected amino acid (EMD biosciences) in DMF) with HCTU (2 mL, 0.5 M in DMF) and DIEA (347.7 μL) were then repeated for the remaining amino acids. For the heavy TEV-tag. Fmoc-Valine-OH ( 13 C 5 C 15 H 21   15 NO 4 ,  13 C 5 , 97-99,  15 N, 97-99%, Cambridge Isotope Laboratories, Inc.) was used. Reactions were monitored by ninhydrin stain and dual couplings were used for all steps that did not go to completion. Biotin (0.24 g, 2 equiv.) was coupled for two days at room temperature with NHS (0.1 g, 2 equiv.). DIC (0.16 g, 2 equiv.) and DIEA (0.175 g, 2 equiv.). The resin was then washed with DMF (5 mL, 2×1 min) followed by 1:1 CH 2 Cl 2 :MeOH (5 mL, 2×1 min), dried under a stream of nitrogen and transferred to a round-bottom flask. The peptides were cleaved for 90 minutes from the resin by treatment with 95:2.5:2.5 trifluoroacetic acid:water:triisopropylsilane. The resin was removed by filtration and the remaining solution was triturated with cold ether to provide either the light or heavy TEV-tag as a white solid. HPLC-MS revealed only minor impurities and the compounds were used without further purification. HRMS-ESI (m/z): calculated for C 83 H 128 N 23 O 23 S [M+H]: (Light-TEV-Tag) 1846.9268; found: 1846.9187; calculated for C 78   13 C 5 H 128 N 22   15 NO 23 S [M+H]: (Heavy-TEV-Tag): 1852.9237; found: 1852.9309. 
     Synthesis of Probes and Fragments 
     Synthesis of 1 
     
       
         
         
             
             
         
       
     
     N-(hex-5-yn-1-yl)-2-chloroacetamide (SI-1) 
     
       
         
         
             
             
         
       
     
     To a solution of 5-hexenylamine (63 mg, 0.65 mmol, 1.0 equiv.) in CH 2 Cl 2  (3.2 mL, 0.2 M) at 0° C. was added N-methylmorpholine (215 μL, 3 equiv.) followed by chloroacetic anhydride portionwise (222 mg, 2 equiv.). The reaction was allowed to come to room temperature and then stirred overnight. The reaction was then diluted with ether (50 mL), washed with 1 M HCl, 1 M NaOH, then brine (20 mL each). The combined organic layers were dried over magnesium sulfate and concentrated to yield chloroacetamide SI-1 (74 mg, 66%).  1 H NMR (400 MHz. Chloroform-d) δ 6.79 (s, 1H), 4.09 (d, J=1.1 Hz, 2H), 3.34 (q, J=6.8 Hz, 2H), 2.23 (td, J=6.9, 2.7 Hz, 2H), 1.98 (t J=2.7 Hz, 1H), 1.75-1.62 (m, 4H), 1.62-1.51 (m, 2H). 
     N-(hex-5-yn-1-yl)-2-iodoacetamide (1) 
     
       
         
         
             
             
         
       
     
     To a solution of chloroacetamide SI-1 (36.1 mg, 0.2 mmol) in acetone (1 mL, 0.2 M) was added sodium iodide (47 mg, 1.5 equiv.) and the reaction was stirred overnight. The next day the reaction was filtered through a plug of silica eluting with 20% ethyl acetate in hexanes, and the filtrate was concentrated to yield a 10:1 mixture of the desired iodoacetamide 1 and starting material. This mixture was re-subjected to the reaction conditions for one further day, at which point complete conversion was observed. The product was purified by silica gel chromatography, utilizing a gradient of 5 to 10 to 15 to 20% ethyl acetate in hexanes to yield the desired product (24 mg, 44%). In some embodiments, the reaction is performed with 2.5 equiv. of sodium iodide, in which case re-subjection is not necessary, and purification by PTLC is accomplished in 30% EtOAc/hexanes as eluent.  1 H NMR (500 MHz, Chloroform-d) δ 6.16 (s, 1H), 3.69 (s, 2H), 3.30 (q. J=6.8 Hz, 2H), 2.23 (td, J=6.8, 2.6 Hz, 2H), 1.97 (t, J=2.6 Hz, 1H), 1.75-1.61 (m, 2H), 1.61-1.52 (m, 2H). 
     N-(4-bromophenyl)-N-phe)-N-phenylacrylamide (5) 
     
       
         
         
             
             
         
       
     
     The title compound was synthesized according to General Procedure C from 4-bromophenylaniline (18.9 mg, 0.0762 mmol, 1 equiv.). Purification of the crude product by prep. TLC (30% EtOAc/hexanes) provided the title compound as a white solid (12.5 mg, 54%).  1 H NMR (500 MHz, Chloroform-d) δ 7.47 (d. J=8.2 Hz, 2H), 7.39 (t, J=7.6 Hz, 2H), 7.32 (d. J=7.4 Hz, 1H), 7.21 (d, J=7.7 Hz, 2H), 7.12 (d, J=8.2 Hz, 2H), 6.48 (d, J=16.7 Hz, 1H), 6.17 (dd, J=16.8, 10.3 Hz, 1H), 5.65 (d, J=10.3 Hz, 1H); HRMS-ESI (m/z) calculated for C 15 H 13 BrNO [M+H]: 302.0175; found: 302.0176. 
     Synthesis of 7 
     
       
         
         
             
             
         
       
     
     tert-butyl 4-(phenylaminopiperidine-1-carboxylate (SI-2) 
     
       
         
         
             
             
         
       
     
     SI-2 was prepared according to Thoma et al,  J. Med. Chem.  47:1939-1955 (2004).  1 H NMR (400 MHz, Chloroform-d) δ 7.24-7.12 (m, 2H), 6.75-6.68 (m, 1H), 6.66-6.58 (m, 2H), 3.88-3.81 (m, 1H), 3.44 (tt, J=10.4, 3.9 Hz, 2H), 3.00-2.88 (m, 2H), 2.10-1.99 (m, 2H), 1.48 (bs 9H), 1.41-1.27 (m, 2H). 
     tert-butyl 4-(2-chloro-N-phenylacetamido)piperidine-1-carboxylate (SI-3) 
     
       
         
         
             
             
         
       
     
     To a solution of aniline SI-2 (65 mg, 0.24 mmol) at 0° C. in CH 2 Cl 2  (0.6 mL) was added pyridine (38 μL, 2 equiv.) followed by chloroacetyl chloride (37.4 μL, 2.0 equiv.) in CH 2 Cl 2  (0.6 mL). The resulting solution was allowed to warm to room temperature and stirred overnight. The solution was then quenched with saturated aqueous sodium bicarbonate, extracted with Et 2 O (3×10 mL). The combined organic layers were dried over magnesium sulfate, filtered and concentrated to give an off-white solid, which was used without further purification (47 mg, 57%).  1 H NMR (400 MHz, Chloroform-d) δ 7.47-7.38 (m, 3H), 7.18-7.03 (m, 2H), 4.75-4.63 (m, 1H), 4.07 (s, 2H), 3.68 (s, 2H), 2.76 (s, 2H), 1.84-1.69 (m, 2H), 1.35 (s, 9H), 1.27-1.12 (m, 2H). 
     N-(1-benzoylpiperidin-4-yl)-2-chloro-N-phenylacetamide (7) 
     
       
         
         
             
             
         
       
     
     To neat SI-3 (47 mg, 0.128 mmol) was added trifluoroacetic acid (0.7 mL, final 0.2 M). The resulting solution was concentrated under a stream of nitrogen until no further evaporation was observed, providing the deprotected amine as its trifluoroacetate salt. This viscous gum was then treated with triethylamine in ethyl acetate (10% v/v, 2 mL; solution smokes upon addition). The resulting solution was concentrated to afford the free base, which contained only triethylammonium trifluoroacetate and the free amine by proton NMR. A stock solution was prepared by dissolving the resulting gum in CH 2 Cl 2  (1.2 mL, ˜0.1 M final). 
     The deprotected amine (0.3 mL of stock solution, 0.0319 mmol) was treated with Hunig&#39;s base (17.5 μL, 3 equiv.) and benzoyl chloride (7.6 μL, 2.0 equiv.). This solution was stirred overnight, quenched with saturated aqueous sodium bicarbonate, extracted with Et 2 O (3×10 mL). The resulting solution was dried over magnesium sulfate, filtered and concentrated. The resulting oil was purified by silica gel chromatography (20% EtOAc/hexanes) to afford chloroacetamide 7 as a white solid (8.6 mg, 75%).  1 H NMR (500 MHz, Chloroform-d) δ 7.55 (dd, J=5.5, 3.0 Hz, 3H), 7.50-7.32 (m, 5H), 7.21 (s, 2H), 4.92 (tt, J=12.3, 4.0 Hz, 1H), 4.87 (s, 1H), 3.87 (s, 1H), 3.78 (s, 2H), 3.21 (s, 1H), 2.97-2.90 (m, 1H), 2.01 (s, 1H), 1.90 (s, 1H), 1.45 (s, 1H), 1.36-1.26 (m, 1H), HRMS-ESI (m/z) calculated for C 20 H 22 ClN 2 O 2  [M+H]: 357.1364; found: 357.1362. 
     1-(4-benzylpiperidin-1-yl)-2-chloroethan-1-one (9) 
     
       
         
         
             
             
         
       
     
     Following General Procedure A, starting from 4-benzylpiperidine (840 mg, 5.2 mmol, 1 equiv.), the desired compound was obtained after column chromatography as a yellow oil (1 g, 81%). Spectroscopic data matches those reported previously reported in Papadopoulou et al.  J. Med. Chem.  55:5554-5565 (2012).  1 H NMR (500 MHz, Chloroform-d) δ 7.42-7.14 (m, 5H), 4.61 (d, J=13.4 Hz, 1H), 4.14 (q. J=21.9, 11.5 Hz, 2H), 3.89 (d, J=13.5, 1H), 3.11 (td, J=13.1, 2.7 Hz, 1H), 2.69-2.57 (m, 3H), 1.92-1.75 (m, 3H), 1.40-1.21 (m, 2H); HRMS-ESI (m/z) calculated for C 14 H 19 ClNO [M+H]: 252.115; found: 252.115. 
     N-(2-(1H-indol-3-yl)ethyl)-2-chloroacetamide (13) 
     
       
         
         
             
             
         
       
     
     Following General Procedure A, starting from tryptamine (400 mg, 2.5 mmol, 1 equiv.), the desired compound was obtained after column chromatography as a brownish solid (460 mg, 77%).  1 H NMR (500 MHz, Chloroform-d) δ 8.55 (s, 1H), 7.70 (d, J=7.9 Hz, 1H), 7.45 (d, J=8.1 Hz, 1H), 7.30 (t, J=7.5 Hz, 1H), 7.23 (t, J=7.4 Hz, 1H), 7.10 (s, 1H), 6.84 (s, 1H), 4.08 (s, 2H), 3.72 (q, J=6.4 Hz, 2H), 3.10 (t, J=6.8 Hz, 2H); HRMS-ESI (m/z) calculated for C 12 H 14 ClN 2 O 2 [M+H]: 237.0789; found: 237.0791. 
     N-(3,5-bis(trifluoromethyl)phenyl)acrylamide (14) 
     
       
         
         
             
             
         
       
     
     Following General Procedure B, starting from 3,5-bis(trifluoromethyl)aniline (1.16 g, 5 mmol, 1 equiv.), the desired compound was obtained after column chromatography as a white solid (1.05 g, 74%).  1 H NMR (500 MHz, Chloroform-d) δ 8.33 (s, 1H), 8.18 (s, 2H), 7.68 (s, 1H), 6.57 (d, J=17.5 Hz, 1H), 6.38 (dd, J=16.9, 10.3 Hz, 1H), 5.93 (d, J=12.5 Hz, 1H); HRMS-ESI (m/z) calculated for C 11 H 8 F 6 NO 2  [M+H]: 284.0505; found: 284.0504. 
     N-(4-phenoxy-3-(trifluoromethyl)phenyl)-N-(pyridin-3-ylmethyl)acrylamide (15) 
     
       
         
         
             
             
         
       
     
     4-phenoxy-3-(trifluoromethyl)aniline (260 mg, 1 mmol, 1 equiv.) (Combi-Blocks) was dissolved in TFA (5 mL). Following the reductive amination protocol reported by Boros et al.  J Org. Chem  74:3587-3590 (2009), the reaction mixture was cooled to 0° C. and to this sodium triacetoxyborohydride (STAB) (270 mg, 1.3 mmol, 1.3 equiv.) was added, 3-pyridinecarboxaldehyde (200 mg, 2 mmol, 2 equiv.) was dissolved in CH 2 Cl 2  (5 mL) and slowly added to the reaction mixture. Upon complete conversion to product, the reaction was diluted with CH 2 Cl 2  (20 mL) and washed with saturated sodium bicarbonate solution (3×20 mL) and the organic layer was dried then concentrated under reduced pressure. Without further purification the crude material was dissolved in anhydrous CH 2 Cl 2  and subjected to General Procedure B. The resulting crude was purified by prep. TLC to give a white solid (31 mg, 10%).  1 H NMR (500 MHz, Chloroform-d) δ 8.52 (d, J=3.5 Hz, 1H), 8.39 (s, 1H), 7.68 (d, J=7.8 Hz, 1H), 7.40 (t, J=7.7 Hz, 2H), 7.34 (s, 1H), 7.28-7.18 (m, 2H), 7.07 (d, J=8.2 Hz, 2H), 6.98 (d, J=7.5 Hz, 1H), 6.82 (d, J=8.8 Hz, 1H), 6.46 (d. J=16.8 Hz, 1H), 6.01 (dd, J=16.2, 10.7 Hz, 1H), 5.64 (d, J=10.3 Hz, 1H), 4.96 (s, 2H). HRMS-ESI (m/z) calculated for C 22 H 18 F 3 N 2 O 2  [M+H]: 399.1315; found: 399.1315. 
     Indoacetamide-rhodamine (16) 
     
       
         
         
             
             
         
       
     
     5-(and-6)-((N-(5-aminopentyl)amino)carbonyl)tetramethylrhodamine (tetramethylrhodamine cadaverine) mixed isomers (60 mg, 0.12 mmol, 1 equiv.) were dissolved in anhydrous DMF (500 μL) with sonication. To this was added DIPEA (60 μL, 0.34 mmol, 3 equiv.) and chloroacetyl chloride (10 μL, 0.13 mmol, 1 equiv., diluted 1:10 in DMF) and the reaction was stirred at room temperature for 20 min until complete conversion to the product was detected by TLC. The DMF was removed under a stream of nitrogen and the reaction mixture was separated by PTLC in MeOH:CH 2 Cl 2 :TEA (15:85:0.001). The chloroacetamide rhodamine was then eluted in MeOH:CH 2 Cl 2  (15:85), concentrated under reduced pressure and redissolved in acetone (500 μL). NaI (150 mg, 1 mmol, 10 equiv.) was added to this and the reaction was stirred for 20 min at 50° C. until complete conversion to product was detected and the crude reaction mixture was purified by reverse phase HPLC on a C18 column and concentrated to yield the title compound as a purple solid that is a mixture of 5 and 6 carboxamide tetramethylrhodamine isomers (ratio ˜6:1) (10 mg, 12%).  1 H NMR (600 MHz, Methanol-d 4 ) δ 8.87 (t, J=4.8 Hz, 0.14H), 8.80-8.71 (m, 1H), 8.41 (dd, J=8.2, 1.1 Hz, 0.86H), 8.35 (br s, 1H), 8.27 (dt, J=7.9, 1.5 Hz, 0.164H), 8.20 (dt, J=8.2, 1.5 Hz, 0.86H), 7.81 (s, 0.86H), 7.53 (d, J=7.8 Hz, 0.14H), 7.18-7.11 (m, 2H), 7.07 (d, J=9.5 Hz, 2H), 7.00 (s, 2H), 3.68-3.62 (m, 2H), 3.46-3.37 (m, 2H), 3.31 (s, 12H, obscured by solvent) 3.21-3.12 (m, 2H), 1.81-1.21 (m, 6H); HRMS-ESI (m/z) calculated for C 32 H 36 IN 4 O 5  [M+H]: 683.1725; found: 683.1716. 
     N-(3,5-bis(trifluoromethyl)phenyl)acetamide (17) 
     
       
         
         
             
             
         
       
     
     Following General Procedure A, starting with 3,5-bis(trifluoromethyl)aniline (327 mg, 1.42 mmol, 1 equiv.) and acetic anhydride (200 μL, 3 mmol, 2 equiv.), the title compound was obtained after PTLC as a white solid (302 mg, 78%).  1 H NMR (500 MHz, Chloroform-d) δ 8.10 (s, 2H), 7.72 (s, 1H), 7.68 (s, 1H), 2.32 (d, J=0.9 Hz, 3H). HRMS-ESI (m/z) calculated for C 11 H 8 F 6 NO 2  [M+H]: 284.0505; found: 284.0504. 
     Synthesis of 18 and 19 
     
       
         
         
             
             
         
       
     
     3-amino-N-(hex-5-yn-1-yl)-5-(trifluoromethyl)benzamide (SI-5) 
     
       
         
         
             
             
         
       
     
     To a solution of 3-amino-5-(trifluoromethyl)benzoic acid (74 mg, 0.36 mmol) in acetonitrile (3.6 mL, 0.1 M final) was added EDCI (83 mg, 1.2 equiv.) followed by hex-5-ynamine (35 mg, 1.0 equiv.) followed by 1-hydroxybenzotriazole hydrate (HOBt, 66.3 mg, 1.2 equiv.) and the resulting solution was stirred overnight. The reaction was diluted with ethyl acetate, washed with 1 M HCl twice and then brine. The organic layer was dried over magnesium sulfate and concentrated to yield aniline SI-5 (97.4 mg, 95%) as a white solid.  1 H NMR (400 MHz, Chloroform-d) δ 7.29-7.22 (m, 2H), 6.98 (t, J=1.8 Hz, 1H), 6.38 (t, J=5.5 Hz, 1H), 4.08 (s, 2H), 3.46 (td, J=7.1, 5.7 Hz, 2H), 2.25 (td, J=6.9, 2.6 Hz, 2H), 1.99 (t, J=2.7 Hz, 1H), 1.81-1.55 (m, 4H). 
     3-acrylamido-N-(hex-5-yn-1-yl)-5-(trifluoromethyl)benzamide (18) 
     
       
         
         
             
             
         
       
     
     Following General Procedure B, starting with SI-5 (42 mg, 0.15 mmol, 1 equiv.), the title compound was obtained after column chromatography as a white solid (34 mg, 70%).  1 H NMR (500 MHz, Chloroform-d) δ 8.94 (s, 1H), 8.24 (d, J=11.9 Hz, 2H), 7.71 (s, 1H), 6.87 (t, J=5.7 Hz, 1H), 6.55 (dd, J=17.4, 0.7 Hz, 1H), 6.43 (dd, J=16.9, 10.1 Hz, 1H), 5.88 (dd, J=10.1, 1.3 Hz, 1H), 3.56 (q, J=6.7 Hz, 2H), 2.33 (td, J=6.9, 2.7 Hz, 2H), 2.06 (t, J=2.7 Hz, 1H), 1.87 (p, 0.1=7.3 Hz, 2H), 1.69 (p, J=7.8 Hz, 2H); HRMS-ESI (m/z) calculated for C 17 H 18 F 3 N 2 O 2  [M+H]: 339.1314; found 339.1313. 
     3-acrylamido-N-(hex-5-yn-1-yl)-5-(trifluoromethyl)benzamide (19) 
     
       
         
         
             
             
         
       
     
     Synthesized according to General Procedure A2, starting from SI-5.  1 H NMR (600 MHz, Chloroform-d) δ 8.57 (s, 1H), 8.16 (t, J=1.8 Hz, 1H), 8.05 (t, J=1.8 Hz, 1H), 7.79 (d, J=2.0 Hz, 1H), 6.38 (d, J=6.1 Hz, 1H), 4.23 (s, 2H), 3.51 (td, J=7.1, 5.7 Hz, 2H), 2.27 (td. J=6.9, 2.7 Hz, 2H), 2.00 (t, J=2.6 Hz, 1H), 1.82-1.74 (m, 2H), 1.71-1.59 (m, 2H); HRMS-ESI (m/z) calculated for C 16 H 17 ClF 3 N 2 O 2  [M+H]: 361.0925; found: 361.0925. 
     2-chloro-1-(4-(hydroxydiphenylmethyl)piperidin-1-yl)ethan-1-one (20) 
     
       
         
         
             
             
         
       
     
     Following General Procedure A, starting with α,α-diphenyl-4-piperidinomethanol (800 mg, 3 mmol, 1 equiv.), the title compound was obtained after column chromatography as a white solid (637 mg, 61%).  1 H NMR (500 MHz, Chloroform-d) δ 7.56 (d, J=7.6 Hz, 4H), 7.39 (q, J=7.1 Hz, 4H), 7.28 (q, J=6.8 Hz, 2H), 4.66 (d, J=13.3 Hz, 1H), 4.07 (dd, J=12.2, 4.2 Hz, 2H), 3.91 (d, J=13.4 Hz, 1H), 3.18 (t, J=12.9 Hz, 1H), 2.77-2.62 (m, 3H), 1.67 (t. J=12.5 Hz, 2H), 1.56 (q, J=11.8 Hz, 1H), 1.44 (q, J=12.4, 11.8 Hz, 1H); HRMS-ESI (m/z) calculated for C 20 H 23 ClNO 2  [M+H]: 344.1412; found: 344.1412. 
     (E)-3-(3,5-bis(trifluoromethyl)phenyl)-2-cyanoacrylamide (23) 
     
       
         
         
             
             
         
       
     
     3,5-bis(trifluoromethyl)benzaldehyde (880 mg, 3.6 mmol, 1 equiv.) and 2-cyanoacetamide (460 mg, 5.5 mmol, 1.5 equiv.) were dissolved in MeOH (10 mL). To this was added piperidine (214 mg, 0.7 equiv.) and the reaction was stirred at room temperature for 30 minutes at which point starting material was consumed. After addition of an equivalent volume of water (10 mL), the precipitate was collected by filtration and washed with water/methanol (1:1) to yield the title compound as a white solid (534 mg, 47%);  1 H NMR (400 MHz, Acetone-d 6 ) δ 8.78 (s, 2H), 8.61 (s, 1H), 8.41 (s, 1H), 7.57 (s, 1H), 7.42 (s, 1H); HRMS-ESI (m/z) calculated for C 12 H 2 F 6 N 2 O 2  [M+H]: 309.0457; found: 309.0459. 
     N-(3,5-bis(trifluoromethyl)phenyl)-2-bromopropanamide (24) 
     
       
         
         
             
             
         
       
     
     Following General Procedure A1, starting with 3,5-bis(trifluoromethyl)aniline (250 mg, 1.1 mmol, 1 equiv.) and 2-bromopropionyl chloride (200 μL, 2 mmol, 1.8 equiv.) the title compound was obtained by PTLC as a white solid (130 mg, 35%).  1 H NMR (500 MHz, Chloroform-d) δ 8.34 (s, 1H), 8.06 (s, 2H), 7.66 (s, 1H), 4.58 (q, J=7.0 Hz, 1H), 1.98 (d, J=7.0 Hz, 3H); HRMS-ESI (m/z) calculated for C 11 H 7 BrF 6 NO [M−H]: 361.9621; found: 361.9623. 
     N-(3,5-bis(trifluoromethyl)phenyl)-2-chloropropanamide (25) 
     
       
         
         
             
             
         
       
     
     Following General Procedure A1, starting with 3,5-bis(trifluoromethyl)aniline (327 mg, 1.42 mmol, 1 equiv.) and 2-chloropropionyl chloride (200 μL, 2 mmol, 1.8 equiv.) the title compound was obtained by PTLC as a white solid (250 mg, 55%).  1 H NMR (500 MHz, Chloroform-d) δ 8.61 (s, 1H), 8.16 (s, 2H), 7.75 (s, 1H), 4.67 (q, J=7.1 Hz, 1H), 1.93 (d, J=7.1 Hz, 3H). HRMS-ESI (m/z) calculated for C 11 H 7 ClF 6 NO [M−H]: 318.0126; found: 318.0126. 
     N-(3,5-bis(trifluoromethyl)phenyl)-N-(pyridin-3-ylmethyl)acrylamide (31) 
     
       
         
         
             
             
         
       
     
     3,5-bis(trifluoromethyl)aniline (350 mg, 1.6 mmol, 1 equiv.) was dissolved in TFA (5 mL). The reaction mixture was cooled to 0° C. and to this sodium triacetoxyborohydride (STAB) (400 mg, 2 mmol, 1.3 equiv.) was added, 3-pyridinecarboxaldehyde (244 mg, 1.5 mmol, 1 equiv.) was dissolved in CH 2 Cl 2  (5 mL) and slowly added to the reaction mixture dropwise over 10 minutes. Upon complete conversion to product, the reaction mixture was diluted with CH 2 C2 (20 mL) and washed with saturated sodium bicarbonate solution (3×20 mL) and the organic layer was dried then concentrated under reduced pressure. Without further purification the crude material was dissolved in anhydrous CH 2 Cl 2  and subjected to General Procedure B. The resulting crude was purified by PTLC to give a white solid (10 mg, 2%).  1 H NMR (500 MHz, Chloroform-d) δ 8.63 (d. J=3.8 Hz, 1H), 8.49 (s, 1H), 7.93 (s, 1H), 7.70 (d, J=7.7 Hz, 1H), 7.55 (s, 2H), 7.35 (dd, J=7.6, 5.3 Hz, 1H), 6.60 (dd, J=16.6, 1.6 Hz, 1H), 6.02 (dd, J=16.9, 10.2 Hz, 1H), 5.79 (dd, J=10.3, 1.6 Hz, 1H), 5.11 (s, 2H). HRMS-ESI (m/z) calculated for C 17 H 13 F 6 N 2 O [M+H]: 375.0927; found: 375.0928. 
     3-(2-chloroacetamido)-5-trifluoromethyl)benzoic acid (36) 
     
       
         
         
             
             
         
       
     
     To a solution of 3-amino-5-(trifluoromethyl)benzoic acid (500 mg, 2.44 mmol) in 1.5 mL of dimethylacetamide (1.6 M) at 0° C. was added chloroacetyl chloride (214 μL, 2.69 mmol, 1.1 equiv.). The resulting solution was warmed to ambient temperature and stirred for 20 minutes, at which point ethyl acetate (40 mL) and water (30 mL) were added. The pH of the aqueous layer was adjusted to pH 10 via addition of 1 N NaOH, and the phases were separated. The aqueous layer was washed with 40 mL of ethyl acetate, then acidified by adding 1 N HCl. The product was extracted with ethyl acetate (40 mL), and the organic layer was washed with IM HCl (2×40 mL), brine (40 mL), dried over magnesium sulfate and concentrated to provide the desired product (456 mg, 66%).  1 H NMR (500 MHz, Chloroform-d) δ 8.31 (s, 1H), 8.27 (s, 1H), 8.14 (s, 1H), 4.13 (s, 2H); HRMS-ESI (m/z) calculated for C 10 H 8 ClF 3 NO 3  [M+H]: 282.0139; found: 282.0141. 
     1-(4-(5-fluorobenzisoxazol-3-yl)piperidin-1-yl)prop-2-en-1-one (37) 
     
       
         
         
             
             
         
       
     
     The title compound was obtained starting from 6-fluoro-3(4-piperidinyl)-1,2-benzisoxazole hydrochloride (53 mg, 0.2 mmol, 1 equiv.) according to General Procedure C as a colorless oil (49.1 mg, 87%).  1 H NMR (400 MHz, Chloroform-d) δ 7.64 (dd, J=8.7, 5.1 Hz, 1H), 7.27 (dd, J=8.4, 2.3 Hz, 1H), 7.08 (td, J=8.9, 2.1 Hz, 1H), 6.64 (dd, J=16.8, 10.6 Hz, 1H), 6.32 (dd, J=16.9, 1.9 Hz, 1H), 5.73 (dd, J=10.6, 1.9 Hz, 1H), 4.70 (d, J=13.4 Hz, 1H), 4.15 (d, J=12.4 Hz, 1H), 3.53-3.13 (m, 2H), 2.99 (t, J=13.1 Hz, 1H), 2.25-2.07 (m, 2H), 2.00 (ddd, J=23.1, 14.2, 7.8 Hz, 2H); HRMS-ESI (m/z) calculated for C 15 H 16 FN 2 O [M+H]: 275.119; found: 275.119. 
     tert-butyl 4-(4-acrylamido-2,6-difluorophenyl)piperazine-1-carboxylate (38) 
     
       
         
         
             
             
         
       
     
     The title compound was obtained starting from tert-Butyl 4-(4-amino-2,6-difluorophenyl)piperazine-1-carboxylate according to General Procedure B.  1 H NMR (400 MHz, Chloroform-d) δ 8.12 (s, 11), 7.13 (d, J=10.4 Hz, 2H), 6.36 (d, J=16.9 Hz, 11), 6.19 (dd, J=16.8, 10.2 Hz, 1H), 5.70 (d, J=10.2 Hz, 1H), 3.45 (t, J=4.7 Hz, 4H), 3.00 (t, J=3.7 Hz, 4H), 1.41 (s, 9H); HRMS-ESI (m/z) calculated for C 18 H 24 F 2 N 3 O 3 [M+H]: 368.178; found: 368.178. 
     N-(4-bromo-2,5-dimethylphenyl)acrylamide (40) 
     
       
         
         
             
             
         
       
     
     Following General Procedure B, starting from 4-bromo-2,5-dimethylaniline (900 mg, 4.5 mmol, 1 equiv.), the title compound was obtained after column chromatography and recrystallization from cold CH 2 Cl 2  as a white solid (611 mg, 40%).  1 H NMR (500 MHz, Chloroform-d) δ 7.87 (s, 1H), 7.43 (s, 1H), 7.16 (s, 1H), 6.50 (d, J=16.7 Hz, 1H), 6.35 (dd, J=16.4, 10.3 Hz, 1H), 5.86 (d, J=10.3 Hz, 1H), 2.42 (s, 3H), 2.28 (s, 3H); HRMS-ESI (m/z) calculated for C 11 H 13 BrNO [M+H]: 254.0175; found: 254.0175. 
     2-Chloroacetamido-2-deoxy-α/β-D-glucopyranose (44) 
     
       
         
         
             
             
         
       
     
     To a stirred solution of hexosamine hydrochloride (590 mg, 3.39 mmol, 1 equiv.) in anhydrous MeOH (200 mL) at room temperature was added sodium metal (60 mg, 2.6 mmol, 0.78 equiv.), TEA (400 μL, 5.7 mmol, 1.8 equiv.). Chloroacetic anhydride (1 g, 5.9 mmol, 1 equiv.) was then added and the mixture stirred for 6 h, monitoring for completeness by TLC. After which, the reaction mixture was concentrated in vacuo. The crude product then was purified by two rounds of column chromatography to afford the pure title product as a white solid (610 mg, 72%).  1 H NMR (500 MHz, Methanol-d 4 ) δ 5.20 (d, J=3.7 Hz, 1Hα), 4.75 (d, J=8.3 Hz, 1Hβ), 4.19 (dd, J=20.2, 13.9 Hz, 2H), 4.19 (d, J=12.6 Hz, 1H), 3.95 (dd. J=10.6, 3.5 Hz, 1Hα), 3.83 (m, 3Hα, 3Hβ), 3.74 (d, J=5.1 Hz, 1Hβ), 3.70 (dd, J=11.4, 8.9 Hz, 1Hβ), 3.60 (dd, J=10.7, 9.5 Hz, 1Hβ), 3.46 (t, J=9.3 Hz, 11), 3.42 (t, J=10.0 Hz, 1Hβ); HRMS-ESI (m/z) calculated for C 8 H 15 ClNO 6  [M+H]: 256.0582; found: 256.0582. 
     2-chloro-1-(2-methyl-3,4-dihydroquinolin-1(2H)-yl)ethan-1-one (45) 
     
       
         
         
             
             
         
       
     
     Chloroacetyl chloride (80.4 μL, 0.9 mmol, 1.7 equiv.) was dissolved in anhydrous CH 2 Cl 2  (3 mL) and cooled to 0° C. A solution of 2-methyl-1,2,3,4-tetrahydroquinoline (80.1 mg, 0.544 mmol, 1 equiv.) and N-methylmorpholine (0.11 mL, 1.0 mmol, 1.8 equiv.) in CH 2 Cl 2  (2 mL) was then added dropwise. After 6 h, the reaction was quenched with saturated aqueous NaHCO 3  (5 mL) and extracted with CH 2 Cl 2  (3×10 mL). The combined organic layers were dried over anhydrous Na 2 SO 4  and concentrated under reduced pressure. The resultant residue was purified by prep. TLC (30% EtOAc/hexanes), providing the title compound as an off-white solid (108.8 mg, 89%).  1 H NMR (400 MHz, chloroform-d) δ 7.30-7.13 (m, 4H), 4.86-4.75 (m, 1H), 4.20 (d, J=12.5 Hz, 1H), 4.09 (d, J=12.5 Hz, 1H), 2.69-2.58 (m, 1H), 2.59-2.46 (m, 1H), 2.46-2.31 (m, 1H), 1.36-1.29 (m, 1H), 1.15 (d, J=6.5 Hz, 3H); HRMS-ESI (m/z) calculated for C 12 H 15 ClNO [M+H]: 224.0837; found: 224.0836. 
     N-cyclohexyl-N-phenylacrylamide (46) 
     
       
         
         
             
             
         
       
     
     The title compound was synthesized according to General Procedure C from N-cyclohexylaniline (89.5 mg, 0.511 mmol, 1 equiv.). Purification of the crude product by flash column chromatography (10-20% EtOAc/hexanes) then prep. TLC (30% EtOAc/hexanes) provided the title compound as an off-white solid (53.1 mg, 45%).  1 H NMR (400 MHz, chloroform-d) δ 7.42-7.33 (m, 3H), 7.10-7.06 (m, 2H), 6.31 (dd, J=16.7, 2.1 Hz, 1H), 5.77 (dd, J=16.7, 10.3 Hz, 1H), 5.41 (dd, J=10.4, 2.1 Hz, 1H), 4.65 (tt, J=12.2, 3.7 Hz, 1H), 1.85 (dt, J=11.2, 1.8 Hz, 2H), 1.75-1.68 (m, 2H), 1.61-1.53 (m, 1H), 1.40 (qt, J=13.3, 3.6 Hz, 2H), 1.07 (qd, J=12.4, 3.6 Hz, 2H), 0.91 (qt, J=13.1, 3.8 Hz, 1H); HRMS-ESI (m/z) calculated for C 15 H 20 NO [M+H]: 230.1539; found: 230.1539. 
     1-(5-bromoindolin-1-yl)prop-2-en-1-one (47) 
     
       
         
         
             
             
         
       
     
     The title compound was synthesized according to General Procedure C from 5-bromoindoline (41.7 mg, 0.211 mmol, 1 equiv.), acryloyl chloride (32 μL, 0.40 mmol, 1.9 equiv.), and changing the base to pyridine (32 μL, 0.40 mmol, 1.9 equiv.). Purification of the crude product by re-precipitation from EtOAc provided the title compound as a white solid (67.8 mg, 64%).  1 H NMR (400 MHz, chloroform-d) δ 8.16 (d, J=8.6 Hz, 1H), 7.33-7.25 (m, 2H), 6.60-6.42 (m, 2H), 5.84-5.76 (m, 1H), 4.15 (t, J=8.6 Hz, 2H), 3.17 (t, J=8.6 Hz, 2H); HRMS-ESI (m/z) calculated for C 11 H 11 BrNO [M+H]: 252.0018; found: 252.0017. 
     N-(1-benzylpiperidin-4-yl)-N-phenylacrylamide (48) 
     
       
         
         
             
             
         
       
     
     The title compound was synthesized according to General Procedure C from 1-benzyl-N-phenylpiperidin-4-amine (30.0 mg, 0.113 mmol, 1 equiv.), acryloyl chloride (17 μL, 0.21 mmol, 1.9 equiv.), and changing the base to pyridine (17 μL, 0.21 mmol, 1.9 equiv.). Purification of the crude product by prep. TLC provided the title compound as a white solid (22.5 mg, 64%).  1 H NMR (400 MHz, chloroform-d) δ 7.62-7.56 (m, 2H), 7.43-7.36 (m, 6H), 7.05 (d, J=6.2 Hz, 2H), 6.29 (dd, J=16.8, 2.1 Hz, 1H), 5.79 (dd, J=16.8, 10.3 Hz, 1H), 5.46 (dd, J=10.3, 2.1 Hz, 1H), 4.81-4.70 (m, 1H), 4.09 (s, 2H), 3.41 (d, J=12.0 Hz, 2H), 2.82 (q, J=11.5 Hz, 2H), 2.21 (q. J=11.9 Hz, 2H), 1.94 (d, J=14.2 Hz, 2H); HRMS-ESI (m/z) calculated for C 21 H 25 N 2 O [M+H]: 321.1961; found: 321.1962. 
     2-chloro-N-(2-methyl-5-(trifluoromethyl)phenyl)acetamide (49) 
     
       
         
         
             
             
         
       
     
     The title compound was synthesized according to General Procedure A1 from 2-methyl-5-(trifluoromethyl)aniline (35.0 mg, 0.2 mmol, 1 equiv.). Purification of the crude product by prep. TLC (20% EtOAc/hexanes) provided the title compound as a white solid (48.2 mg, 95%).  1 H NMR (600 MHz, chloroform-d) δ 8.31 (s, 1H), 8.25 (d, J=1.9 Hz, 1H), 7.37 (dd, J=7.9, 1.8 Hz, 1H), 7.32 (d, J=7.9 Hz, 1H), 4.25 (s, 2H), 2.36 (s, 3H); HRMS-ESI calculated for C 10 H 10 ClF 3 NO [M+H]: 252.0397; found: 252.0397. 
     1-(5-bromoindolin-1-yl)-2-chloroethan-1-one (50) 
     
       
         
         
             
             
         
       
     
     The title compound was synthesized according to General Procedure A1 from 5-bromoindoline (39.6 mg, 0.2 mmol, 1 equiv.). Purification of the crude product by prep. TLC (25% EtOAc/hexanes) provided the title compound as an off-white solid (48.6 mg, 89%).  1 H NMR (600 MHz, CDCl 3 ) δ 8.07 (d, J=8.4 Hz, 1H), 7.32 (d, J=8.8 Hz, 2H), 4.17 (t, J=8.6 Hz, 2H), 4.14 (s, 2H), 3.22 (t, J=8.4 Hz, 2H); HRMS-ESI (m/z) calculated for C 10 H 10 BrClNO [M+H]: 273.9629; found: 273.9629. 
     2-chloro-N-(quinolin-5-yl)acetamide (51) 
     
       
         
         
             
             
         
       
     
     To a stirring suspension of 5-aminoquinoline (28.8 mg, 0.2 mmol, 1 equiv.) and potassium carbonate (82.9 mg, 0.6 mmol, 3 equiv.) in anhydrous CH 2 Cl 2  (3 mL) at 0° C. was added chloroacetyl chloride (24 μL, 1.5 equiv.). The reaction was allowed to slowly warm up to room temperature. After 3 hours, the mixture was filtered, washed with EtOAc (10 mL) and CH 2 Cl 2  (10 mL). The solid cake was then eluted with MeOH (20 mL) and the filtrate concentrated in vacuo. The residue was taken up in 10% MeOH/CH 2 Cl 2  and passed through a pad of silica to provide the title compound as an off-white solid (42.6 mg, 82%).  1 H NMR (500 MHz, CDCl 3 ) δ 8.96 (d. J=2.5 Hz, 1H), 8.71 (s, 1H), 8.20 (d, J=8.6 Hz, 1H), 8.04 (d, J=8.5 Hz, 1H), 7.94 (d, J=7.5 Hz, 1H), 7.74 (t, =8.0 Hz, 1H), 7.48 (dd, J=8.5, 4.2 Hz, 1H), 4.35 (s, 2H); HRMS-ESI (m/z) calculated for C 11 H 9 ClN 2 O [M+H]: 221.0476; found: 221.0477. 
     1-(4-benzylpiperidin-1-yl)prop-2-en-1-one (53) 
     
       
         
         
             
             
         
       
     
     Following General Procedure B, starting from 4-benzylpiperidine (1 g, 5.7 mmol, 1 equiv.), the title compound was obtained after column chromatography as a yellow oil (748 mg, 57%).  1 H NMR (500 MHz, Chloroform-d) δ 7.36 (t, J=7.4 Hz, 2H), 7.28 (t, J=7.4 Hz, 1H), 7.20 (d, J=7.1 Hz, 2H), 6.64 (dd, J=16.8, 10.6 Hz, 1H), 6.32 (dd, J=16.8, 1.9 Hz, 1H), 5.72 (dd, J=10.6, 1.9 Hz, 1H), 4.72 (d, J=12.7 Hz, 1H), 4.03 (d, J=13.0 Hz, 1H), 3.05 (t, J=12.7 Hz, 1H), 2.70-2.59 (m, 3H), 1.86 (ddp, J=14.6, 7.2, 3.5 Hz, 1H), 1.77 (m, 2H), 1.37-1.18 (m, 2H); HRMS-ESI (m/z) calculated for C 15 H 20 ClNO [M+H]: 230.1539; found: 230.1539. 
     2-chloro-N-((3-hydroxy-5-(hydroxymethyl)-2-methylpyridin-4-yl)methyl)acetamide (54) 
     
       
         
         
             
             
         
       
     
     To a stirred solution of pyridoxamine hydrochloride (150 mg, 0.64 mmol, 1 equiv.) in anhydrous MeOH (20 mL) at room temperature was added sodium metal (30 mg, 1.5 mmol, 2.3 equiv.), TEA (100 μL, 1 mmol, 1.6 equiv.). Chloroacetic anhydride (390 mg, 2.29 mmol, 3.5 equiv.) was added and the mixture stirred for 6 h, monitoring for completeness by TLC. After which, the reaction mixture was concentrated in vacuo. The crude product then was the purified by prep. TLC to afford the title compound as a white solid (46 mg, 30%).  1 H NMR (500 MHz, Methanol-d 4 ) δ 7.97 (s, 1H), 4.81 (s, 2H), 4.61 (s, 2H), 4.17 (s, 3H), 4.06 (s, 1H), 3.35 (s, 1H), 2.52 (s, 3H); HRMS-ESI (m/z) calculated for C 10 H 14 ClN 2 O 3 [M+H]: 245.0687; found: 245.0688. 
     1-(6,7-dimethoxy-3,4-dihydroisoquinolin-2(1H)-yl)prop-2-en-1-one (56) 
     
       
         
         
             
             
         
       
     
     To a stirring suspension of the 6,7-dimethoxy-3,4-dihydroisoquinoline (1 g, 5.2 mmol, 1 equiv.) and TEA (1800 μL, 12.6 mmol, 2.5 equiv.) in anhydrous THF (10 mL) at 0° C. was added acryloyl chloride (1320 μL, 13.2 mmol, 2.6 equiv.) and the reaction was allowed to slowly warm up to room temperature. After 2 hours, the mixture was diluted with CH 2 Cl 2  (2×50 mL) and washed with saturated brine (2×50 mL) and the combined organics were concentrated in vacuo. The residue was taken up in 10% MeOH/CH 2 Cl 2  and purified by column chromatography to afford the title compound as a white solid (700 mg, 54%, mixture of E/Z isomers).  1 H NMR (500 MHz, Chloroform-d) δ 6.63 (m, 3H), 6.29 (d, J=16.8 Hz, 1H), 5.69 (dd, J=10.6, 1.8 Hz, 1H), 4.69 (s, 1H [major]), 4.63 (s, 0.8H [minor]), 3.82 (s, 7H), 3.73 (t, J=5.6 Hz, 1H), 2.84-2.77 (m, 2H); HRMS-ESI (m/z) calculated for C 14 H 18 NO 3  [M+H]: 248.128; found: 248.1281. 
     2-chloro-N-(1-(3-ethynylbenzoyl)piperidin-4-yl)-N-phenylacetamide (61) 
     
       
         
         
             
             
         
       
     
     To an excess of neat SI-3 was added 0.7 mL of trifluoroacetic acid (0.2 M). The resulting solution was concentrated under a stream of nitrogen until no further evaporation was observed, providing the deprotected amine as its trifluoroacetate salt. The trifluoroacetate amine salt (90.6 mg, 0.25 mmol) was taken up in DMF (0.5 mL, 0.5 M) and the resulting solution was cooled to 0° C. 3-ethynyl benzoic acid (44 mg, 1.2 equiv.), HATU (113 mg, 1.2 equiv.), and Hunig&#39;s base (86 μL, 2 equiv.) were sequentially added. The reaction was stirred for 2 hours at 0° C., diluted with Et 2 O, and then washed with 1 M HCl. The organic layer was dried over magnesium sulfate, concentrated, and purified by flash chromatography (gradient from 40 to 70% ethyl acetate in hexanes) to provide the title compound (87 mg, 92%).  1 H NMR (400 MHz, Chloroform-d) δ 7.51 (dd, J=9.5, 5.4 Hz, 4H), 7.43 (d. J=1.9 Hz, 1H), 7.39-7.25 (m, 2H), 7.14 (d, J=10.4 Hz, 2H), 4.86 (tt, J=15.1, 5.3 Hz, 2H), 3.72 (s, 3H), 3.19 (d, J=14.0 Hz, 1H), 3.11 (s, 1H), 2.86 (s, 1H), 1.90 (d, J=36.6 Hz, 2H), 1.38 (s, 1H), 1.24 (d, J=19.9 Hz, 1H); HRMS-ESI (m/z) calculated for C 22 H 22 ClN 2 O 2 [M+H]: 381.1364; found: 381.1363. 
     Global Profiling of Cysteine-Reactive Fragments in Native Populations 
     Cysteine is unique among protein-coding amino acids owing to its high nucleophilicity and sensitivity to oxidative modification. Cysteine residues perform catalytic functions in diverse enzyme classes and represent sites for post-translational regulation of proteins through disulfide bonding, iron-sulfur cluster formation, conversion to sulfinic and sulfonic acid, nitrosylation, S-glutathionylation and lipid modification. Using a quantitative chemical proteomic method termed isoTOP-ABPP (isotopic Tandem Orthogonal Proteolysis-Activity-Based Protein Profiling), global measurements of the intrinsic reactivity of cysteine residues was carried out and their sensitivity to modification by lipid-derived electrophiles was assessed. In order to determine whether isoTOP-ABPP was adapted to perform covalent FBLD in native biological systems, a cell preparation (lysate or intact cells) was pre-treated with DMSO or one member of a library of electrophilic small-molecule fragments and then exposed to a broad-spectrum cysteine-reactive probe iodoacetamide (IA)-alkyne 1 ( FIG. 1A ). Proteins harboring IA-alkyne-labeled cysteine residues from DMSO- and fragment-treated samples were conjugated by copper-mediated azide-alkyne cycloaddition (CuAAC or click) chemistry to isotopically differentiated azide-biotin tags (heavy and light, respectively), combined, enriched by streptavidin, and proteolytically digested on-bead to yield isotopic peptide pairs that were analyzed by LC-MS. Quantification of MS1 chromatographic peak ratios for peptide pairs identified fragment-competed Cys residues as those displaying high competition ratios, or R values, in DMSO/fragment comparisons. 
     A 50+ member fragment library was constructed with most compounds containing either a chloroacetamide or acrylamide electrophile ( FIG. 1B  and  FIG. 3 ), which are well-characterized cysteine-reactive groups found in many chemical probes and some clinically approved drugs. These electrophiles were appended to structurally diverse small-molecule fragments (&lt;300 Da) intended to serve as recognition elements that promote interactions with different subsets of the human proteome. The library also contained some additional electrophiles, such as cyanoacrylamides and vinylsulfonamides, and known bioactive electrophilic compounds (e.g., the anti-cancer agent piperlongumine and anti-migratory agent locostatin) ( FIG. 1B , and  FIG. 3 ). The electrophile library was screened at a high concentration (500 μM) comparable to the ligand concentrations used in typical FBLD experiments. A subset of the fragment library was initially assayed by competitive profiling in a human MDA-MB-231 breast cancer cell line proteome using an IA-rhodamine probe 16, which permitted facile SDS-PAGE detection of cysteine reactivity events. This experiment identified several proteins that showed reductions in IA-rhodamine labeling in the presence of one or more fragments ( FIG. 1C , asterisks). Interestingly, the proteins exhibited distinct SARs across the test fragment set, indicating that the library recognition elements exert a strong influence over specific fragment-protein reactivity events. 
     Competitive isoTOP-ABPP was used to globally map human proteins and the cysteine residues within these proteins that were targeted by fragment electrophiles. Each fragment was tested, in general, against two distinct human cancer cell proteomes (MDA-MB-231 and Ramos cells) and most fragments were screened in duplicate against at least one of these proteomes. On average, 927 cysteines were quantified per data set, and it was required that individual cysteines were quantified in at least three data sets for interpretation. Based on these criteria, more than 6157 cysteines from 2885 proteins were quantified in aggregate across all data sets with an average quantification frequency of 22 data sets per cysteine ( FIG. 4A ). Fragment-competed cysteine residues, or “liganded” cysteines, were defined as those showing ≥75% reductions in IA-alkyne labeling (R values≥4 for DMSO/fragment). To minimize the potential for false-positives, only cysteines that showed R values≥4 in two or more data sets and met additional criteria for data quality control were considered as targets of the fragment electrophiles. The proteomic reactivity values, or liganded cysteine rates, of individual fragments were then calculated as the percentage of liganded/total quantified cysteines in isoTOP-ABPP experiments performed on that fragment. 
     Most fragment electrophiles showed a tempered reactivity across the human proteome, with a median liganded cysteine rate of 3.8% for the library ( FIG. 4B ). Substantial differences in reactivity were, however, observed, with individual electrophiles showing liganded cysteine rates of &lt;0.1% and others displaying rates &gt;15% ( FIG. 4B ). That piperlongumine and locostatin fell into the latter category indicated the intrinsic proteomic reactivity of the fragment electrophiles did not, in general, exceed that of previously described electrophilic probes. A subset of fragments was also screened at lower concentrations (25-50 μM), which confirmed that their proteomic reactivities were concentration-dependent ( FIG. 4C ). The relative reactivity of fragment electrophiles was similar in MDA-MB-231 and Ramos cell proteomes ( FIG. 4D ), indicating that this parameter is an intrinsic property of the compounds. Fragments also showed consistent reactivity profiles when assayed in biological replicate experiments ( FIG. 4E ). Interestingly, it was found that the proteomic reactivity of fragment electrophiles was only marginally correlated with their glutathione adduction potential, which is a commonly used surrogate assay for measurements of proteinacious cysteine reactivity ( FIG. 4F ). These differences are attributed to the impact of the recognition element of fragment electrophiles on their interactions and, ultimately, reactivity with proteins. 
     A comparison of fragments 3, 14, 17, and 23-26 provided insights into the relative proteomic reactivity of different electrophilic groups coupled to a common recognition element (3,5-di(trifluoromethyl)phenyl group). Chloroacetamide 3 exhibited greater reactivity than acrylamide 14 (15% versus 3.4% liganded cysteines, respectively;  FIG. 1D ), with cyanoacrylamide 23 exhibiting similar reactivity to acrylamide 14 and other, more sterically congested electrophiles (24-26) showing reduced proteomic reactivity ( FIG. 4G ). Importantly, the non-electrophilic acetamide control fragment 17 showed negligible activity in competitive isoTOP-ABPP experiments (liganded cysteine rate &lt;0.2%) ( FIG. 1D ), indicating that the vast majority of detected fragment-cysteine interactions reflected covalent reactions versus non-covalent binding events. Also in support of this conclusion, “clickable” alkyne analogues of 3 and 14 (compounds 19 and 18, respectively) exhibited different concentration-dependent proteome labeling profiles (19&gt;18;  FIG. 1E ) that mirrored the respective liganded cysteine rates displayed by 3 and 14 in competitive isoTOP-ABPP experiments (3&gt;14;  FIG. 1D ). Despite the greater overall proteomic reactivity of chloroacetamide 3 relative to acrylamide 14 and cyanoacrylamide 23, clear examples of cysteines were found that were preferentially liganded by the latter fragments ( FIG. 1F ). 
     In some instances, these findings demonstrate that the isoTOP-ABPP platform is one method for use to competitively profile fragment electrophiles against thousands of cysteine residues in native proteomes. 
     Cysteines Targeted by Fragment Electrophiles in Native Proteomes 
     Across all isoTOP-ABPP data sets combined, 758 liganded cysteines were identified on 637 distinct proteins, which corresponded to ˜12 and 22% of the total quantified cysteines and proteins, respectively ( FIG. 5A  and Tables 1-3). Only a modest fraction of the proteins harboring liganded cysteines were found in the DrugBank database (15%;  FIG. 5B ), indicating the fragment electrophiles targeted many proteins that lack small-molecule probes. Among protein targets with known covalent ligands, the fragment electrophiles frequently targeted the same cysteine residues as these known ligands (Table 4); examples include the protein kinase BTK, in which electrophilic fragments targeted an active-site cysteine that also reacts with the cancer drug ibrutinib, and XPO1 and ERCC3, in which electrophilic fragments targeted conserved cysteines that are modified by bioactive natural products and candidate anti-cancer agents. In the case of BTK, it was confirmed that the interaction of ibrutinib with this kinase was detected by isoTOP-ABPP, which also identified a known ibrutinib off-target—MAP2K7—in Ramos cell lysates ( FIG. 7A ). 
     DrugBank proteins with liganded cysteines mostly originated from classes that are regarded as “druggable”, including enzymes, channels, and transporters ( FIG. 5C ). Non-DrugBank proteins with liganded cysteines, on the other hand, showed a broader class distribution that included proteins, such as transcription factors and adaptor/scaffolding proteins, that are considered challenging to target with small-molecule ligands ( FIG. 5C ). Even among the enzymes targeted by fragment electrophiles, many examples were noted where the liganded cysteine was a non-active site residue ( FIG. 7B ). These data indicated that the cysteines modified by fragment electrophiles were not restricted to classical ligand-binding pockets on proteins. Also consistent with this premise, only ˜6% of all of the liganded cysteines were functionally annotated as active-site residues ( FIG. 5D ). Active-site cysteines, as well as redox-active cysteines, were still, however, substantially enriched among the liganded cysteine group compared to unliganded cysteines quantified by isoTOP-ABPP ( FIG. 5D ). It had been previously found that active-site and redox-active cysteines also show, in general, greater intrinsic reactivity (as measured with the IA-alkyne probe) compared to other cysteines. While this heightened reactivity is a likely contributory factor to the ligandability of cysteines, as reflected in the high proportion of hyperreactive cysteines that were detected as targets of fragment electrophiles ( FIG. 5E ), liganded cysteines were also well-represented across a broad range of intrinsic reactivities ( FIG. 5E ). Finally, most proteins were found to harbor a single liganded cysteine among the several cysteines that were, on average, quantified per protein by isoTOP-ABPP ( FIG. 5F ). The nuclear export factor XPO1 and metabolic enzyme PHGDH provide compelling examples of the selectivity displayed by fragment electrophiles for individual cysteines within proteins ( FIG. 5G  and  FIG. 7C ). Among the six different XPO1 cysteine residues quantified by isoTOP-ABPP, a single cysteine, C528, was frequently targeted by fragment electrophiles ( FIG. 5G ), and this residue is also modified by electrophilic drugs in clinical development for cancer 40 . Similarly, among eight quantified cysteines in PHGDH, only C369, a non-active site residue, was targeted by electrophilic fragments ( FIG. 7C ). 
     Liganded cysteines displayed strikingly distinct SARs with the fragment electrophile library ( FIG. 6A  and Tables 1-3). While a handful of cysteines were targeted by a large number of fragments (&gt;50%), most cysteines exhibited more restricted reactivity ( FIG. 6A , B and Tables 1-3). The operational grouping of fragment electrophiles based on their relative proteomic reactivity values (group A, &gt;10%; group B, &lt;10%) revealed SAR features that emphasized both the recognition and reactivity components of cysteine-electrophile interactions. Certain cysteines, for instance, preferentially interacted with the less reactive (group B) fragments (e.g., GLRX5; MSTO1; SRP9; UCHL3;  FIG. 6A ), while others were mainly liganded by the most reactive (group A) fragments (e.g., ATXN7L3B; CRKL; C2ORF49;  FIG. 6A ), although, even in these cases, the interactions differed substantially across group A fragments. Liganded cysteines located in the active sites of proteins tended to show broader reactivity with the fragment electrophiles compared to other cysteines ( FIG. 6C ), possibly reflecting their greater ligandability, but clear SARs were observed for many non-active site cysteines and these residues were not disproportionately targeted by group A fragments ( FIG. 6D ). These principles applied across different protein classes and were well-exemplified in kinases, for which &gt;20 liganded cysteines were identified that distributed near-evenly between active- and non-active-site residues ( FIG. 7D-F ). Even cysteines found in proteins considered challenging to drug, such as transcription factors/regulators, showed distinct SARs indicative of specific interactions involving both binding and reactivity ( FIG. 6D  and  FIG. 9G ). In addition, about greater than 60% of liganded cysteines, electrophile (IA-alkyne or fragment) reactivity was blocked by heat denaturation of the proteome, while about a fraction of unliganded cysteines (about 20%) showed decreased IA-alkyne labeling following heat denaturation ( FIGS. 15 and 16 ). In some instances, these results showed that the ligand-cysteine interactions are specific in that they depend on both the binding groups of ligands and structured sites in protein. 
     The availability of three-dimensional structures for a subset of proteins with liganded cysteines provided an opportunity to test whether docking predicts sites of fragment electrophile reactivity. Covalent docking programs have recently been introduced to discover ligands that target pre-specified cysteines in proteins; here, however, the aim was to computationally assess the relative ligandability of all cysteines within a protein and match these outputs to the data acquired in isoTOP-ABPP experiments. First, 29 representative protein targets were scanned and 99 solvent-accessible cysteines were identified. Then, the fragment electrophile library was docked on each residue independently using a modified potential to simulate non-covalent interactions preceding the alkylation event. In cases where the fragment electrophile bound favorably near a cysteine and the reactive group was within covalent bond distance of the cysteine, the cysteine was considered to be modified by the fragment. Docking scores were then calculated based on the estimated interaction energy of each fragment in its docked pose, and the ranking of these predictions matched the experimental data in 19 out of the 29 systems (i.e., cases where the top predicted ligandable cysteine matched the liganded cysteine determined by isoTOP-ABPP) ( FIG. 6E , F and Table 5). In six out of the remaining 10 systems, the liganded cysteines were ranked second by reactive docking. In the remaining four systems, reactive docking failed to predict the liganded cysteine due to limitations in the docking scoring function or structural issues in the models used. Notably, across the entire 29 proteins evaluated by reactive docking, it was found that cysteines predicted to be ligandable were much more likely to have been detected by isoTOP-ABPP compared to cysteines not predicted to be ligandable ( FIG. 6E  and  FIG. 7H ). It was also found that cysteines predicted to be ligandable were more likely to have been detected by isoTOP-ABPP and exhibited heat-sensitive IA-alkyne reactivity ( FIG. 17A  and  FIG. 17B ). These results indicate that reactive docking provides a good overall prediction of the ligandability of proteinaceous cysteines and suggest that IA-alkyne reactivity itself provides an independent experimental parameter useful for designating potentially ligandable cysteines in proteins. 
     Functional Analysis of Ligand-Cysteines Interactions 
     The next step was to confirm and determine the functional impact of ligand-cysteine interactions mapped by isoTOP-ABPP using recombinant proteins. Two proteins were selected for which the functional significance of the liganded cysteines had been previously demonstrated. The protein methyltransferase PRMT1 possesses a non-catalytic active-site cysteine (C109) that, when modified by electrophilic small molecules like 4-hydroxynonenal (HNE), results in the inhibition of PRMT1 activity 27 . Competitive isoTOP-ABPP revealed a very selective SAR for ligand engagement of C109 of PRMT1, with only three fragments (2, 11, and 51) blocking IA-alkyne labeling of this residue ( FIG. 6A  and  FIG. 8A  and Tables 1-3). Even though several additional cysteines in PRMT1 were quantified in isoTOP-ABPP experiments (none of which showed sensitivity to the tested fragment electrophiles;  FIG. 8A  and Tables 1-3), it was found that IA-rhodamine labeling of recombinant PRMT1 was blocked by mutating C109 to serine ( FIG. 8B ). These data are consistent with past studies indicating that C109 is the most reactive cysteine in PRMT1 and is selectively labeled by low concentrations of electrophilic probes. Using a convenient SDS-PAGE readout, it was confirmed that fragment 11 blocked IA-rhodamine labeling of PRMT1 with an IC 50  value of 36 μM, whereas control fragment 3 was inactive ( FIG. 8B , C), despite displaying similar overall proteome reactivity to 11 ( FIG. 4B ). Pre-treatment with 11, but not 3, also inhibited PRMT1-catalyzed methylation of histone 4 in a C109-dependent manner ( FIG. 8D ). These data indicate that electrophilic ligands targeting C109 act as PRMT1 inhibitors. 
     MLTK, or ZAK, which is a MAP3 kinase that possesses an active site-proximal cysteine residue C22 that is modified by HNE to feedback-inhibit JNK pathways under conditions of oxidative stress, was then examined. MLTK has also recently been implicated as an oncogenic driver in gastric cancer and is an off-target for ibrutinib, which reacts with C22 of MLTK. Competitive isoTOP-ABPP experiments identified a subset of fragment electrophiles that blocked IA-alkyne labeling of C22 in MLTK ( FIG. 9A  and Tables 1-3). The SAR provided by isoTOP-ABPP was verified and extended by testing fragments for blockade of labeling of recombinant MLTK using an ibrutinib-derived activity probe ( FIG. 8E  and  FIG. 9B ), which identified the benzofuran fragment 60 as having good potency for inhibiting MLTK (IC 50  value of 2.6 μM) and 3 as an inactive control probe ( FIG. 8E , F and  FIG. 9A , B). Fragment 60, but not 3, also blocked the catalytic activity of MLTK using a substrate phosphorylation assay, and this inhibitory effect was not observed with a C22A-MLTK mutant ( FIG. 8G  and  FIG. 18 ). 
     Next, proteins were evaluated that possessed previously uncharacterized liganded cysteines. IMPDH2, which is the rate-limiting enzyme in de novo synthesis of guanine nucleotides and regulates immune cell proliferation and cancer, contained two liganded cysteines—C140 and C331—that showed overlapping, but distinct SARs in competitive isoTOP-ABPP experiments ( FIG. 9C , D;  FIG. 19  and Tables 1-3). C331 serves as a catalytic nucleophile and active site-directed inhibitors of IMPDH2 have been described. C140, on the other hand, is found in a separate Bateman domain of IMPDH2, which serves as a module for allosteric regulation by sensing nucleotides ( FIG. 9D ) and has not been shown to react with electrophilic small molecules. Therefore focused was placed on the characterization of C140. It was first confirmed that fragment 14 directly labeled C140 of recombinant IMPDH2 by MS methods (Table 6). An alkyne analogue of 14 (18:  FIG. 8H ) was then synthesized, which provided a means to directly monitor ligand interactions at C140 by click chemistry conjugation to a rhodamine-azide tag and SDS-PAGE analysis. Click probe 18 labeled WT-IMPDH2 and a C331S-IMPDH2 mutant, but not the C140S or C140S/C331S mutants of this enzyme ( FIG. 8H ). Using this assay, it was confirmed that 14, but not control fragment 8, inhibited the labeling of IMPDH2 by 18 ( FIG. 9E ). IMPDH2 labeling by 18 was also inhibited by nucleotides ATP, AMP, and GTP, but not UTP or IMP ( FIG. 8I  and  FIG. 9F ). ATP blocked 18 labeling of IMPDH2 with an IC 50  value of 45 μM ( FIG. 8J ). Thus, covalent ligands targeting the Bateman domain of IMPDH2 serves not only as inhibitors, but also probes of nucleotide binding to this enzyme. 
     Two liganded cysteines—C114 and C161—were also identified in the p53-induced phosphatase TIGAR ( FIG. 9G , H). In some instances, TIGAR acts as both a fructose-2,6-bisphosphatase and 2,3-bisphosphoglycerate phosphatase to shape the metabolic state of cancer cells and protect them from ROS-induced apoptosis. Inhibitors of TIGAR have not been described. C114 is found on the lid of the TIGAR active site, ˜15 Å from the phosphate substrate binding site ( FIG. 9H ). C161 resides on the opposite side of the protein. Focus was placed on the characterization of fragment labeling of C114 given its proximity to the TIGAR active site. It was first confirmed that both C114 and C161 of recombinant TIGAR were labeled by the IA-rhodamine probe and this labeling was partly diminished in C114S and C161S single mutants and fully blocked in a C114S/C116S double mutant of TIGAR ( FIG. 9I ). It was also verified interactions of hit fragment 5 with C114 of TIGAR by LC-MS analysis (Table 6) and by showing that the fragment blocked IA-rhodamine labeling of a C161 S-TIGAR mutant with an IC 50  value of 16 μM ( FIG. 8K , L); in contrast, the control fragment 3 showed much lower potency ( FIG. 8K , L), 5 also blocked the catalytic activity of WT- and C161S-, but not C114S- or C114S/C161 S-TIGAR using a substrate assay ( FIG. 8M ). Control fragment 3 did not affect TIGAR catalytic activity ( FIG. 8L ). Inhibition of TIGAR substrate turnover by 5 plateaued at 70% ( FIG. 9J ), which indicates that the covalent ligand acts by an allosteric mechanism or does not extend fully into the active site of TIGAR to produce complete inhibition. 
     Electrophilic Ligands that Inhibit IDH1 Activity in Cancer Cells 
     Isocitrate dehydrogenase 1 (IDH1) and 2 (IDH2) are mutated in a number of human cancers to produce enzyme variants with a neomorphic catalytic activity that converts isocitrate to 2-hydroxyglutarate (2-HG). Increases in 2-HG inhibit α-ketoglutarate-dependent dioxygenases that function as tumor suppressors, in particular, by methylating DNA and proteins. Competitive isoTOP-ABPP experiments identified distinct subsets of ligands that targeted a conserved cysteine in IDH1 and IDH2 (C269 and C308, respectively; Tables 1-3). This cysteine is an active site-proximal residue that is 13 Å from the NADP +  molecule in a crystal structure of IDH1 ( FIG. 10A ); glutathionylation of C308 has previously been shown to block IDH2 activity, but, to our knowledge, irreversible inhibitors of IDH enzymes have not been characterized. 
     The functional significance of ligand interactions with IDH enzymes by recombinantly expressing wild type (WT) and a C269S mutant of IDH1 was explored. WT-, but not C269S-IDH1 reacted with the IA-rhodamine probe as detected by SDS-PAGE, and fragment electrophiles blocked this reaction with an SAR that mirrored that observed for endogenous IDH1 in competitive isoTOP-ABPP experiments ( FIG. 11A  and Tables 1-3). Fragment 20 inhibited IA-rhodamine labeling of WT-IDH1 with an IC 50  value of 2.9 μM ( FIG. 11B  and  FIG. 10B ) and showed similar activity with the R132H oncogenic mutant of IDH1 ( FIG. 10C  and  FIG. 20 ). It was also confirmed by isoTOP-ABPP that 20 (25 μM) completely blocked IA-alkyne labeling of endogenous IDH1 in MDA-MD-231 proteomes (R value=20;  FIG. 10D ) and, by MS analysis, that 20 directly modifies C269 of IDH1 (Table 6). Fragment 2 showed much less activity against C269 of IDH1 (IC 50 &gt;50 μM;  FIG. 11B  and  FIG. 10B ) and was therefore selected as a control probe. It was found that 20 blocked in a concentration-dependent manner the catalytic activity of WT-IDH1 (as measured by the reduction of NADP +  to NADPH in the presence of isocitrate), but did not inhibit the activity of the C269S-IDH1 mutant ( FIG. 11C ). The in situ activity of 20 was also tested by generating a human cancer cell line that stably overexpressed R132H-IDH1 ( FIG. 10E ). The R132H-IDH1 cells were treated with fragments 20 and 2 for 2 h, lysed, and assayed ex situ for 2-HG production, 20 (50 μM) near-completely blocked 2-HG production by R132H cell lysates, while 2 (50 μM) only caused a slight decrease in this activity ( FIG. 11D ). Parallel competitive isoTOP-ABPP experiments confirmed that fragment 20, but not fragment 2 inhibited IA-alkyne labeling of C269 of IDH1 in situ ( FIG. 10F ). 
     Global Profiling of Cysteine-Reactive Fragments in Cells 
     Encouraged by the cellular activity of the IDH1 ligand 20, the capacity of fragment electrophiles to modify proteinaceous cysteines in situ was more broadly assessed. MDA-MB-231 and Ramos cells were treated with representative members of the fragment library (23 compounds tested in total; each compound tested at 200 μM, 2 h in situ treatment), and the cells were then harvested, lysed, and analyzed by isoTOP-ABPP. A handful of fragments were cytotoxic to cells and re-tested at lower (50 or 100 μM) concentrations. The tested fragments showed a broad range of in situ reactivities that generally matched their respective reactivities in vitro ( FIG. 11E  and Tables 1-3). Some fragments, however, showed somewhat greater reactivity in cells, while fragment 11 was notably devoid of activity in situ ( FIG. 11E ). These differences reflect the impact of transport and/or metabolic pathways on the cellular concentrations of fragment electrophiles. A substantial fraction (64%) of the liganded cysteines identified in cell lysates were also sensitive to the same electrophilic fragments in cells ( FIG. 11F ). A handful of fragment-cysteine interactions were also observed selectively in situ, but not in lysates, including C182 of p53 (TP53), a redox-regulated residue at the dimerization interface of the DNA binding domain 50  ( FIG. 11G ). In some instances, these liganded cysteines require an intact cellular environment to preserve their interactions with fragment electrophiles. Taken together, these findings indicate that the ligandability of cysteine residues is generally similar in lysates and cells, although exceptional cases underscore the importance of having the capability to perform ligand discovery experiments in situ. 
     Electrophilic Ligands that Target Pro-Caspase-8 and Block Extrinsic Apoptosis 
     Several fragments targeted the catalytic cysteine nucleophile C360 of the protease caspase-8 (CASP8) in isoTOP-ABPP experiments performed in vitro and in situ ( FIG. 12A  and Tables 1-3). CASP8 plays important roles apoptosis, immune cell proliferation, and embryonic development, but selective, non-peptidic, and cell-active inhibitors for this protease are lacking. Representative fragment hits against recombinant, active CASP8 were screened using substrate and activity-based probe (Rho-DEVD-AOMK probe (“DEVD” disclosed as SEQ ID NO: 857)) assays and observed marginal to no inhibition with most fragments ( FIG. 12B ). Initially puzzled by this outcome, it was hypothesized that fragment labeling of CASP8 in isoTOP-ABPP experiments might reflect reaction with the inactive zymogen (pro-) rather than active form of this protease. Western blots confirmed that most, if not all of the CASP8 in MDA-MB-231 cell lysates existed in the pro-form ( FIG. 12C ). Next a recombinant form of pro-CASP8 was expressed with mutated cleavage sites (D374A and D384 Å) to prevent processing and activation. A non-catalytic cysteine C409S of pro-CASP8 was also mutated, which enabled detection of C360 labeling with IA-rhodamine by SDS-PAGE analysis ( FIG. 13A ). Several hit fragments detected in isoTOP-ABPP experiments completely blocked IA-rhodamine labeling of pro-CASP8 ( FIG. 12D ). Fragment 7 displayed the highest potency, with an IC 5 s value of ˜5 M ( FIG. 13A , B), which, when combined with the low overall proteome reactivity of this fragment (3%), designated it as suitable tool compound for further studies. 
     Fragment 7 (50 μM) fully blocked IA-alkyne labeling of C360 of CASP8 in isoTOP-ABPP experiments performed in both Ramos and Jurkat cell lysates ( FIG. 13C ). Next, a clickable analogue of 7 (61) was synthesized and it was found that this probe (25 μM) strongly labeled pro-CASP8, but not a C360S-pro-CASP8 mutant ( FIG. 13D  and  FIG. 12E ).  7  (50 μM) blocked labeling of pro-CASP8 by 61, but did not inhibit labeling of active CASP8 by the Rho-DEVD-AOMK probe (“DEVD” disclosed as SEQ ID NO: 857) developed to target active caspases ( FIG. 13D  and  FIG. 12F ). Conversely, the general caspase inhibitor Ac-DEVD-CHO (“DEVD” disclosed as SEQ ID NO: 857) (20 μM) blocked Rho-DEVD-AOMK (“DEVD” disclosed as SEQ ID NO: 857) labeling of active CASP8, but not 61 labeling of pro-CASP8 ( FIG. 13D ,  FIG. 12F , and  FIG. 21A ). Similar results were obtained in substrate assays, where DEVD-CHO (“DEVD” disclosed as SEQ ID NO: 857), but not 7, blocked CASP8 activity ( FIG. 13E ). Cross-reactivity of 7 with other caspases was not observed, including recombinant, active CASP3 assayed with a substrate ( FIG. 13E ) or the Rho-DEVD-AOMK probe (“DEVD” disclosed as SEQ ID NO: 857) ( FIG. 12F ) or CASP2 and CASP7 in cell lysates measured by isoTOP-ABPP ( FIG. 12G ). Finally, to further verify that 7 preferentially reacts with pro-CASP8 over active CASP8 in complex biological systems, recombinant forms of these proteins were doped into MDA-MB-231 cell lysates followed by treatment with 7 (30 μM, 1 h) or DMSO and analysis by isoTOP-ABPP, 7 produced a near-complete blockade of IA-alkyne labeling of C360 for pro-CASP8 (R=10), but had little effect on IA-alkyne reaction with C360 of active CASP8 (R=1.9) ( FIG. 13F ). 
     Treatment of Jurkat cell lysates with 10 or 100 μM of 61, followed by analysis of the combined samples by isoTOP-ABPP, confirmed direct labeling of C360 of CASP8 by 61 ( FIG. 12H ). The low R value observed for C360 in this analysis (R=2) indicated near complete labeling of this cysteine by 61 at 10 μM in cell lysates, consistent with the low μM IC 50  value displayed by the parent fragment 7 for inhibiting IA-rhodamine labeling of C360 of CASP8 ( FIG. 13B ). The effect of pro-CASP8 inhibition in cellular apoptosis assays was next to be evaluated. Because C360 is the catalytic nucleophile of CASP8, mutation of this residue was not possible to create a control protein for evaluating the pharmacological effects of 7 in cells. Instead, a structurally related inactive probe was developed for this purpose. It was found that bulky substituents placed on the aniline ring of 7 furnished compounds such as 62 that did not inhibit pro-CASP8 labeling by IA-rhodamine ( FIG. 13B , G). It was confirmed that 62 also did not inhibit active CASP3 or CASP8 using substrate ( FIG. 13E ) and activity-probe ( FIG. 12F ) assays and was inactive against endogenous CASP8, CASP2, or CASP7 in Jurkat lysates as determined by isoTOP-ABPP ( FIG. 12G ). Based on these data, 62 was designed as a suitable inactive control probe for studying the inhibition of pro-CASP8 by 7. Jurkat cells were treated with 7 or 62 (30 μM, 30 min) prior to addition of FASL or staurosporine (STS) to induce extrinsic and intrinsic apoptosis, respectively, 7, but not 62, completely blocked FASL-induced apoptosis ( FIG. 13H  and  FIG. 21B-C ), as well as the proteolytic processing of CASP3, CASP8, and the apoptosis marker PARP ( FIG. 13I ). In contrast, 7 did not block STS-induced intrinsic apoptosis ( FIG. 13H ) or the cleavage of PARP and CASP3, although the compound did substantially inhibit cleavage of CASP8 in these cells ( FIG. 13I ). The non-selective caspase inhibitor VAD-FMK prevented both FASL- and STS-induced apoptosis and associated proteolytic processing events ( FIG. 13H , I). Chemical proteomic experiments revealed that 7 fully inhibited CASP8, as well as the related initiator caspase CASP10 (but not other caspases, including CASP2, 3, 6, and 9) in Jurkat cells ( FIG. 14A  and  FIG. 22A ). It was confirmed that 7 blocked labeling of pro-CASP10 by 61 with an apparent IC50 value of 4.5 μM ( FIG. 22B-D ), but did not inhibit active CASP10 as measured by labeling with the Rho-DEVD-AOMK probe (“DEVD” disclosed as SEQ ID NO: 857) ( FIG. 21A ) or a substrate assay ( FIG. 22E ). As such, in some instances, 7 blocking CASP8 processing in both FASL- and STS-treated cells supports a model where CASP8 activation mainly occurs through auto-processing in either extrinsic or intrinsic apoptosis, but is only required for the former type of programmed cell death. 
     In some instances, the respective functions of CASP8 and CASP10 in extrinsic apoptosis and other cellular processes remain poorly understood in large part due to a lack of selective, non-peptidic, and cell-active inhibitors for these enzymes and the absence of animal models for CASP10 (which is not expressed in rodents). In some cases, the potency and selectivity of 7 was improved to address this issue. Conversion of the 4-piperidino moiety to a 3-piperidino group and addition of a p-morpholino substituent to the benzoyl ring of 7 furnished compound 63 that was separated by chiral chromatography into its two purified enantiomers, 63-R ( FIG. 4 c   ) and 63-S, the former of which showed substantially improved activity against CASP8 (apparent IC 50  value of 0.7 μM (95% CI, 0.5-0.8);  FIG. 22F-H ) and negligible cross-reactivity with CASP10 (IC 50  value&gt;100 μM;  FIG. 22C , D, F), 63-S was much less active against CASP8 (apparent IC 50  value of 15 μM,  FIG. 22G , H) and also inactive against CASP10 ( FIG. 14A ). With dual CASP8/10 (7) and CASP8-selective (63-R) ligands in hand, we next set out to investigate the biological functions of these proteases. 
     The effects of caspase ligands in human T cells were evaluated, where both CASP8 and CASP10 are highly expressed ( FIG. 22I ) in Jurkat cells, which are a commonly studied immortalized human T cell line. It was found that 63-R fully blocked FasL-induced apoptosis in Jurkat cells and did so with greater potency than 7 ( FIG. 14B  and  FIG. 22J ) or 63-S ( FIG. 22K ). Similar results were obtained in HeLa cells, which express CASP8, but not CASP1026 ( FIG. 22L ). In contrast to these cell line results, FasL-induced apoptosis in primary human T cells showed substantial resistance to 63-R at all tested concentrations and instead was completely inhibited by the dual CASP8/10 ligand 7 ( FIG. 14B ). It was confirmed by chemical proteomics with probe 61 that 7 blocked both CASP8 and CASP10, while 63-R inhibited CASP8, but not CASP10, in primary human T cells and Jurkat cells ( FIG. 14A ). Consistent with these cell death results, 7, but not 63-R, prevented proteolytic processing of CASP3 and CASP10 in primary human T cells ( FIG. 22M ). In some instances, the processing of both CASP8 and the initiator caspase substrate RIP kinase were also preferentially inhibited by 7 versus 63-R ( FIG. 22M , indicating that CASP10 also contribute to these proteolytic events in T cells, as has been suggested by biochemical studies. 
     Example 2 
     Dimethyl fumarate (DMF) is a drug used to treat autoimmune conditions, including multiple sclerosis and psoriasis. In some instances, the mechanism of action of DMF is unclear, but is proposed to involve covalent modification of proteins and/or serving as a pro-drug that is converted to monomethyl fumarate (MMF). Using an isoTOP-ABPP approach, the mechanism of action of DMF is examined. 
     Chemical Reagents 
     Assays were performed with the following reagents: dimethyl fumarate (DMF; 242926; Sigma Aldrich), monomethyl fumarate (MMF; 651419; Sigma Aldrich), dimethyl succinate (DMS: W239607; Sigma Aldrich), and buthionine sulfoximine (BSO; 14484; Cayman Chemical). 
     Isolation of Primary Human T Cells 
     All studies using samples from human volunteers follow protocols approved by the TSRI institutional review board. Blood from healthy donors (females aged 30-49) were obtained after informed consent. Peripheral blood mononuclear cells (PBMCs) were purified over Histopaque-1077 gradients (10771; Sigma) following the manufacturer&#39;s instructions. Briefly, blood (20×25 mL blood aliquots) were layered over Histopaque-1077 (12.5 mL) and the samples were then fractionated by centrifugation (2000 rpm, 20 min, 20° C., no brake). PBMC&#39;s were harvested from the Histopaque-plasma interface and washed twice with PBS. After that time, the T cells were isolated using an EasySep™ Human T Cell Isolation Kit (17951; STEMCELL) per the manufacturer&#39;s instructions. 
     Mice 
     C57BL/6J and Nrf2′ mice (Stock No:017009; Nfe212 tm1Ywk ; Jackson Labs) were bred and maintained in a closed breeding facility at The Scripps Research Institute and were 6-8 weeks old when used in experiments. All mice were used in accordance with guidelines from the Institutional Animal Care and Use Committee of The Scripps Research Institute. 
     For the PKCθ studies, C57BL/6 mice and Prkcq−/− mice were housed under specific pathogen-free conditions and used in accordance with a protocol approved by the La Jolla Institute for Allergy and Immunology Animal Care Committee. 
     Isolation of Primary Mouse T Cells 
     Spleens were harvested from female mice, perfused with collagenase, and incubated at 37° C. with 5% CO 2  for 30 min. After this time, the spleens were homogenized. Cells that passed through a 100 mun cell strainer were collected and washed with RPMI. T cells were isolated from the splenocytes using the EasySep™ Mouse T cell Isolation Kit (19851; STEMCELL) according to manufacturer&#39;s instructions. 
     For the PKCθ studies, CD4′ T cells were isolated by anti-mouse CD4 magnetic particles (L3T4; BD IMag) and were cultured in RPMI-1640 medium (Gibco) supplemented with 10% (vol/vol) heat-inactivated FBS, 2 mM glutamine, 1 mM sodium pyruvate, 1 mM MEM nonessential amino acids, 100 U/mL each of penicillin G and streptomycin (Life Technologies) and recombinant IL-2 (100 U/mL, Biolegend). 
     T Cell Stimulation 
     96-well plates were coated with anti-CD3 (1:200; BioXcell) and anti-CD28 (1:500; 302933; BioLegend) in PBS (100 μL/well) overnight at 4° C. The plates were then washed twice with PBS and to each well was added 500,000 primary T cells in 100 μL of RPMI supplemented with 10% FBS, glutamine, and Pen-Strep. Cells were then treated with 100 μL of media containing compound at the indicated concentrations (final well volume of 200 μL). Cells were left at 37° C. in a 5% CO 2  incubator for the indicated periods of time and harvested by centrifugation (500 g, 8 min, 4° C.), followed by washing with PBS. 
     Cellular Analysis and Sorting by Flow Cytometry 
     Cells were transferred to a round bottom 96-well plate (0720095; Fisher Scientific), harvested by centrifugation (500 g, 3 min, 4° C.), washed with PBS, and stained with LIVE/DEAD fixable cell stain (L23105; ThermoFisher) according to the manufacturer&#39;s instructions. Briefly, one vial of LIVE/DEAD stain was resuspended in 50 uL of DMSO and added to 20 mL of PBS. To each well of the 96-well plate was added 200 μL of the stain, and the cells were incubated on ice for 30 min in the dark. After this time, cells were pelleted and washed once with PBS, then stained for cell surface antigens. 
     Flow cytometry analysis of cell surface antigens was performed with the following antibodies: Pacific Blue-conjugated anti-CD8 (1:25 dilution; clone RPA-T8; BD Biosciences), APC-conjugated anti-CD4 (1:25 dilution; clone RPA-T4; eBioscience), phycoerythrin-conjugated anti-CD25 (1:25 dilution; clone BC96; eBioscience or PC61; BioLegend (PKCθ studies)), FITC-conjugated anti-CD69 (1:25 dilution; clone FN50; eBioscience). All antibodies were diluted in 1% FBS in PBS, and 50 μL of the stain solution was added to each well. Cells were stained for 15 min on ice in the dark, after which cells were harvested by centrifugation (500 g, 3 min, 4° C.), washed with 1% FBS in PBS, and resuspended in 200 μL/well of 4% PFA in PBS. Flow cytometrv acquisition was performed with BD FACSDiva™-driven BD™ LSR II flow cytometer (Becton, Dickinson and Company). Data was then analyzed with FlowJo software (Treestar Inc.). Data represent mean±SE for four-five experiments per group. 
     Quantification of Secreted Cytokines by Enzyme-Linked Immunosorbent Assay (ELISA) 
     T cells were harvested and stimulated as described above. At the indicated time points, cell culture supernatants were collected and IL-2 levels were measured in clear microplates (991427; R&amp;D Systems) according to the manufacturer&#39;s instructions (Human IL-2 DuoSet ELISA; DY202; R&amp;D Systems). Plates were read in a Gemini SpectraMax 250 microplate reader set to 450 nm. Data represent mean±SE for four experiments per group. 
     For the PKCθ studies, aliquots of transduced Prkcq −/−CD4+ T cells  (1×10 6 ) were stimulated for 48 h with anti-CD3 alone or anti-CD3 plus anti-CD28, and the concentration of IL-2 in culture supernatants was determined by enzyme-linked immunosorbent assay according to the manufacturer&#39;s instructions (BioLegend). Briefly, a 96-well plate (Corning Costar) was coated overnight at 4° C. with mAb to IL-2. Triplicates of IL-2 standards and supernatants from cultured cells were then added to the plate, followed by 2h incubation at room temperature. A biotinylated polyclonal antibody to IL-2 was added to the plate, followed by incubation for 1 h at room temperature, and then Avidin-HRP was added, followed by incubation for 30 min at room temperature. The amount of bound avidin was then assessed with TMB peroxidase that was acidified by 2 N H 2 SO 4 . The absorbance of each well at 450 nm was then measured with a spectrophotometric plate reader (BioTek). 
     Quantification of Cellular Glutathione (GSH) Levels 
     Primary human T cells (2.5 million cells/mL, 20 mL per condition) were treated as indicated, harvested by centrifugation (500 g, 8 min, 4° C.), and washed twice with PBS. To the cell pellet was added 75 μL of lysis buffer. After vortexing, the samples were incubated on ice for 15 min, then harvested by centrifugation (16,000 g, 10 min, 4° C.). Protein concentrations were adjusted to at least 5 mg/mL and the assay performed according to manufacturer&#39;s instructions (Sigma-Aldrich, CS1020). Data represent mean±SE for two biological replicates. 
     Protein Labeling and Click Chemistry 
     Cells were lysed by sonication and diluted to a concentration of 2 mg protein/mL. Protein concentrations were measured with the Bio-Rad DC™ protein assay reagents A and B (5000113, 5000114; Bio-Rad). 500 μL of proteome sample was treated with 100 μM of IA-alkyne probe using 10 μL of a 10 mM DMSO stock. The labeling reactions were incubated at room temperature for 1 h upon which time the samples were conjugated to isotopically-labeled TEV-cleavable tags (TEV tags) by copper-catalyzed azide-alkyne cycloaddition (CuACC or ‘click chemistry’). 60 μL of heavy click chemistry reaction mixture was added to the DMSO-treated control sample and 60 μL of the light reaction mixture was added to the compound-treated sample. The click reaction mixture comprised TEV tags (10 μL of a 5 mM stock, light (fragment treated) or heavy (DMSO treated)), CuSO 4  (10 μL of a 50 mM stock in water), and TBTA (30 μL of a 1.7 mM stock in 4:1 tBuOH:DMSO). To this was added TCEP (10 μL of a 50 mM stock). The reaction was performed for 1 h at room temperature. 
     The light- and heavy-labeled samples were then centrifuged (16.000 g, 5 min, 4° C.) to harvest the precipitated proteins. The resulting pellets were resuspended in 500 μL of cold methanol by sonication and the heavy and light samples combined pairwise. Combined pellets were then washed with cold MeOH, after which the pellet was solubilized in PBS containing 1.2% SDS by sonication. The samples were heated at 90° C. for 5 min and subjected to streptavidin enrichment of probe-labeled proteins, sequential on-bead trypsin and TEV digestion, and liquid chromatography-tandem mass spectrometry (LC-MS/MS) according to the published isoTOP-ABPP protocols. 
     Peptide and Protein Identification 
     RAW Xtractor (version 1.9.9.2) was used to extract the MS2 spectra data from the raw files. MS2 data were searched against a reverse concatenated, nonredundant variant of the Human UniProt database (release-2012_11) using the ProLuCID algorithm. Cysteine residues were searched with a static modification for carboxyamidomethylation (+57.02146) and up to one differential modification for either the light or heavy TEV tags (+464.28595 or +470.29976, respectively). Peptides were required to have at least one tryptic terminus and to contain the TEV modification. ProLuCID data was filtered through DTASelect (version 2.0) to achieve a peptide false-positive rate below 1%. 
     R Value Calculation and Processing 
     The quantification of heavy/light ratios (isoTOP-ABPP ratios, R values) was performed by in-house CIMAGE software using default parameters (3 MS1&#39;s per peak and signal to noise threshold of 2.5). Site-specific engagement of electrophilic compounds was assessed by blockade of IA-alkyne probe labeling. For peptides that showed a=95% reduction in MS1 peak area from the compound-treated proteome (light TEV tag) when compared to the DMSO treated proteome (heavy TEV tag), a maximal ratio of 20 was assigned. Overlapping peptides with the same labeled cysteine (for example, same local sequence around the labeled cysteines but different charge states, MudPIT segment numbers, or tryptic termini) were grouped together, and the median ratio from each group was recorded as the R value of the peptide for that run. 
     Analysis of Cysteine Conservation 
     For each human protein containing a DMF-sensitive cysteine, the mouse homolog was identified and the human and mouse sequences aligned using the Align tool on UniProt. 
     Immunofluorescent Analysis of NF-kB Translocation 
     Primary human T cells were harvested and stimulated as described above (500,000 cells/well), with concomitant treatment with DMSO or DMF for 60 min. Cells were pelleted (500 g, 3 min, 4° C.), then each well was resuspended in 50 μL PBS and added to Poly-D-lysine coated covcrslips (12 mm; 354087; Corning® BioCoat™). Cells were allowed to adhere to the coverslips for 30-60 min at 4° C. Coverslips were transferred to a 6 well plate and fixed with 4% PFA (157-4-100; Electron Microscopy Sciences) at room temperature for 10 min. After washing three times with PBS, cells were permeabilized with 0.1% Triton X-100 in PBS at room temperature for 10 min. Cells were washed three times with PBS, then placed cell-side-up on Parafilm. To each cover slip was added 150 μL of blocking buffer (2% BSA in PBS), and the slides were blocked for 30 min at room temperature. 
     The blocking buffer was aspirated, coverslips placed face down in 40 μL of antibody buffer (anti-human p65; p65Ab; FivePhoton Biochemicals; 1:500 dilution in blocking buffer), and allowed to stain overnight at 4° C. in a wet chamber. Cover slips were washed three times with PBS, then incubated with 150 μL of secondary antibody (anti-rabbit Alexa Fluor 488; A21441; Life Technologies; 1:200 dilution in PBS) for 2 h at room temperature. After washing three times with PBS, 150 μL of Hoechst counter stain was added (5 μg/mL in PBS) and coverslips were left at room temperature for 30-60 min. Cells were again washed with PBS three times, then stained with Alexa Fluor 555 Phalloidin red (8953S; Cell Signaling; 1:20 dilution in PBS). The coverslips were washed with PBS a final three times, then transferred to SuperFrost Plus slides (12-550-15, Fisherbrand) spotted with 10 μL of Prolong, Gold Antifade Mountant (P36934. ThermoFisher). The circumference of each coverslip was sealed with clear nail polish (72180; Electron Microscopy Sciences). 
     Images were acquired using a Zeiss 780 laser scanning confocal microscope with a 63× Objective (0.3 um image step size) and the automated stitching module to merged (10% overlap) and create a three dimensional multi-paneled mega image composite. The composite image was gathered as a z-series of at least 9 individual image panels that were auto-merged using zen software. The mega-image composite was projected into a maximum image projection in the zen software then analyzed using the colocalization modual in Zen (Zeiss Inc) and Image Pro Premier (Media Cybernetics). The Mander&#39;s Correlation Coefficients (MCC), specifically M1 and M2 between the various combination of fluorescent label (Rhodamine Phalloidin vs NFkB-P65 and Hoechst vs NFkB-p65) are calculated in ZEN (Zeiss inc) per cell and displayed as a percent. Each cell was outlined using the region of interest module and the software then calculated the M1 and M2 correlation coefficients between the two fluorophores and tabulated the results. The fluorescent signal dynamic range and threshold cutoffof real signal was defined by multiple background and secondary controls. Correlation coefficient values were compared using Image Pro Premier (IPP) (Media Cybernetics), where images were imported as raw calibrated czi files and analyzed using a similar module in IPP. Similar results were obtained with both platforms (not shown). Data represent mean±SE for two-three biological replicates. 
     Subcloning and Mutagenesis 
     QuikChange site-directed mutagenesis was performed on a pEF4 His A plasmid containing the full length human PKCθ (residues 1-707). The PKCθ insert was excised using BamHI and Xhol, then ligated into a pMIG vector. 
     PKCθ Retroviral Transduction and Stimulation 
     Platinum-E packaging cells were plated in a six-well plate in 2 mL RPMI-1640 medium plus 10% FBS. After 24 h, cells were transfected with empty pMIG vector or the appropriate PKCθ-expressing vector DNA (3 μg) with TranslT-LTI transfection reagent (Mirns Bio). After overnight incubation, the medium was replaced and cultures were maintained for another 24 h. Retroviral supernatants were then collected and filtered, supplemented with 8 μg/mL of polybrene and used to infect CD4 +  T cells that had been pre-activated for 24 h with plate-bound monoclonal antibody to CD3 (8 μg/mL) and CD28 (8 μg/mL). After centrifuging plates for 1.5-2 h at 2,000 r.p.m., cell supernatants were replaced by fresh RPMI-1640 supplemented with 10% FBS and recombinant IL-2 (100 U/mL). Cells were incubated for another 24h at 37° C. On day 3, cells were washed, moved to new plates and cultured in RPMI-1640 medium containing 10% FBS and recombinant IL-2 (100 U/mL) without stimulation for 2 additional days before restimulation with mAb to CD3 alone or plus mAb to CD28. 
     PKCθ Immunoprecipitation and Immunoblot Analysis 
     Cells were lysed in 1% (wt/vol) digitonin (D141, Sigma) lysis buffer (20 mM Tris-HCl. pH7.5, 150 mM NaCl, 5 mM EDTA) supplemented with protease inhibitors (10 μg/mL aprotinin, 10 μg/mL leupeptin and 1 mM PMSF) and phosphatase inhibitors (5 mM sodium pyrophosphate and 1 mM Na 3 VO 4 ). Supernatants were incubated 2h with 1 μg anti-CD28 mAb, and proteins were immunoprecipitated overnight at 4° C. with protein G-Sepharose beads (GE Healthcare). The immunoprecipitated proteins were resolved by SDS-PAGE, transferred onto a PVDF membrane and probed overnight at 4° C. with primary antibodies, followed by incubation for 1 h at room temperature with horseradish peroxidase (HRP)-conjugated secondary antibodies. Signals were visualized by enhanced chemiluminescence (ECL; GE Healthcare) and were exposed to X-ray film. Densitometry analysis was performed with ImageJ software. Immunoblotting antibodies to CD28 (C-20) and PKCθ (C-19) were obtained from Santa Cruz Biotechnology. 
     DMF, but not MMF, Inhibits T Cell Activation 
     Multiple sclerosis is an autoimmune disease with a prominent T cell component; as such, it was reasoned that DMF in some cases impact primary T cell activation. Consistent with this, previous reports have shown that DMF inhibits cytokine release from mouse splenocytes and promotes a Th2 phenotype via induction of IL-10-producing type II dendritic cells. The effects of DMF and MMF ( FIG. 23A ) were tested on cytokine release from primary human T cells activated with anti-CD3, anti-CD28 antibodies. Secretion of IL-2 was strongly inhibited by DMF, but not MMF ( FIG. 23B ). DMF, but not MMF or the non-electrophilic analogue dimethyl succinate (DMS,  FIG. 23A ) also blocked the expression of the early activation markers CD25 ( FIG. 23C , D) and CD69 ( FIG. 23E ) in anti-CD3, anti-CD28-stimulated T cells. The blockade of T cell activation by DMF was concentration-dependent, with 10, 25 and 50 μM of the drug producing marginal/negligible, partial, and near-complete inhibition, respectively ( FIG. 23B , D, E). In some instances, the effects of DMF on cytokine release and activation markers occurred at concentrations of the drug that did not impair T cell viability ( FIG. 24 ). Similar results were obtained with primary splenic T cells from C57BL/6 mice, the activation of which was also suppressed by DMF, but not MMF or DMS ( FIG. 25 ). Of note, the inhibitory effects of DMF were reduced if the drug was added two hours after anti-CD3, anti-CD28 stimulation and completely ablated if the drug was added six hours after stimulation ( FIG. 23F ), suggesting that DMF inhibits an early event(s) in the T cell activation pathway 
     DMF Effects on T Cell Activation are Independent of Nrf2 and GSH 
     DMF is thought to produce neuroprotective effects through activating the Nrf2-Keap1 pathway, but whether this pathway contributes to the immunomodulatory effects of DMF is unclear. A recent study showed that DMF inhibits pro-inflammatory cytokine release from primary mouse splenocytes and this effect was comparable in wild type and Nrf2(−/−) splenocytes (Gillard, et al., “DMF, but not other fumarates, inhibits NF-kappaB activity in vitro in an Nrf2-independent manner,”  J. Neuroimmunol.  283, 74-85 (2015)). Consistent with this, it was found that the activation of Nrf2(+/+) and (−/−) T cells was similarly sensitive to inhibition by DMF ( FIG. 26A ). In some instances, DMF also impair T cell activation through depleting glutathione (GSH), and, indeed, DMF-treated primary human T cells showed a significant decrease in cellular GSH content ( FIG. 26B ). Significant reductions in GSH were, however, also observed with the GSH synthesis inhibitor buthionine sulfoximine (BSO), which had no effect on T cell activation ( FIG. 26C , D). In some cases, these data indicate that the blockade of T cell activation by DMF involves processes other than Nrf2 activation or GSH depletion. 
     Chemical Proteomic Discovery of DMF-Sensitive Cys Residues in T Cells 
     The inhibition of T cell activation by DMF, but not the non-electrophilic analogues MMF and DMS, pointed to a mechanism that involves covalent reactivity with one or more proteins important for T cell function. As such, a globally inventory of DMF-sensitive Cys residues in primary human and mouse T cells were examined using the quantitative chemical proteomic platform isoTOP-ABPP. In this method, DMF is evaluated for its ability to block the reactivity of proteinaceous Cys residues with the general electrophilic probe iodoacetamide-alkyne (IA-alkyne). Using isotopically differentiated azide-biotin tags (containing a TEV protease-cleavable linker), Cys residues are identified and comparatively quantified for their IA-reactivity in cells treated with DMF versus DMSO control. Primary advantages of the isoTOP-ABPP platform include: 1) the competing electrophile does not itself need to be chemically altered for target identification, which is particularly beneficial when studying very small compounds like DMF; and 2) isotopic labeling occurs late in the sample processing, which facilitates the quantitative analysis of primary cells and tissues that are not readily amenable to metabolic labeling. 
     The isoTOP-ABPP method was performed on primary human T cells treated with DMSO or DMF (50 μM, 4 h). Five independent replicates were performed, and the total aggregate number of unique quantified peptides and proteins began to plateau by the fourth and fifth replicate ( FIG. 28 ), indicating that we approached maximal proteomic coverage of IA-reactive Cys residues in human T cells under the conditions employed. Of the more than 2400 quantified Cys residues, a small fraction (˜40) showed substantial reductions (&gt;four-fold; isoTOP-ABPP ratio (R value)&gt;4) in IA-alkyne labeling in DMF-treated T cells ( FIG. 27A , and Tables 7-9). Similar isoTOP-ABPP analyses revealed that none of the ˜40 DMF-sensitive Cys residues were altered by MMF (50 μM, 4 h) or BSO (2.5 mM, 4 h) treatment, which, in general, affected the reactivity of very few Cys residues across the T cell proteome ( FIG. 27A , B and  FIG. 29 , respectively). The Cys residues targeted by DMF exhibited concentration- ( FIG. 27C  and Tables 8-9) and time ( FIG. 27D ) dependent increases in DMF sensitivity, as revealed by isoTOP-ABPP experiments performed with human T cells treated with lower concentrations of DMF (10 and 25 μM, 4 h) or for shorter periods of time (50 μM DMF, 1 or 2 h). Of note, very few DMF-sensitive Cys residues were detected in T cells treated with 10 μM DMF, a concentration of the drug that also had limited impact T cell activation ( FIG. 23B , D, E). These concentration- and time-dependent studies uncovered another ˜10 DMF sensitive Cys residues that were not detected in the original 50 μM/4 h isoTOP-ABPP experiments, likely reflecting the stochastic nature of peptide discovery in data dependent MS experiments. 
     The possibility that some of the alterations in Cys reactivity following DMF treatment could reflect changes in protein expression was considered; however, multiple Cys residues were quantified by isoTOP-ABPP for the majority of proteins harboring DMF-sensitive Cys residues, and, in most of these cases, the additional quantified Cys residues were clearly unaffected by DMF treatment ( FIG. 27E ). The DNA activated protein kinase PRKDC was shown as one representative example, for which IA-alkyne reactivity was quantified for several Cys residues, only one of which (C4045) was blocked by DMF ( FIG. 27F ). These results indicate that DMF directly impaired the IA alkyne reactivity of specific Cys residues rather than indirectly affecting protein expression in human T cells. 
     Conservation of DMF-Sensitive Cys Residues in Human and Mouse T Cells 
     Considering that DMF impaired the activation of both human and mouse T cells, it was surmised that at least a subset of Cys residues potentially important for mediating DMF action were conserved in humans and mice. Consistent with this, approximately two-thirds of the DMF-sensitive Cys residues discovered in human T cells are conserved in mice ( FIG. 30A  and Table 7). The isoTOP-ABPP experiments were performed on mouse T cells treated with DMF (50 μM, 4 h) and found that the vast majority (&gt;80%) of the conserved, quantified Cys residues sensitive to DMF in human T cells were also blocked (R values&gt;4) by this drug in mouse T cells ( FIG. 30B  and Tables 8-9). These results indicate that DMF targets a similar array of Cys residues in human and mouse T cells, pointing to a specific set of proteins as candidate sites of action for this electrophilic drug. 
     The proteins containing DMF-sensitive Cys residues, as a whole, originated from several functional classes, including enzymes, channels, transporters, scaffolding proteins, and transcriptional regulators ( FIG. 30C ). Among these proteins were several with important immune functions (Table 7). DMF-sensitive Cys residues were found, for instance, in multiple proteins that are either components or regulators of the NF-κB signaling pathway, including IκB kinase β (IKKβ or IKBKB), protein kinase C-θ (PKCθ or PRKCQ), and TNFAIP3 (Table 7). Consistent with these sites of DMF action and potentially others within the NF-κB pathway, it was found that DMF treatment blocked p65 nuclear translocation ( FIG. 31 ), as has been shown in other cell types. DMF-sensitive Cys residues were also found in: 1) the adenosine deaminase enzyme ADA, deleterious mutations in which cause severe combined immunodeficiency in humans, 2) the transcription factors interferon regulatory factors-4 (IRF4) and -8 (IRF8), and 3) the immunomodulatory cytokine IL-16 (Table 7). 
     DMF Perturbs a CXXC Motif Critical for PKCθ-CD28 Interactions and T Cell Activation 
     PKCθ is a key kinase involved in T cell signaling at the immunological synapse where engagement of the T cell receptor and CD28 co-receptor initiates activation of multiple downstream pathways, including NF-κB. T cells from PKCθ(−/−) mice are defective in early activation. The isoTOP-ABPP analysis identified two DMF sensitive Cys residues—C14 and C17—in human ( FIG. 32A ) and mouse ( FIG. 33A ) T cells, and these Cys residues showed time- and concentration-dependent increases in DMF sensitivity ( FIG. 33B , C), but were not affected by MMF treatment ( FIG. 33D ). Because C14 and C17 are found on the same tryptic peptide, it was difficult to distinguish whether one or both residues was sensitive to DMF treatment, but, in certain isoTOP-ABPP experiments, this tryptic peptide appeared to migrate as two adjacent peaks, both of which showed DMF sensitivity ( FIG. 32A ), suggesting that the IA-alkyne reactivity of both C14 and C17 is blocked by DMF treatment. The isoTOP-ABPP experiments also identified a third Cys in PKCθ (C322) that was unaffected by DMF treatment ( FIG. 32A ), indicating that DMF caused reductions in C14/17 reactivity rather than changes in PKCθ expression. C14 and C17 form a CXXC motif found in the C2 domain of PKCθ, but not other PKC isoforms ( FIG. 32B , C). The C2 domain of PKCθ was recently shown to bind phosphotyrosine-containing peptides and has been postulated to stabilize plasma membrane association of PKCθ at the immunological synapse. Upon TCR/CD28 stimulation, PKCθ is recruited to the immunological synapse where it interacts with the CD28 co-receptor by associating with the CD28 cytoplasmic tail. It was found that DMF, but not MMF, blocked the interaction between PKCθ and CD28 in mouse T cells ( FIG. 32D ). A retroviral transduction was used to reconstitute PKCθ(−/−) T cells with either WT- or a C14S/C17S-PKCθ mutant and found that the mutant protein failed to associate with CD28 ( FIG. 32E ). PKCθ(−/−) T cells reconstituted with the C14S/C17SPKCθ mutant also showed impaired expression of CD25 ( FIG. 32F ) and IL-2 release ( FIG. 32G ) compared to cells reconstituted with WT PKCθ following anti-CD3, anti-CD28 treatment. Taken together, these data indicate that the C14/C17 motif within the C2 domain of PKCθ regulates localization of this kinase to the immunological synapse, and disruption of this motif by DMF or genetic mutation impairs T cell activation. 
     Sensitive Cysteine Residue Sites in DMF Toward Probe ADA 
     The DMFsensitive Cys residue C75 is located between two amino acids—G74 and R76—that, when mutated in humans, contribute to an immunosuppressive phenotype. The amino acid 74-76 region of ADA is over 25 angstroms from the active site of the enzyme ( FIG. 34 ), suggesting that it performs a non-catalytic function possibly perturbed by DMF reactivity. The DMF-sensitive Cys in IKBKB is located in the leucine-zipper domain and is distinct from another electrophile-sensitive Cys residue C179 found in the active site of this kinase. 
     Table 1 illustrates a list of liganded cysteines and their reactivity profiles with the fragment electrophile library from isoTOP-ABPP experiments performed in cell lysates (in vitro). Table 1 further shows the accession number (or the protein identifier) of the protein. 
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 1A 
               
               
                   
               
             
            
               
                   
                   
                 SEQ 
                   
                   
               
               
                   
                   
                 ID 
                 2_500μM —   
                 2_500μM —   
               
               
                 Identifier 
                 Protein 
                 NO: 
                 invitro_231 
                 invitro_ramos 
               
               
                   
               
               
                 Q99873_C109 
                 PRMT1 Protein arginine 
                 17 
                  3.1 
                 12.6  
               
               
                   
                 N-methyltransferase 1 
               
               
                 P24752_C119 
                 ACAT1 Acetyl-CoA 
                 22 
                  3.9 
                 3.2 
               
               
                   
                 acetyltransferase, mitochondrial 
               
               
                 P09211_C48 
                 GSTP1 Glutathione S- 
                 25 
                  3.1 
                 1.6 
               
               
                   
                 transferase P 
               
               
                 O14980_C34 
                 XPO1 Exportin-1 
                 28 
                  2.8 
                 4.6 
               
               
                 P24752_C196 
                 ACAT1 Acetyl-CoA 
                 33 
                 12.4 
                 9.3 
               
               
                   
                 acetyltransferase, mitochondrial 
               
               
                 Q15084_C55 
                 PDIA6 Protein disulfide-isomerase A6 
                 51 
                  6.3 
                 7.1 
               
               
                 P24752_C413 
                 ACAT1 Acetyl-CoA 
                 56 
                 18.1 
                 — 
               
               
                   
                 acetyltransferase, mitochondrial 
               
               
                 P63244_C182 
                 GNB2L1 Guanine nucleotide-binding 
                 85 
                  1.2 
                 1.2 
               
               
                   
                 protein subunit beta-2- 
               
               
                 P24752_C126 
                 ACAT1 Acetyl-CoA 
                 89 
                 20.0 
                 — 
               
               
                   
                 acetyltransferase, mitochondrial 
               
               
                 Q15084_C190 
                 PDIA6 Protein disulfide-isomerase 
                 96 
                 — 
                 15.4  
               
               
                   
                 A6 
               
               
                 Q8TAQ2_C145 
                 SMARCC2 SWI/SNF complex 
                 119 
                  8.5 
                 14.0  
               
               
                   
                 subunit SMARCC2 
               
               
                 P68036_C86 
                 UBE2L3 Ubiquitin-conjugating 
                 120 
                  2.8 
                 2.5 
               
               
                   
                 enzyme E2 L3 
               
               
                 P15374_C95 
                 UCHL3 Ubiquitin carboxyl-terminal 
                 146 
                 — 
                 1.8 
               
               
                   
                 hydrolase isozyme L3 
               
               
                 Q16763_C118 
                 UBE2S Ubiquitin-conjugating 
                 187 
                  4.2 
                 6.9 
               
               
                   
                 enzyme E2 S 
               
               
                 Q16822_C306 
                 PCK2 Phosphoenolpyruvate 
                 192 
                 — 
                 — 
               
               
                   
                 carboxykinase 
               
               
                 O14980_C528 
                 XPO1 Exportin-1 DLLGLCEQK 
                 218 
                  4.9 
                 3.1 
               
               
                   
                 K.DLLGLC*EQKR.G 
               
               
                 O00170_C122 
                 AIP AH receptor-interacting 
                 240 
                 12.5 
                 6.7 
               
               
                   
                 protein 
               
               
                 O75874_C269 
                 IDH1 Isocitrate dehydrogenase 
                 260 
                 20.0 
                 — 
               
               
                 O75362_C286 
                 ZNF217 Zinc finger protein 217 
                 268 
                 20.0 
                 20.0  
               
               
                 P40763_C259 
                 STAT3 Signal transducer and 
                 283 
                 — 
                 — 
               
               
                   
                 activator of transcription 3 
               
               
                 Q9Y3Z3_C522 
                 SAMHD1 SAM domain and HD 
                 288 
                 — 
                 4.0 
               
               
                   
                 domain-containing protein 1 
               
               
                 P16455_C150 
                 MGMT Methylated-DNA--protein-cysteine 
                 291 
                 — 
                 20.0  
               
               
                   
                 methyltransferase 
               
               
                 Q96GG9_C115 
                 DCUN1D1 DCN1-like protein 1 
                 293 
                 — 
                 20.0  
               
               
                 P00813_C75 
                 ADA Adenosine deaminase 
                 296 
                 — 
                 7.3 
               
               
                 Q14790_C360 
                 CASP8 Caspase-8 
                 335 
                  9.8 
                 — 
               
               
                 Q15306_C194 
                 IRF4 Interferon regulatory 
                 338 
                 — 
                 — 
               
               
                   
                 factor 4 
               
               
                 Q6L8Q7_C108 
                 PDE12 2,5-phosphodiesterase 12 
                 339 
                 — 
                 5.1 
               
               
                 P48735_C308 
                 IDH2 Isocitrate dehydrogenase 
                 360 
                  1.4 
                 — 
               
               
                 Q86UV5_C39 
                 USP48 Ubiquitin carboxyl-terminal 
                 381 
                 — 
                 7.1 
               
               
                   
                 hydrolase 48 
               
               
                 P50851_C1704 
                 LRBA. Lipopolysaccharide-responsive 
                 388 
                 — 
                 3.4 
               
               
                   
                 and beige-like ancho 
               
               
                 O94953_C694 
                 KDM4B Lysine-specific 
                 395 
                 20.0 
                 5.1 
               
               
                   
                 demethylase 4B 
               
               
                 P19447_C342 
                 ERCC3 TFIIH basal 
                 402 
                 20.0 
                 — 
               
               
                   
                 transcription factor 
               
               
                   
                 complex helicase 
               
               
                 Q00535_C157 
                 CDK5 Cyclin-dependent kinase 5 
                 407 
                 — 
                 3.2 
               
               
                 Q9UPT9_C171 
                 USP22 Ubiquitin carboxyl- 
                 413 
                 — 
                 7.1 
               
               
                   
                 terminal hydrolase 22 
               
               
                 Q9HB90_C377 
                 RRAGC Ras-related GTP-binding 
                 417 
                 20.0 
                 — 
               
               
                   
                 protein C 
               
               
                 P50851_C2675 
                 LRBA Lipopolysaccharide-responsive 
                 426 
                 — 
                 3.0 
               
               
                   
                 and beige-like ancho 
               
               
                 Q9NYL2_C22 
                 MLTK Mitogen-activated protein 
                 430 
                 20.0 
                 — 
               
               
                   
                 kinase kinase kinase MLT 
               
               
                 Q5T1V6_C414 
                 DDX59 Probable ATP-dependent 
                 439 
                 20.0 
                 20.0  
               
               
                   
                 RNA helicase DDX59 
               
               
                 Q9HB90_C358 
                 RRAGC Ras-related GTP-binding 
                 452 
                 20.0 
                 20.0  
               
               
                   
                 protein C 
               
               
                 P16455_C145 
                 MGMT Methylated-DNA--protein-cysteine 
                 470 
                 — 
                 20.0  
               
               
                   
                 methyltransferase 
               
               
                 Q9Y5T5_C205 
                 USP16 Ubiquitin carboxyl-terminal 
                 474 
                 20.0 
                 — 
               
               
                   
                 hydrolase 16 
               
               
                 Q02556_C306 
                 IRF8 Interferon regulatory factor 8 
                 513 
                 — 
                 — 
               
               
                 Q15910_C503 
                 EZH2 Histone-lysine 
                 557 
                 — 
                 2.8 
               
               
                   
                 N-methyltransferase EZH2 
               
               
                 Q96RU2_C171 
                 USP28 Ubiquitin carboxyl- 
                 569 
                 — 
                 1.1 
               
               
                   
                 terminal hydrolase 28 
               
               
                 Q16877_C159 
                 PFKFB4 6-phosphofructo-2- 
                 582 
                 — 
                 — 
               
               
                   
                 kinase/fructose-2,6-bisphosphata 
               
               
                 P04150_C302 
                 NR3C1 Glucocorticoid receptor 
                 600 
                  2.3 
                 — 
               
               
                 Q96JH7_C219 
                 VCPIP1 Deubiquitinating protein 
                 601 
                 — 
                 1.1 
               
               
                   
                 VCIP135 
               
               
                 P48200_C137 
                 IREB2 Iron-responsive 
                 603 
                 — 
                 10.5  
               
               
                   
                 element-binding protein 2 
               
               
                 O00622_C39 
                 CYR61 Protein CYR61 
                 612 
                 — 
                 — 
               
               
                 P24752_C196 
                 ACAT1 Acetyl-CoA 
                 33 
                 12.4 
                 9.3 
               
               
                   
                 acetyltransferase, mitochondrial 
               
               
                 Q15084_C55 
                 PDIA6 Protein disulfide-isomerase 
                 51 
                  6.3 
                 7.1 
               
               
                   
                 A6 
               
               
                 P24752_C413 
                 ACAT1 Acetyl-CoA 
                 56 
                 18.1 
                 — 
               
               
                   
                 acetyltransferase, mitochondrial 
               
               
                 P63244_C182 
                 GNB2L1 Guanine nucleotide-binding 
                 85 
                  1.2 
                 1.2 
               
               
                   
                 protein subunit beta-2- 
               
               
                 P24752_C126 
                 ACAT1 Acetyl-CoA 
                 89 
                 20.0 
                 — 
               
               
                   
                 acetyltransferase, mitochondrial 
               
               
                 Q15084_C190 
                 PDIA6 Protein disulfide-isomerase 
                 96 
                 — 
                 15.4  
               
               
                   
                 A6 
               
               
                 Q8TAQ2_C145 
                 SMARCC2 SWI/SNF complex 
                 119 
                  8.5 
                 14.0  
               
               
                   
                 subunit SMARCC2 
               
               
                 P68036_C86 
                 UBE2L3 Ubiquitin-conjugating 
                 120 
                  2.8 
                 2.5 
               
               
                   
                 enzyme E2 L3 
               
               
                 P15374_C95 
                 UCHL3 Ubiquitin carboxyl-terminal 
                 146 
                 — 
                 1.8 
               
               
                   
                 hydrolase isozyme L3 
               
               
                 Q16763_C118 
                 UBE2S Ubiquitin-conjugating 
                 187 
                  4.2 
                 6.9 
               
               
                   
                 enzyme E2 S 
               
               
                 Q16822_C306 
                 PCK2 Phosphoenolpyruvate 
                 192 
                 — 
                 — 
               
               
                   
                 carboxy kinase 
               
               
                 O14980_C528 
                 XPO1 Exportin-1 DLLGLCEQK 
                 218 
                  4.9 
                 3.1 
               
               
                   
                 K.DLLGLC*EQKR.G 
               
               
                 O00170_C122 
                 AIP AH receptor-interacting 
                 240 
                 12.5 
                 6.7 
               
               
                   
                 protein 
               
               
                 O75874_C269 
                 IDH1 Isocitrate dehydrogenase 
                 260 
                 20.0 
                 — 
               
               
                 O75362_C286 
                 ZNF217 Zinc finger protein 217 
                 268 
                 20.0 
                 20.0  
               
               
                 P40763_C259 
                 STAT3 Signal transducer and 
                 283 
                 — 
                 — 
               
               
                   
                 activator of transcription 3 
               
               
                 Q9Y3Z3_C522 
                 SAMHD1 SAM domain and HD 
                 288 
                 — 
                 4.0 
               
               
                   
                 domain-containing protein 1 
               
               
                 P16455_C150 
                 MGMT Methylated-DNA-protein-cysteine 
                 291 
                 — 
                 20.0  
               
               
                   
                 methyltransferase 
               
               
                 Q96GG9_C115 
                 DCUN1D1 DCN1-like protein 1 
                 293 
                 — 
                 20.0  
               
               
                 P00813_C75 
                 ADA Adenosine deaminase 
                 296 
                 — 
                 7.3 
               
               
                 Q14790_C360 
                 CASP8 Caspase-8 
                 335 
                  9.8 
                 — 
               
               
                 Q15306_C194 
                 IRF4 Interferon regulatory factor 4 
                 338 
                 — 
                 — 
               
               
                 Q6L8Q7_C108 
                 PDE12 2,5-phosphodiesterase 12 
                 339 
                 — 
                 5.1 
               
               
                 P48735_C308 
                 IDH2 Isocitrate dehydrogenase 
                 360 
                  1.4 
                 — 
               
               
                 Q86UV5_C39 
                 USP48 Ubiquitin carboxyl-terminal 
                 381 
                 — 
                 7.1 
               
               
                   
                 hydrolase 48 
               
               
                 P50851_C1704 
                 LRBA Lipopolysaccharide- 
                 388 
                 — 
                 3.4 
               
               
                   
                 responsive and beige-like ancho 
               
               
                 O94953_C694 
                 KDM4B Lysine-specific 
                 395 
                 20.0 
                 5.1 
               
               
                   
                 demethylase 4B 
               
               
                 P19447_C342 
                 ERCC3 TFIIH basal transcription 
                 402 
                 20.0 
                 — 
               
               
                   
                 factor complex helicase 
               
               
                 Q00535_C157 
                 CDK5 Cyclin-dependent kinase 5 
                 407 
                 — 
                 3.2 
               
               
                 Q9UPT9_C171 
                 USP22 Ubiquitin carboxyl-terminal 
                 413 
                 — 
                 7.1 
               
               
                   
                 hydrolase 22 
               
               
                 Q9HB90_C377 
                 RRAGC Ras-related GTP-binding 
                 417 
                 20.0 
                 — 
               
               
                   
                 protein C 
               
               
                 P50851_C2675 
                 LRBA Lipopolysaccharide-responsive 
                 426 
                 — 
                 3.0 
               
               
                   
                 and beige-like ancho 
               
               
                 Q9NYL2_C22 
                 MLTK Mitogen-activated protein 
                 430 
                 20.0 
                 — 
               
               
                   
                 kinase kinase kinase MLT 
               
               
                 Q5T1V6_C414 
                 DDX59 Probable ATP-dependent 
                 439 
                 20.0 
                 20.0  
               
               
                   
                 RNA helicase DDX59 
               
               
                 Q9HB90_C358 
                 RRAGC Ras-related GTP-binding 
                 452 
                 20.0 
                 20.0  
               
               
                   
                 protein C 
               
               
                 P16455_C145 
                 MGMT Methylated-DNA-protein-cysteine 
                 470 
                 — 
                 20.0  
               
               
                   
                 methyltransferase 
               
               
                 Q9Y5T5_C205 
                 USP16 Ubiquitin carboxyl-terminal 
                 474 
                 20.0 
                 — 
               
               
                   
                 hydrolase 16 
               
               
                 Q02556_C306 
                 IRF8 Interferon regulatory factor 
                 513 
                 — 
                 — 
               
               
                   
                 8 
               
               
                 Q15910_C503 
                 EZH2 Histone-lysine 
                 557 
                 — 
                 2.8 
               
               
                   
                 N methyltransferase EZH2 
               
               
                 Q96RU2_C171 
                 USP28 Ubiquitin carboxyl-terminal 
                 569 
                 — 
                 1.1 
               
               
                   
                 hydrolase 28 
               
               
                 Q16877_C159 
                 PFKFB4 6-phosphofructo-2- 
                 582 
                 — 
                 — 
               
               
                   
                 kinase/fructose-2,6-bisphosphata 
               
               
                 P04150_C302 
                 NR3C1 Glucocorticoid receptor 
                 600 
                  2.3 
                 — 
               
               
                 Q96JH7_C219 
                 VCPIP1 Deubiquitinating protein 
                 601 
                 — 
                 1.1 
               
               
                   
                 VCIP135 
               
               
                 P48200_C137 
                 IREB2 Iron-responsive 
                 603 
                 — 
                 10.5  
               
               
                   
                 element-binding protein 2 
               
               
                 O00622_C39 
                 CYR61 Protein CYR61 
                 612 
                 — 
                 — 
               
               
                 Q5T1V6_C453 
                 DDX59 Probable ATP-dependent 
                 620 
                 20.0 
                 20.0  
               
               
                   
                 RNA helicase DDX59 
               
               
                 P51617_C608 
                 IRAK1 Interleukin-1 
                 656 
                 — 
                 2.5 
               
               
                   
                 receptor-associated kinase 1 
               
               
                 P42575_C370 
                 CASP2 Caspase-2 
                 661 
                 — 
                 — 
               
               
                 P09086_C346 
                 POU2F2 POU domain, class 2, 
                 663 
                 — 
                 — 
               
               
                   
                 transcription factor 2 
               
               
                 Q09472_C1738 
                 EP300 Histone acetyltransferase 
                 676 
                 — 
                 12.7  
               
               
                   
                 p300 
               
               
                 Q01201_C109 
                 RELB Transcription factor RelB 
                 681 
                 20.0 
                 20.0  
               
               
                 Q70CQ2_C741 
                 USP34 Ubiquitin carboxyl-terminal 
                 688 
                 — 
                 — 
               
               
                   
                 hydrolase 34 
               
               
                 P41226_C599 
                 UBA7 Ubiquitin-like 
                 702 
                 — 
                 — 
               
               
                   
                 modifier-activating enzyme 7 
               
               
                 P14598_C378 
                 NCF1 Neutrophil cytosol factor 1 
                 705 
                 — 
                 4.4 
               
               
                 Q9C0C9_C375 
                 UBE2O Ubiquitin-conjugating 
                 707 
                 — 
                 — 
               
               
                   
                 enzyme E2O 
               
               
                 O00622_C134 
                 CYR61 Protein CYR61 
                 713 
                 — 
                 — 
               
               
                 O00541_C361 
                 PES1 Pescadillo homolog 
                 718 
                 — 
                 — 
               
               
                 P43403_C117 
                 ZAP70 Tyrosine-protein kinase 
                 726 
                 — 
                 — 
               
               
                   
                 ZAP-70 
               
               
                 Q96FA3_C282 
                 PELI1 E3 ubiquitin-protein ligase 
                 729 
                 — 
                 — 
               
               
                   
                 pellino homolog 1 
               
               
                 Q9UPT9_C44 
                 USP22 Ubiquitin carboxyl-terminal 
                 737 
                 — 
                 — 
               
               
                   
                 hydrolase 22 
               
               
                 Q9Y4C1_C251 
                 KDM3A Lysine-specific 
                 753 
                 — 
                 — 
               
               
                   
                 demethylase 3A 
               
               
                 Q70CQ2_C1090 
                 USP34 Ubiquitin carboxyl-terminal 
                 761 
                 — 
                 — 
               
               
                   
                 hydrolase 34 
               
               
                 O00622_C70 
                 CYR61 Protein CYR61 
                 762 
                 — 
                 — 
               
               
                 P04150_C622 
                 NR3C1 Glucocorticoid receptor 
                 765 
                 — 
                 — 
               
               
                   
               
            
           
           
               
               
               
               
               
               
            
               
                   
                   
                 3_500μM —   
                 3_500μM —   
                 4_250μM —   
                 4_250μM —   
               
               
                   
                 Identifier 
                 invitro_231 
                 invitro_ramos 
                 invitro_231 
                 invitro_ramos 
               
               
                   
                   
               
               
                   
                 Q99873_C109 
                 1.3 
                 1.8 
                 1.1 
                 0.2 
               
               
                   
                 P24752_C119 
                 2.1 
                 5.3 
                 1.8 
                 0.2 
               
               
                   
                 P09211_C48 
                 2.9 
                 1.7 
                 3.2 
                 0.5 
               
               
                   
                 O14980_C34 
                 1.4 
                 1.6 
                 1.0 
                 0.2 
               
               
                   
                 P24752_C196 
                 1.7 
                 3.1 
                 1.9 
                 0.5 
               
               
                   
                 Q15084_C55 
                 17.9  
                 14.9  
                 1.3 
                 1.2 
               
               
                   
                 P24752_C413 
                 15.3  
                 20.0  
                 3.3 
                 — 
               
               
                   
                 P63244_C182 
                 20.0  
                 4.7 
                 0.9 
                 — 
               
               
                   
                 P24752_C126 
                 2.6 
                 2.4 
                 2.1 
                 1.2 
               
               
                   
                 Q15084_C190 
                 19.9  
                 13.1  
                 1.8 
                 1.2 
               
               
                   
                 Q8TAQ2_C145 
                 9.7 
                 6.6 
                 1.3 
                 — 
               
               
                   
                 P68036_C86 
                 1.2 
                 3.0 
                 1.2 
                 — 
               
               
                   
                 P15374_C95 
                 1.7 
                 1.4 
                 — 
                 0.9 
               
               
                   
                 Q16763_C118 
                 1.3 
                 1.5 
                 1.2 
                 — 
               
               
                   
                 Q16822_C306 
                 10.6  
                 0.9 
                 2.2 
                 — 
               
               
                   
                 O14980_C528 
                 20.0  
                 20.0  
                 0.9 
                 1.1 
               
               
                   
                 O00170_C122 
                 7.0 
                 3.1 
                 2.5 
                 0.3 
               
               
                   
                 O75874_C269 
                 20.0  
                 1.0 
                 1.6 
                 0.6 
               
               
                   
                 O75362_C286 
                 1.4 
                 — 
                 1.7 
                 — 
               
               
                   
                 P40763_C259 
                 2.5 
                 2.9 
                 2.0 
                 1.9 
               
               
                   
                 Q9Y3Z3_C522 
                 2.6 
                 — 
                 1.5 
                 — 
               
               
                   
                 P16455_C150 
                 — 
                 17.1  
                 — 
                 6.9 
               
               
                   
                 Q96GG9_C115 
                 — 
                 5.5 
                 — 
                 — 
               
               
                   
                 P00813_C75 
                 — 
                 1.5 
                 — 
                 0.1 
               
               
                   
                 Q14790_C360 
                 3.3 
                 2.3 
                 12.3  
                 — 
               
               
                   
                 Q15306_C194 
                 — 
                 20.0  
                 — 
                 — 
               
               
                   
                 Q6L8Q7_C108 
                 3.6 
                 1.8 
                 — 
                 — 
               
               
                   
                 P48735_C308 
                 2.2 
                 — 
                 0.7 
                 — 
               
               
                   
                 Q86UV5_C39 
                 1.8 
                 1.5 
                 1.4 
                 1.4 
               
               
                   
                 P50851_C1704 
                 — 
                 3.6 
                 — 
                 1.5 
               
               
                   
                 O94953_C694 
                 20.0  
                 7.4 
                 20.0  
                 — 
               
               
                   
                 P19447_C342 
                 12.1  
                 — 
                 1.6 
                 1.1 
               
               
                   
                 Q00535_C157 
                 — 
                 20.0  
                 — 
                 1.3 
               
               
                   
                 Q9UPT9_C171 
                 — 
                 — 
                 — 
                 4.0 
               
               
                   
                 Q9HB90_C377 
                 3.7 
                 — 
                 3.5 
                 — 
               
               
                   
                 P50851_C2675 
                 — 
                 5.1 
                 1.1 
                 — 
               
               
                   
                 Q9NYL2_C22 
                 1.8 
                 — 
                 20.0  
                 — 
               
               
                   
                 Q5T1V6_C414 
                 — 
                 6.0 
                 — 
                 — 
               
               
                   
                 Q9HB90_C358 
                 1.2 
                 — 
                 1.5 
                 — 
               
               
                   
                 P16455_C145 
                 — 
                 20.0  
                 — 
                 20.0  
               
               
                   
                 Q9Y5T5_C205 
                 — 
                 8.8 
                 — 
                 20.0  
               
               
                   
                 Q02556_C306 
                 — 
                 5.6 
                 — 
                 — 
               
               
                   
                 Q15910_C503 
                 — 
                 2.0 
                 — 
                 1.5 
               
               
                   
                 Q96RU2_C171 
                 — 
                 1.7 
                 — 
                 — 
               
               
                   
                 Q16877_C159 
                 — 
                 12.9  
                 1.4 
                 — 
               
               
                   
                 P04150_C302 
                 7.6 
                 — 
                 — 
                 — 
               
               
                   
                 Q96JH7_C219 
                 20.0  
                 15.1  
                 — 
                 — 
               
               
                   
                 P48200_C137 
                 — 
                 — 
                 — 
                 — 
               
               
                   
                 O00622_C39 
                 4.0 
                 — 
                 2.8 
                 — 
               
               
                   
                 P24752_C196 
                 1.7 
                 3.1 
                 1.9 
                 0.5 
               
               
                   
                 Q15084_C55 
                 17.9  
                 14.9  
                 1.3 
                 1.2 
               
               
                   
                 P24752_C413 
                 15.3  
                 20.0  
                 3.3 
                 — 
               
               
                   
                 P63244_C182 
                 20.0  
                 4.7 
                 0.9 
                 — 
               
               
                   
                 P24752_C126 
                 2.6 
                 2.4 
                 2.1 
                 1.2 
               
               
                   
                 Q15084_C190 
                 19.9  
                 13.1  
                 1.8 
                 1.2 
               
               
                   
                 Q8TAQ2_C145 
                 9.7 
                 6.6 
                 1.3 
                 — 
               
               
                   
                 P68036_C86 
                 1.2 
                 3.0 
                 1.2 
                 — 
               
               
                   
                 P15374_C95 
                 1.7 
                 1.4 
                 — 
                 0.9 
               
               
                   
                 Q16763_C118 
                 1.3 
                 1.5 
                 1.2 
                 — 
               
               
                   
                 Q16822_C306 
                 10.6  
                 0.9 
                 2.2 
                 — 
               
               
                   
                 O14980_C528 
                 20.0  
                 20.0  
                 0.9 
                 1.1 
               
               
                   
                 O00170_C122 
                 7.0 
                 3.1 
                 2.5 
                 0.3 
               
               
                   
                 O75874_C269 
                 20.0  
                 1.0 
                 1.6 
                 0.6 
               
               
                   
                 O75362_C286 
                 1.4 
                 — 
                 1.7 
                 — 
               
               
                   
                 P40763_C259 
                 2.5 
                 2.9 
                 2.0 
                 1.9 
               
               
                   
                 Q9Y3Z3_C522 
                 2.6 
                 — 
                 1.5 
                 — 
               
               
                   
                 P16455_C150 
                 — 
                 17.1  
                 — 
                 6.9 
               
               
                   
                 Q96GG9_C115 
                 — 
                 5.5 
                 — 
                 — 
               
               
                   
                 P00813_C75 
                 — 
                 1.5 
                 — 
                 0.1 
               
               
                   
                 Q14790_C360 
                 3.3 
                 2.3 
                 12.3  
                 — 
               
               
                   
                 Q15306_C194 
                 — 
                 20.0  
                 — 
                 — 
               
               
                   
                 Q6L8Q7_C108 
                 3.6 
                 1.8 
                 — 
                 — 
               
               
                   
                 P48735_C308 
                 2.2 
                 — 
                 0.7 
                 — 
               
               
                   
                 Q86UV5_C39 
                 1.8 
                 1.5 
                 1.4 
                 1.4 
               
               
                   
                 P50851_C1704 
                 — 
                 3.6 
                 — 
                 1.5 
               
               
                   
                 O94953_C694 
                 20.0  
                 7.4 
                 20.0  
                 — 
               
               
                   
                 P19447_C342 
                 12.1  
                 — 
                 1.6 
                 1.1 
               
               
                   
                 Q00535_C157 
                 — 
                 20.0  
                 — 
                 1.3 
               
               
                   
                 Q9UPT9_C171 
                 — 
                 — 
                 — 
                 4.0 
               
               
                   
                 Q9HB90_C377 
                 3.7 
                 — 
                 3.5 
                 — 
               
               
                   
                 P50851_C2675 
                 — 
                 5.1 
                 1.1 
                 — 
               
               
                   
                 Q9NYL2_C22 
                 1.8 
                 — 
                 20.0  
                 — 
               
               
                   
                 Q5T1V6_C414 
                 — 
                 6.0 
                 — 
                 — 
               
               
                   
                 Q9HB90_C358 
                 1.2 
                 — 
                 1.5 
                 — 
               
               
                   
                 P16455_C145 
                 — 
                 20.0  
                 — 
                 20.0  
               
               
                   
                 Q9Y5T5_C205 
                 — 
                 8.8 
                 — 
                 20.0  
               
               
                   
                 Q02556_C306 
                 — 
                 5.6 
                 — 
                 — 
               
               
                   
                 Q15910_C503 
                 — 
                 2.0 
                 — 
                 1.5 
               
               
                   
                 Q96RU2_C171 
                 — 
                 1.7 
                 — 
                 — 
               
               
                   
                 Q16877_C159 
                 — 
                 12.9  
                 1.4 
                 — 
               
               
                   
                 P04150_C302 
                 7.6 
                 — 
                 — 
                 — 
               
               
                   
                 Q96JH7_C219 
                 20.0  
                 15.1  
                 — 
                 — 
               
               
                   
                 P48200_C137 
                 — 
                 — 
                 — 
                 — 
               
               
                   
                 O00622_C39 
                 4.0 
                 — 
                 2.8 
                 — 
               
               
                   
                 Q5T1V6_C453 
                 20.0  
                 — 
                 — 
                 — 
               
               
                   
                 P51617_C608 
                 — 
                 20.0  
                 — 
                 — 
               
               
                   
                 P42575_C370 
                 — 
                 7.4 
                 — 
                 — 
               
               
                   
                 P09086_C346 
                 1.7 
                 5.5 
                 — 
                 — 
               
               
                   
                 Q09472_C1738 
                 — 
                 — 
                 — 
                 — 
               
               
                   
                 Q01201_C109 
                 — 
                 — 
                 — 
                 — 
               
               
                   
                 Q70CQ2_C741 
                 — 
                 3.2 
                 — 
                 — 
               
               
                   
                 P41226_C599 
                 — 
                 — 
                 — 
                 20.0  
               
               
                   
                 P14598_C378 
                 — 
                 2.1 
                 — 
                 1.4 
               
               
                   
                 Q9C0C9_C375 
                 9.8 
                 4.1 
                 — 
                 — 
               
               
                   
                 O00622_C134 
                 20.0  
                 — 
                 — 
                 — 
               
               
                   
                 O00541_C361 
                 1.5 
                 — 
                 — 
                 — 
               
               
                   
                 P43403_C117 
                 — 
                 — 
                 — 
                 — 
               
               
                   
                 Q96FA3_C282 
                 — 
                 — 
                 — 
                 — 
               
               
                   
                 Q9UPT9_C44 
                 — 
                 — 
                 — 
                 — 
               
               
                   
                 Q9Y4C1_C251 
                 4.4 
                 4.0 
                 — 
                 — 
               
               
                   
                 Q70CQ2_C1090 
                 — 
                 19.7  
                 — 
                 — 
               
               
                   
                 O00622_C70 
                 20.0  
                 — 
                 — 
                 — 
               
               
                   
                 P04150_C622 
                 20.0  
                 — 
                 — 
                 — 
               
               
                   
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
               
               
             
               
                 TABLE 1B 
               
               
                   
               
             
            
               
                   
                 5_500μM —   
                 5_500μM —   
                 6_500μM —   
                 7_500μM —   
                 7_500μM —   
                 8_500μM —   
               
               
                 Identifier 
                 invitro_231 
                 invitro_ramos 
                 invitro_231 
                 invitro_231 
                 invitro_ramos 
                 invitro_231 
               
               
                   
               
               
                 Q99873_C109 
                 0.9 
                 1.3 
                 1.1 
                 1.1 
                 1.1 
                 1.2 
               
               
                 P24752_C119 
                 1.8 
                 2.4 
                 1.1 
                 2.3 
                 2.0 
                 1.8 
               
               
                 P09211_C48 
                 2.2 
                 2.4 
                 1.2 
                 1.8 
                 0.9 
                 2.6 
               
               
                 O14980_C34 
                 1.1 
                 1.2 
                 1.2 
                 1.7 
                 1.8 
                 2.4 
               
               
                 P24752_C196 
                 1.5 
                 2.2 
                 1.0 
                 1.9 
                 — 
                 2.7 
               
               
                 Q15084_C55 
                 0.9 
                 1.1 
                 1.0 
                 1.0 
                 — 
                 4.7 
               
               
                 P24752_C413 
                 1.3 
                 — 
                 1.1 
                 4.2 
                 — 
                 1.4 
               
               
                 P63244_C182 
                 1.5 
                 1.4 
                 1.5 
                 1.5 
                 — 
                 0.9 
               
               
                 P24752_C126 
                 0.9 
                 1.3 
                 0.9 
                 2.2 
                 — 
                 2.1 
               
               
                 Q15084_C190 
                 — 
                 1.7 
                 1.1 
                 1.0 
                 1.2 
                 20.0  
               
               
                 Q8TAQ2_C145 
                 — 
                 2.8 
                 — 
                 1.0 
                 — 
                 3.1 
               
               
                 P68036_C86 
                 — 
                 4.8 
                 1.8 
                 0.9 
                 — 
                 1.4 
               
               
                 P15374_C95 
                 1.5 
                 1.1 
                 1.1 
                 0.8 
                 — 
                 20.0  
               
               
                 Q16763_C118 
                 2.8 
                 — 
                 — 
                 1.5 
                 — 
                 — 
               
               
                 Q16822_C306 
                 1.7 
                 — 
                 — 
                 1.4 
                 — 
                 2.2 
               
               
                 O14980_C528 
                 20.0  
                 — 
                 0.7 
                 0.7 
                 — 
                 1.8 
               
               
                 O00170_C122 
                 — 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 O75874_C269 
                 — 
                 0.8 
                 — 
                 1.2 
                 — 
                 12.4  
               
               
                 O75362_C286 
                 — 
                 — 
                 0.9 
                 1.3 
                 — 
                 1.8 
               
               
                 P40763_C259 
                 — 
                 — 
                 0.6 
                 1.3 
                 1.8 
                 1.8 
               
               
                 Q9Y3Z3_C522 
                 — 
                 5.4 
                 — 
                 — 
                 — 
                 1.8 
               
               
                 P16455_C150 
                 — 
                 9.6 
                 — 
                 — 
                 20.0  
                 — 
               
               
                 Q96GG9_C115 
                 — 
                 — 
                 — 
                 — 
                 1.6 
                 — 
               
               
                 P00813_C75 
                 — 
                 2.5 
                 — 
                 — 
                 1.4 
                 — 
               
               
                 Q14790_C360 
                 1.0 
                 1.3 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q15306_C194 
                 — 
                 2.2 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q6L8Q7_C108 
                 — 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 P48735_C308 
                 0.8 
                 — 
                 — 
                 0.9 
                 — 
                 1.3 
               
               
                 Q86UV5_C39 
                 — 
                 1.2 
                 — 
                 — 
                 — 
                 — 
               
               
                 P50851_C1704 
                 — 
                 3.6 
                 — 
                 1.8 
                 1.6 
                 — 
               
               
                 O94953_C694 
                 — 
                 — 
                 1.1 
                 — 
                 — 
                 20.0  
               
               
                 P19447_C342 
                 — 
                 4.1 
                 1.1 
                 1.3 
                 2.0 
                 5.9 
               
               
                 Q00535_C157 
                 — 
                 20.0  
                 — 
                 — 
                 — 
                 — 
               
               
                 Q9UPT9_C171 
                 — 
                 20.0  
                 — 
                 — 
                 3.2 
                 — 
               
               
                 Q9HB90_C377 
                 — 
                 — 
                 — 
                 — 
                 — 
                 5.1 
               
               
                 P50851_C2675 
                 — 
                 20.0  
                 — 
                 — 
                 — 
                 — 
               
               
                 Q9NYL2_C22 
                 20.0  
                 — 
                 — 
                 3.1 
                 — 
                 — 
               
               
                 Q5T1V6_C414 
                 — 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q9HB90_C358 
                 — 
                 — 
                 1.2 
                 — 
                 — 
                 — 
               
               
                 P16455_C145 
                 — 
                 2.0 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q9Y5T5_C205 
                 — 
                 1.1 
                 — 
                 — 
                 — 
                 — 
               
               
                 O00541_C272 
                 — 
                 12.3  
                 — 
                 — 
                 — 
                 — 
               
               
                 Q02556_C306 
                 — 
                 2.6 
                 — 
                 — 
                 20.0  
                 — 
               
               
                 Q15910_C503 
                 — 
                 20.0  
                 1.8 
                 — 
                 — 
                 — 
               
               
                 Q96RU2_C171 
                 — 
                 — 
                 0.8 
                 — 
                 — 
                 7.5 
               
               
                 Q16877_C159 
                 — 
                 20.0  
                 — 
                 — 
                 — 
                 — 
               
               
                 P04150_C302 
                 — 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q96JH7_C219 
                 — 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 P48200_C137 
                 — 
                 — 
                 — 
                 — 
                 2.2 
                 — 
               
               
                 O00622_C39 
                 — 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q5T1V6_C453 
                 — 
                 — 
                 — 
                 — 
                 — 
                 20.0  
               
               
                 P51617_C608 
                 — 
                 10.1  
                 — 
                 — 
                 — 
                 — 
               
               
                 P42575_C370 
                 — 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 P09086_C346 
                 — 
                 4.6 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q09472_C1738 
                 — 
                 20.0  
                 — 
                 — 
                 — 
                 — 
               
               
                 Q01201_C109 
                 — 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q70CQ2_C1741 
                 — 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 P41226_C599 
                 — 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 P14598_C378 
                 — 
                 4.0 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q9C0C9_C375 
                 — 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 O00622_C134 
                 — 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 O00541_C361 
                 — 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 P43403_C117 
                 — 
                 — 
                 — 
                 — 
                 — 
                 20.0  
               
               
                 Q96FA3_C282 
                 — 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q9UPT9_C44 
                 — 
                 20.0  
                 — 
                 — 
                 — 
                 — 
               
               
                 Q9Y4C1_C251 
                 — 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q700Q2_C1090 
                 — 
                 20.0  
                 — 
                 — 
                 — 
                 — 
               
               
                 O00622_C70 
                 — 
                 — 
                 — 
                 — 
                 — 
                 20.0  
               
               
                 P04150_C622 
                 — 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                   
               
            
           
           
               
               
               
               
               
               
            
               
                   
                   
                 8_500μM —   
                 9_500μM —   
                 9_500μM —   
                 10_500μM —   
               
               
                   
                 Identifier 
                 invito_ramos 
                 invitro_231 
                 invitro_ramos 
                 initro_231 
               
               
                   
                   
               
               
                   
                 Q99873_C109 
                 1.2 
                 1.0 
                 1.5 
                 2.3 
               
               
                   
                 P24752_C119 
                 0.7 
                 2.2 
                 3.1 
                 1.5 
               
               
                   
                 P09211_C48 
                 2.0 
                 2.3 
                 1.4 
                 1.4 
               
               
                   
                 O14980_C34 
                 1.5 
                 1.2 
                 1.1 
                 1.2 
               
               
                   
                 P24752_C196 
                 1.5 
                 3.1 
                 2.1 
                 2.5 
               
               
                   
                 Q15084_C55 
                 2.2 
                 1.4 
                 1.0 
                 20.0  
               
               
                   
                 P24752_C413 
                 2.1 
                 15.3  
                 — 
                 13.0  
               
               
                   
                 P63244_C182 
                 1.2 
                 0.9 
                 0.8 
                 1.1 
               
               
                   
                 P24752_C126 
                 12.6  
                 1.4 
                 — 
                 3.2 
               
               
                   
                 Q15084_C190 
                 2.7 
                 2.0 
                 1.3 
                 — 
               
               
                   
                 Q8TAQ2_C145 
                 1.7 
                 1.0 
                 1.6 
                 4.2 
               
               
                   
                 P68036_C86 
                 1.0 
                 0.8 
                 1.5 
                 1.1 
               
               
                   
                 P15374_C95 
                 1.2 
                 1.0 
                 1.2 
                 2.0 
               
               
                   
                 Q16763_C118 
                 1.1 
                 0.8 
                 1.0 
                 1.7 
               
               
                   
                 Q16822_C306 
                 1.0 
                 1.3 
                 — 
                 1.9 
               
               
                   
                 O14980_C528 
                 — 
                 0.8 
                 0.7 
                 0.8 
               
               
                   
                 O00170_C122 
                 1.3 
                 — 
                 1.1 
                 — 
               
               
                   
                 O75874_C269 
                 — 
                 — 
                 1.4 
                 20.0  
               
               
                   
                 O75362_C286 
                 — 
                 1.2 
                 — 
                 1.1 
               
               
                   
                 P40763_C259 
                 1.7 
                 1.5 
                 1.2 
                 3.4 
               
               
                   
                 Q9Y3Z3_C522 
                 1.1 
                 1.0 
                 — 
                 1.8 
               
               
                   
                 P16455_C150 
                 15.8  
                 — 
                 4.0 
                 — 
               
               
                   
                 Q96GG9_C115 
                 1.4 
                 — 
                 1.3 
                 1.3 
               
               
                   
                 P00813_C75 
                 1.3 
                 1.3 
                 1.1 
                 — 
               
               
                   
                 Q14790_C360 
                 1.4 
                 — 
                 — 
                 2.8 
               
               
                   
                 Q15306_C194 
                 2.1 
                 — 
                 1.1 
                 — 
               
               
                   
                 Q6L8Q7_C108 
                 — 
                 1.3 
                 — 
                 — 
               
               
                   
                 P48735_C308 
                 — 
                 1.4 
                 — 
                 1.1 
               
               
                   
                 Q86UV5_C39 
                 — 
                 0.8 
                 0.9 
                 2.5 
               
               
                   
                 P50851_C1704 
                 1.2 
                 1.0 
                 1.2 
                 — 
               
               
                   
                 O94953_C694 
                 1.1 
                 1.2 
                 1.0 
                 — 
               
               
                   
                 P19447_C342 
                 — 
                 2.5 
                 — 
                 3.0 
               
               
                   
                 Q00535_C157 
                 1.3 
                 1.2 
                 0.8 
                 — 
               
               
                   
                 Q9UPT9_C171 
                 2.3 
                 — 
                 — 
                 — 
               
               
                   
                 Q9HB90_C377 
                 — 
                 1.9 
                 — 
                 — 
               
               
                   
                 P50851_C2675 
                 1.1 
                 1.5 
                 — 
                 — 
               
               
                   
                 Q9NYL2_C22 
                 — 
                 20.0  
                 — 
                 — 
               
               
                   
                 Q5T1V6_C414 
                 2.0 
                 — 
                 — 
                 — 
               
               
                   
                 Q9HB90_C358 
                 — 
                 1.9 
                 — 
                 — 
               
               
                   
                 P16455_C145 
                 20.0  
                 — 
                 20.0  
                 — 
               
               
                   
                 Q9Y5T5_C205 
                 20.0  
                 — 
                 — 
                 — 
               
               
                   
                 O00541_C272 
                 1.6 
                 — 
                 — 
                 — 
               
               
                   
                 Q02556_C306 
                 2.2 
                 — 
                 1.0 
                 — 
               
               
                   
                 Q15910_C503 
                 — 
                 1.1 
                 — 
                 — 
               
               
                   
                 Q96RU2_C171 
                 — 
                 1.1 
                 — 
                 1.4 
               
               
                   
                 Q16877_C159 
                 1.0 
                 1.5 
                 — 
                 1.2 
               
               
                   
                 P04150_C302 
                 — 
                 — 
                 — 
                 4.1 
               
               
                   
                 Q96JH7_C219 
                 — 
                 — 
                 — 
                 — 
               
               
                   
                 P48200_C137 
                 1.6 
                 — 
                 — 
                 — 
               
               
                   
                 O00622_C39 
                 — 
                 2.0 
                 — 
                 — 
               
               
                   
                 Q5T1V6_C453 
                 — 
                 2.1 
                 — 
                 — 
               
               
                   
                 P51617_C608 
                 — 
                 — 
                 — 
                 — 
               
               
                   
                 P42575_C370 
                 2.0 
                 — 
                 1.2 
                 — 
               
               
                   
                 P09086_C346 
                 — 
                 — 
                 — 
                 — 
               
               
                   
                 Q09472_C1738 
                 — 
                 1.5 
                 — 
                 — 
               
               
                   
                 Q01201_C109 
                 — 
                 — 
                 — 
                 — 
               
               
                   
                 Q70CQ2_C1741 
                 — 
                 — 
                 — 
                 — 
               
               
                   
                 P41226_C599 
                 — 
                 — 
                 — 
                 — 
               
               
                   
                 P14598_C378 
                 1.3 
                 — 
                 — 
                 — 
               
               
                   
                 Q9C0C9_C375 
                 — 
                 — 
                 — 
                 — 
               
               
                   
                 O00622_C134 
                 — 
                 1.7 
                 — 
                 20.0  
               
               
                   
                 O00541_C361 
                 — 
                 20.0  
                 — 
                 — 
               
               
                   
                 P43403_C117 
                 — 
                 — 
                 — 
                 20.0  
               
               
                   
                 Q96FA3_C282 
                 — 
                 — 
                 — 
                 — 
               
               
                   
                 Q9UPT9_C44 
                 1.5 
                 — 
                 — 
                 — 
               
               
                   
                 Q9Y4C1_C251 
                 — 
                 — 
                 — 
                 — 
               
               
                   
                 Q70EQ2_C1090 
                 — 
                 — 
                 — 
                 — 
               
               
                   
                 O00622_C70 
                 — 
                 — 
                 — 
                 — 
               
               
                   
                 P04150_C622 
                 — 
                 — 
                 — 
                 — 
               
               
                   
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
               
             
               
                 TABLE 1C 
               
               
                   
               
             
            
               
                   
                 10_500μM —   
                 11_500μM —   
                 11_500μM —   
                 12_500μM —   
                 12_500μM —   
               
               
                 Identifier 
                 invitro_ramos 
                 invitro_231 
                 invitro_ramos 
                 invitro_231 
                 invitro_ramos 
               
               
                   
               
               
                 Q99873_C109 
                 1.3 
                 20.0  
                 20.0  
                 1.4 
                 1.3 
               
               
                 P24752_C119 
                 1.4 
                 1.2 
                 0.9 
                 1.0 
                 0.7 
               
               
                 P09211_C48 
                 0.8 
                 1.7 
                 1.1 
                 2.9 
                 1.1 
               
               
                 O14980_C34 
                 0.7 
                 1.2 
                 1.0 
                 1.2 
                 0.7 
               
               
                 P24752_C196 
                 1.7 
                 1.5 
                 1.3 
                 1.2 
                 0.9 
               
               
                 Q15084_C55 
                 — 
                 20.0  
                 20.0  
                 3.7 
                 3.1 
               
               
                 P24752_C413 
                 1.6 
                 1.9 
                 1.7 
                 1.5 
                 1.1 
               
               
                 P63244_C182 
                 1.1 
                 1.0 
                 1.1 
                 0.9 
                 0.8 
               
               
                 P24752_C126 
                 1.5 
                 1.5 
                 — 
                 1.0 
                 1.1 
               
               
                 Q15084_C190 
                 3.3 
                 20.0  
                 20.0  
                 — 
                 20.0  
               
               
                 Q8TAQ2_C145 
                 — 
                 20.0  
                 — 
                 2.8 
                 1.6 
               
               
                 P68036_C86 
                 0.4 
                 — 
                 1.0 
                 — 
                 — 
               
               
                 P15374_C95 
                 — 
                 0.8 
                 0.8 
                 — 
                 0.5 
               
               
                 Q16763_C118 
                 — 
                 — 
                 — 
                 — 
                 0.6 
               
               
                 Q16822_C306 
                 1.1 
                 3.2 
                 1.2 
                 1.5 
                 0.7 
               
               
                 O14980_C528 
                 — 
                 1.0 
                 0.7 
                 1.1 
                 — 
               
               
                 O00170_C122 
                 1.7 
                 — 
                 2.8 
                 — 
                 1.3 
               
               
                 O75874_C269 
                 — 
                 1.1 
                 0.7 
                 — 
                 — 
               
               
                 O75362_C286 
                 — 
                 1.2 
                 1.2 
                 1.0 
                 — 
               
               
                 P40763_C259 
                 — 
                 20.0  
                 20.0  
                 — 
                 — 
               
               
                 Q9Y3Z3_C522 
                 — 
                 2.1 
                 — 
                 — 
                 — 
               
               
                 P16455_C150 
                 20.0  
                 — 
                 20.0  
                 — 
                 20.0  
               
               
                 Q96GG9_C115 
                 1.0 
                 — 
                 0.9 
                 — 
                 0.6 
               
               
                 P00813_C75 
                 1.0 
                 — 
                 7.5 
                 — 
                 0.7 
               
               
                 O14933_C98 
                 — 
                 — 
                 3.4 
                 — 
                 1.3 
               
               
                 Q14790_C360 
                 1.5 
                 20.0  
                 20.0  
                 — 
               
               
                 Q15306_C194 
                 2.5 
                 — 
                 4.3 
                 — 
                 3.7 
               
               
                 Q6L8Q7_C108 
                 — 
                 4.2 
                 — 
                 — 
                 1.5 
               
               
                 P48735_C308 
                 — 
                 1.1 
                 — 
                 1.7 
                 — 
               
               
                 Q86UV5_C39 
                 — 
                 — 
                 1.0 
                 — 
                 — 
               
               
                 P50851_C1704 
                 0.8 
                 — 
                 1.4 
                 — 
                 — 
               
               
                 O94953_C694 
                 1.4 
                 — 
                 1.9 
                 — 
                 — 
               
               
                 P19447_C342 
                 — 
                 2.9 
                 1.5 
                 3.0 
                 — 
               
               
                 Q00535_C157 
                 — 
                 — 
                 1.3 
                 — 
                 1.0 
               
               
                 Q9UPT9_C171 
                 3.8 
                 — 
                 8.2 
                 — 
                 4.1 
               
               
                 Q9HB90_C377 
                 — 
                 — 
                 1.6 
                 — 
                 — 
               
               
                 P50851_C2675 
                 1.3 
                 — 
                 1.3 
                 — 
                 1.5 
               
               
                 Q9NYL2_C22 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q5T1V6_C414 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q9HB90_C358 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 P16455_C145 
                 — 
                 — 
                 20.0  
                 — 
                 — 
               
               
                 Q9Y5T5_C205 
                 — 
                 20.0  
                 — 
                 2.2 
                 — 
               
               
                 O00541_C272 
                 2.2 
                 — 
                 4.2 
                 — 
                 — 
               
               
                 Q02556_C306 
                 3.6 
                 — 
                 3.1 
                 — 
                 — 
               
               
                 Q15910_C503 
                 — 
                 — 
                 1.3 
                 — 
                 — 
               
               
                 Q96RU2_C171 
                 — 
                 20.0  
                 — 
                 — 
                 — 
               
               
                 Q16877_C159 
                 — 
                 — 
                 0.6 
                 — 
                 — 
               
               
                 P04150_C302 
                 — 
                 — 
                 1.5 
                 — 
                 1.3 
               
               
                 Q96JH7_C219 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 P48200_C137 
                 2.1 
                 — 
                 3.7 
                 — 
                 — 
               
               
                 O00622_C39 
                 — 
                 9.6 
                 — 
                 — 
                 — 
               
               
                 Q5T1V6_C453 
                 — 
                 20.0  
                 — 
                 — 
                 — 
               
               
                 P51617_C608 
                 — 
                 — 
                 1.3 
                 — 
                 — 
               
               
                 P42575_C370 
                 1.2 
                 — 
                 6.0 
                 — 
                 — 
               
               
                 P09086_C346 
                 — 
                 — 
                 1.7 
                 — 
                 — 
               
               
                 Q09472_C1738 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q01201_C109 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q70CQ2_C741 
                 0.9 
                 — 
                 — 
                 — 
                 — 
               
               
                 P41226_C599 
                 — 
                 — 
                 1.9 
                 — 
                 — 
               
               
                 P14598_C378 
                 1.1 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q9C0C9_C375 
                 0.8 
                 — 
                 — 
                 — 
                 — 
               
               
                 O00622_C134 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 O00541_C361 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 P43403_C117 
                 20.0  
                 — 
                 — 
                 — 
                 — 
               
               
                 Q96FA3_C282 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q9UPT9_C44 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q9Y4C1_C251 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q70CQ2_C1090 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 O00622_C70 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 P04150_C622 
                 — 
                 1.7 
                 — 
                 — 
                 — 
               
               
                   
               
               
                   
                 13_500μM —   
                 13_500μM —   
                 14_500μM —   
                 14_500μM —   
                 15_500μM —   
               
               
                 Identifier 
                 invitro_231 
                 invitro_ramos 
                 invito_231 
                 invitro_ramos 
                 invito_231 
               
               
                   
               
               
                 Q99873_C109 
                 1.0 
                 0.9 
                 0.8 
                 1.4 
                 0.9 
               
               
                 P24752_C119 
                 1.2 
                 0.6 
                 1.2 
                 1.8 
                 1.0 
               
               
                 P09211_C48 
                 1.5 
                 1.2 
                 3.2 
                 2.1 
                 2.5 
               
               
                 O14980_C34 
                 0.9 
                 0.7 
                 1.1 
                 1.5 
                 — 
               
               
                 P24752_C196 
                 1.6 
                 1.7 
                 1.1 
                 1.4 
                 0.9 
               
               
                 Q15084_C55 
                 1.9 
                 1.1 
                 1.0 
                 1.4 
                 0.8 
               
               
                 P24752_C413 
                 5.5 
                 7.3 
                 1.3 
                 1.6 
                 1.2 
               
               
                 P63244_C182 
                 1.4 
                 0.8 
                 1.2 
                 1.5 
                 — 
               
               
                 P24752_C126 
                 9.6 
                 20.0  
                 1.1 
                 1.4 
                 0.8 
               
               
                 Q15084_C190 
                 1.5 
                 1.3 
                 1.1 
                 1.8 
                 0.9 
               
               
                 Q8TAQ2_C145 
                 — 
                 0.8 
                 1.1 
                 2.3 
                 — 
               
               
                 P68036_C86 
                 1.1 
                 0.8 
                 1.0 
                 1.1 
                 — 
               
               
                 P15374_C95 
                 — 
                 0.8 
                 1.2 
                 1.0 
                 — 
               
               
                 Q16763_C118 
                 — 
                 0.7 
                 0.7 
                 1.2 
                 — 
               
               
                 Q16822_C306 
                 0.9 
                 1.0 
                 — 
                 20.0  
                 — 
               
               
                 O14980_C528 
                 — 
                 0.5 
                 20.0  
                 20.0  
                 0.8 
               
               
                 O00170_C122 
                 — 
                 0.9 
                 — 
                 2.5 
                 — 
               
               
                 O75874_C269 
                 2.7 
                 — 
                 0.9 
                 1.3 
                 — 
               
               
                 O75362_C286 
                 0.9 
                 0.9 
                 0.9 
                 — 
                 — 
               
               
                 P40763_C259 
                 — 
                 1.2 
                 0.8 
                 3.1 
                 — 
               
               
                 Q9Y3Z3_C522 
                 0.8 
                 — 
                 1.7 
                 1.5 
                 — 
               
               
                 P16455_C150 
                 — 
                 4.2 
                 5.5 
                 5.1 
                 — 
               
               
                 Q96GG9_C115 
                 — 
                 — 
                 1.1 
                 1.6 
                 — 
               
               
                 P00813_C75 
                 — 
                 0.9 
                 1.5 
                 1.7 
                 — 
               
               
                 O14933_C98 
                 — 
                 1.0 
                 — 
                 2.8 
                 — 
               
               
                 Q14790_C360 
                 — 
                 — 
                 1.4 
                 1.9 
                 — 
               
               
                 Q15306_C194 
                 — 
                 1.1 
                 1.3 
                 2.2 
                 — 
               
               
                 Q6L8Q7_C108 
                 — 
                 1.0 
                 0.5 
                 2.2 
                 1.1 
               
               
                 P48735_C308 
                 1.1 
                 — 
                 4.7 
                 — 
                 — 
               
               
                 Q86UV5_C39 
                 0.8 
                 0.6 
                 0.8 
                 — 
                 — 
               
               
                 P50851_C1704 
                 0.7 
                 0.8 
                 1.9 
                 1.7 
                 — 
               
               
                 O94953_C694 
                 1.4 
                 1.1 
                 — 
                 2.0 
                 — 
               
               
                 P19447_C342 
                 1.0 
                 — 
                 4.7 
                 — 
                 — 
               
               
                 Q00535_C157 
                 — 
                 — 
                 6.1 
                 2.3 
                 — 
               
               
                 Q9UPT9_C171 
                 — 
                 0.8 
                 4.0 
                 4.0 
                 — 
               
               
                 Q9HB90_C377 
                 2.1 
                 — 
                 — 
                 20.0  
                 — 
               
               
                 P50851_C2675 
                 — 
                 — 
                 1.9 
                 2.9 
                 — 
               
               
                 Q9NYL2_C22 
                 5.2 
                 — 
                 1.6 
                 — 
                 — 
               
               
                 Q5T1V6_C414 
                 — 
                 1.2 
                 — 
                 4.0 
                 — 
               
               
                 Q9HB90_C358 
                 1.5 
                 — 
                 0.9 
                 2.1 
                 1.1 
               
               
                 P16455_C145 
                 — 
                 20.0  
                 1.5 
                 2.0 
                 — 
               
               
                 Q9Y5T5_C205 
                 — 
                 3.3 
                   
                 — 
                 — 
               
               
                 O00541_C272 
                 1.7 
                 — 
                 2.6 
                 — 
                 — 
               
               
                 Q02556_C306 
                 — 
                 0.7 
                 2.4 
                 2.3 
                 — 
               
               
                 Q15910_C503 
                 — 
                 0.8 
                 0.6 
                 1.9 
                 0.8 
               
               
                 Q96RU2_C171 
                 — 
                 2.4 
                 1.0 
                 — 
                 — 
               
               
                 Q16877_C159 
                 0.9 
                 — 
                 2.3 
                 — 
                 — 
               
               
                 P04150_C302 
                 — 
                 — 
                 — 
                 2.2 
                 — 
               
               
                 Q96JH7_C219 
                 — 
                 — 
                 0.6 
                 1.5 
                 — 
               
               
                 P48200_C137 
                 — 
                 — 
                 5.2 
                 — 
                 — 
               
               
                 O00622_C39 
                 1.2 
                 — 
                 3.6 
                 — 
                 — 
               
               
                 Q5T1V6_C453 
                 — 
                 1.4 
                 2.2 
                 — 
                 — 
               
               
                 P51617_C608 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 P42575_C370 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 P09086_C346 
                 — 
                 0.6 
                 — 
                 — 
                 — 
               
               
                 Q09472_C1738 
                 — 
                 0.7 
                 2.1 
                 — 
                 — 
               
               
                 Q01201_C109 
                 — 
                 — 
                 1.7 
                 2.4 
                 — 
               
               
                 Q70CQ2_C741 
                 0.8 
                 — 
                 — 
                 — 
                 — 
               
               
                 P41226_C599 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 P14598_C378 
                 — 
                 0.7 
                 — 
                 — 
                 — 
               
               
                 Q9C0C9_C375 
                 — 
                 — 
                 2.8 
                 — 
                 — 
               
               
                 O00622_C134 
                 — 
                 — 
                 0.7 
                 — 
                 — 
               
               
                 O00541_C361 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 P43403_C117 
                 — 
                 — 
                 — 
                 1.3 
                 — 
               
               
                 Q96FA3_C282 
                 — 
                 — 
                 1.4 
                 — 
                 — 
               
               
                 Q9UPT9_C44 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q9Y4C1_C251 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q70CQ2_C1090 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 O00622_C70 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 P04150_C622 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
               
             
               
                 TABLE 1D 
               
               
                   
               
             
            
               
                   
                 15_500μM —   
                 27_500μM —   
                 20_500μM —   
                 20_500μM —   
                 21_500μM —   
               
               
                 Identifier 
                 invitro_ramos 
                 invitro_231 
                 invitro_231 
                 invitro_ramos 
                 invitro_231 
               
               
                   
               
               
                 Q99873_C109 
                 1.2 
                 0.7 
                 1.9 
                 2.2 
                 1.1 
               
               
                 P24752_C119 
                 1.2 
                 0.9 
                 3.6 
                 2.6 
                 0.9 
               
               
                 P09211_C48 
                 1.3 
                 1.3 
                 2.5 
                 1.1 
                 1.1 
               
               
                 O14980_C34 
                 1.2 
                 0.9 
                 1.0 
                 1.2 
                 0.9 
               
               
                 P24752_C196 
                 1.6 
                 0.9 
                 3.7 
                 2.9 
                 1.0 
               
               
                 Q15084_C55 
                 1.0 
                 0.8 
                 1.7 
                 2.0 
                 1.1 
               
               
                 P24752_C413 
                 0.9 
                 0.9 
                 20.0  
                 14.0  
                 1.4 
               
               
                 P63244_C182 
                 1.3 
                 1.0 
                 1.4 
                 1.1 
                 0.9 
               
               
                 P24752_C126 
                 — 
                 0.9 
                 10.6  
                 20.0  
                 1.2 
               
               
                 Q15084_C190 
                 1.2 
                 0.9 
                 2.1 
                 2.1 
                 1.1 
               
               
                 Q8TAQ2_C145 
                 1.2 
                 0.9 
                 2.9 
                 3.9 
                 1.2 
               
               
                 P68036_C86 
                 1.3 
                 1.2 
                 1.1 
                 1.2 
                 1.2 
               
               
                 P15374_C95 
                 0.7 
                 0.4 
                 1.0 
                 0.9 
                 1.1 
               
               
                 Q16763_C118 
                 1.2 
                 0.8 
                 — 
                 2.9 
                 0.9 
               
               
                 Q16822_C306 
                 — 
                 1.4 
                 2.5 
                 1.6 
                 1.2 
               
               
                 O14980_C528 
                 1.0 
                 1.2 
                 1.4 
                 4.0 
                 0.9 
               
               
                 O00170_C122 
                 1.4 
                 0.4 
                 — 
                 2.2 
                 1.4 
               
               
                 O75874_C269 
                 0.6 
                 0.4 
                 — 
                 0.6 
                 1.5 
               
               
                 O75362_C286 
                 — 
                 20.0  
                 1.3 
                 — 
                 0.9 
               
               
                 P40763_C259 
                 1.9 
                 0.7 
                 — 
                 3.0 
                 — 
               
               
                 Q9Y3Z3_C522 
                 1.6 
                 0.8 
                 2.1 
                 1.3 
                 — 
               
               
                 P16455_C150 
                 1.9 
                 1.0 
                 — 
                 18.3  
                 — 
               
               
                 Q96GG9_C115 
                 0.8 
                 1.1 
                 1.2 
                 1.2 
                 1.0 
               
               
                 P00813_C75 
                 1.1 
                 1.1 
                 — 
                 1.5 
                 — 
               
               
                 O14933_C98 
                 1.3 
                 1.2 
                 — 
                 3.9 
                 — 
               
               
                 Q14790_C360 
                 — 
                 0.8 
                 1.9 
                 1.5 
                 1.9 
               
               
                 Q15306_C194 
                 2.2 
                 — 
                 — 
                 3.0 
                 — 
               
               
                 Q6L8Q7_C108 
                 — 
                 0.5 
                 1.6 
                 — 
                 — 
               
               
                 P48735_C308 
                 — 
                 1.9 
                 0.5 
                 — 
                 0.6 
               
               
                 Q86UV5_C39 
                 0.7 
                 0.8 
                 1.1 
                 1.8 
                 20.0  
               
               
                 P50851_C1704 
                 1.9 
                 — 
                 2.0 
                 1.7 
                 — 
               
               
                 O94953_C694 
                 1.1 
                 1.4 
                 2.8 
                 2.0 
                 — 
               
               
                 P19447_C342 
                 — 
                 0.8 
                 2.6 
                 — 
                 6.1 
               
               
                 Q00535_C157 
                 — 
                 — 
                 — 
                 2.0 
                 — 
               
               
                 Q9UPT9_C171 
                 — 
                 — 
                 — 
                 20.0  
                 — 
               
               
                 Q9HB90_C377 
                 — 
                 1.0 
                 — 
                 — 
                 1.4 
               
               
                 P50851_C2675 
                 1.6 
                 — 
                 — 
                 — 
                 0.9 
               
               
                 Q9NYL2_C22 
                 — 
                 1.1 
                 20.0  
                 — 
                 2.0 
               
               
                 Q5T1V6_C414 
                 1.0 
                 0.8 
                 — 
                 3.1 
                 1.2 
               
               
                 Q9HB90_C358 
                 — 
                 0.3 
                 — 
                 — 
                 1.2 
               
               
                 P16455_C145 
                 1.3 
                 — 
                 — 
                 20.0  
                 — 
               
               
                 Q9Y5T5_C205 
                 — 
                 1.6 
                 — 
                 — 
                 1.6 
               
               
                 O00541_C272 
                 — 
                 1.1 
                 — 
                 — 
                 — 
               
               
                 Q02556_C306 
                 2.1 
                 — 
                 — 
                 2.1 
                 — 
               
               
                 Q15910_C503 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q96RU2_C171 
                 — 
                 0.9 
                 — 
                 2.4 
                 1.1 
               
               
                 Q16877_C159 
                 — 
                 — 
                 — 
                 1.0 
                 — 
               
               
                 P04150_C302 
                 0.9 
                 1.3 
                 — 
                 — 
                 — 
               
               
                 Q96JH7_C219 
                 1.3 
                 1.7 
                 — 
                 1.2 
                 — 
               
               
                 P48200_C137 
                 2.0 
                 1.4 
                 — 
                 5.2 
                 — 
               
               
                 O00622_C39 
                 — 
                 1.0 
                 — 
                 — 
                 — 
               
               
                 Q5T1V6_C453 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 P51617_C608 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 P42575_C370 
                 — 
                 0.9 
                 — 
                 — 
                 — 
               
               
                 P09086_C346 
                 0.8 
                 — 
                 — 
                 2.3 
                 0.9 
               
               
                 Q09472_C1738 
                 — 
                 — 
                 — 
                 3.2 
                 — 
               
               
                 Q01201_C109 
                 — 
                 0.8 
                 — 
                 — 
                 — 
               
               
                 Q70CQ2_C741 
                 — 
                 — 
                 2.8 
                 1.7 
                 — 
               
               
                 P41226_C599 
                 — 
                 0.7 
                 1.1 
                 12.2  
                 — 
               
               
                 P14598_C378 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q9C0C9_C375 
                 — 
                 0.7 
                 — 
                 — 
                 — 
               
               
                 O00622_C134 
                 — 
                 1.5 
                 20.0  
                 — 
                 — 
               
               
                 O00541_C361 
                 — 
                 0.6 
                 20.0  
                 20.0  
                 — 
               
               
                 P43403_C117 
                 20.0  
                 — 
                 — 
                 20.0  
                 — 
               
               
                 Q96FA3_C282 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q9UPT9_C44 
                 — 
                 20.0  
                 — 
                 — 
                 — 
               
               
                 Q9Y4C1_C251 
                 — 
                 — 
                 — 
                 — 
                 0.7 
               
               
                 Q70CQ2_C1090 
                 — 
                 — 
                 — 
                 2.7 
                 — 
               
               
                 O00622_C70 
                 — 
                 1.1 
                 — 
                 — 
                 — 
               
               
                 P04150_C622 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                   
               
               
                   
                 21_500μM —   
                 22_500μM —   
                 22_500μM —   
                 23_500μM —   
                 23_500μM —   
               
               
                 Identifier 
                 invitro_ramos 
                 invitro_231 
                 invitro_ramos 
                 invitro_231 
                 invitro_ramos 
               
               
                   
               
               
                 Q99873_C109 
                 1.5 
                 1.0 
                 1.0 
                 0.8 
                 1.0 
               
               
                 P24752_C119 
                 1.1 
                 1.0 
                 0.8 
                 1.7 
                 2.0 
               
               
                 P09211_C48 
                 1.3 
                 0.9 
                 0.7 
                 0.8 
                 0.9 
               
               
                 O14980_C34 
                 1.2 
                 1.1 
                 — 
                 3.4 
                 5.3 
               
               
                 P24752_C196 
                 1.1 
                 1.4 
                 0.7 
                 — 
                 1.8 
               
               
                 Q15084_C55 
                 2.1 
                 2.1 
                 1.6 
                 0.8 
                 1.0 
               
               
                 P24752_C413 
                 1.4 
                 1.1 
                 1.1 
                 1.1 
                 1.2 
               
               
                 P63244_C182 
                 0.9 
                 1.6 
                 — 
                 4.6 
                 — 
               
               
                 P24752_C126 
                 1.4 
                 2.4 
                 1.7 
                 0.8 
                 0.8 
               
               
                 Q15084_C190 
                 2.3 
                 2.2 
                 4.2 
                 0.8 
                 1.1 
               
               
                 Q8TAQ2_C145 
                 — 
                 — 
                 1.2 
                 1.3 
                 — 
               
               
                 P68036_C86 
                 2.0 
                 — 
                 0.8 
                 7.4 
                 13.2  
               
               
                 P15374_C95 
                 — 
                 — 
                 0.7 
                 0.8 
                 1.1 
               
               
                 Q16763_C118 
                 — 
                 — 
                 0.9 
                 1.6 
                 2.4 
               
               
                 Q16822_C306 
                 2.0 
                 — 
                 — 
                 3.0 
                 — 
               
               
                 014980_C528 
                 0.8 
                 — 
                 — 
                 — 
                 2.9 
               
               
                 000170_C122 
                 — 
                 1.3 
                 1.1 
                 0.7 
                 1.4 
               
               
                 075874_C269 
                 — 
                 1.0 
                 — 
                 0.7 
                 1.1 
               
               
                 075362_C286 
                 — 
                 — 
                 — 
                 20.0  
                 — 
               
               
                 P40763_C259 
                 2.9 
                 2.0 
                 — 
                 1.1 
                 0.8 
               
               
                 Q9Y3Z3_C522 
                 1.4 
                 — 
                 0.8 
                 — 
                 — 
               
               
                 P16455_C150 
                 17.2  
                 — 
                 2.9 
                 — 
                 1.0 
               
               
                 Q96GG9_C115 
                 1.0 
                 1.0 
                 0.8 
                 — 
                 20.0  
               
               
                 POOS13_C75 
                 1.3 
                 — 
                 1.3 
                 — 
                 1.1 
               
               
                 O14933_C98 
                 — 
                 — 
                 2.0 
                 0.7 
                 1.2 
               
               
                 Q14790_C360 
                 1.9 
                 — 
                 — 
                 1.4 
                 1.4 
               
               
                 Q15306_C194 
                 1.7 
                 — 
                 1.1 
                 — 
                 1.9 
               
               
                 Q6L8Q7_C108 
                 — 
                 — 
                 — 
                 1.0 
                 — 
               
               
                 P48735_C308 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q86UV5_C39 
                 1.2 
                 — 
                 — 
                 — 
                 1.3 
               
               
                 P50851_C1704 
                 1.6 
                 — 
                 — 
                 — 
                 3.4 
               
               
                 094953_C694 
                 1.8 
                 — 
                 — 
                 — 
                 3.2 
               
               
                 P19447_C342 
                 — 
                 — 
                 — 
                 1.6 
                 — 
               
               
                 Q00535_C157 
                 — 
                 — 
                 0.9 
                 — 
                 2.8 
               
               
                 Q9UPT9_C171 
                 — 
                 — 
                 1.1 
                 — 
                 5.1 
               
               
                 Q9HB90_C377 
                 — 
                 1.7 
                 0.9 
                 1.5 
                 — 
               
               
                 P50851_C2675 
                 1.5 
                 1.1 
                 1.1 
                 — 
                 2.6 
               
               
                 Q9NYL_2 C22 
                 — 
                 1.0 
                 — 
                 1.4 
                 — 
               
               
                 Q5T1V6_C414 
                 — 
                 — 
                 1.3 
                 — 
                 1.4 
               
               
                 Q9HB90_C358 
                 — 
                 1.7 
                 — 
                 — 
                 — 
               
               
                 P16455_C145 
                 — 
                 — 
                 — 
                 — 
                 1.0 
               
               
                 Q9Y5T5_C205 
                 — 
                 — 
                 1.6 
                 — 
                 1.2 
               
               
                 O00541_C272 
                 5.5 
                 1.6 
                 — 
                 — 
                 2.0 
               
               
                 Q02556_C306 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q15910_C503 
                 — 
                 — 
                 — 
                 — 
                 2.0 
               
               
                 Q96RU2_C171 
                 — 
                 — 
                 — 
                 — 
                 1.2 
               
               
                 Q16877_C159 
                 1.2 
                 — 
                 — 
                 — 
                 1.0 
               
               
                 P04150_C302 
                 — 
                 — 
                 0.9 
                 — 
                 4.7 
               
               
                 Q96JH7_C219 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 P48200_C137 
                 — 
                 — 
                 — 
                 — 
                 1.6 
               
               
                 O00622_C39 
                 — 
                 — 
                 — 
                 4.4 
                 — 
               
               
                 Q5T1V6_C453 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 P51617_C608 
                 — 
                 — 
                 — 
                 — 
                 1.5 
               
               
                 P42575_C370 
                 — 
                 — 
                 — 
                 — 
                 2.1 
               
               
                 P09086_C346 
                 — 
                 — 
                 — 
                 — 
                 1.1 
               
               
                 Q09472_C1738 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q01201_C109 
                 — 
                 — 
                 — 
                 — 
                 1.3 
               
               
                 Q70CQ2_C741 
                 1.7 
                 — 
                 — 
                 — 
                 — 
               
               
                 P41226_C599 
                 2.5 
                 — 
                 — 
                 — 
                 3.2 
               
               
                 P14598_C378 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q9C0C9_C375 
                 2.4 
                 — 
                 — 
                 — 
                 1.4 
               
               
                 O00622_C134 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 O00541_C361 
                 — 
                 — 
                 — 
                 — 
                 1.1 
               
               
                 P43403_C117 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q96FA3_C282 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q9UPT9_C44 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q9Y4C1_C251 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q70CQ2_C1090 
                 0.9 
                 — 
                 — 
                 — 
                 — 
               
               
                 O00622_C70 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 P04150_C622 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
               
             
               
                 TABLE 1E 
               
               
                   
               
             
            
               
                   
                 24_500μM —   
                 25_500μM —   
                 26_500μM —   
                 27_500μM —   
                 27_500μM —   
               
               
                 Identifier 
                 invitro_ramos 
                 invitro_231 
                 invitro_ramos 
                 invitro_231 
                 invitro_ramos 
               
               
                   
               
               
                 Q99873_C109 
                 1.0 
                 1.0 
                 0.9 
                 0.9 
                 1.0 
               
               
                 P24752_C119 
                 1.3 
                 1.0 
                 1.0 
                 1.0 
                 1.0 
               
               
                 P09211_C48 
                 1.6 
                 1.8 
                 0.9 
                 1.0 
                 1.0 
               
               
                 O14980_C34 
                 1.1 
                 0.9 
                 0.9 
                 1.0 
                 1.0 
               
               
                 P24752_C196 
                 1.1 
                 0.9 
                 1.0 
                 1.0 
                 1.1 
               
               
                 Q15084_C55 
                 1.3 
                 1.0 
                 0.9 
                 1.1 
                 1.2 
               
               
                 P24752_C413 
                 1.2 
                 1.0 
                 0.9 
                 1.1 
                 1.3 
               
               
                 P63244_C182 
                 2.6 
                 1.2 
                 1.0 
                 0.8 
                 1.1 
               
               
                 P24752_C126 
                 1.1 
                 0.9 
                 0.9 
                 1.0 
                 1.3 
               
               
                 Q15084_C190 
                 1.7 
                 1.0 
                 0.9 
                 — 
                 1.1 
               
               
                 Q8TAQ2_C145 
                 5.4 
                 0.9 
                 0.9 
                 — 
                 1.2 
               
               
                 P68036_C86 
                 — 
                 1.5 
                 0.7 
                 0.9 
                 — 
               
               
                 P15374_C95 
                 1.1 
                 0.8 
                 0.8 
                 — 
                 1.0 
               
               
                 Q16763_C118 
                 1.2 
                 1.0 
                 0.9 
                 — 
                 0.9 
               
               
                 Q16822_C306 
                 — 
                 0.8 
                 — 
                 1.5 
                 1.1 
               
               
                 O14980_C528 
                 20.0  
                 — 
                 0.9 
                 0.9 
                 0.8 
               
               
                 O00170_C122 
                 1.3 
                 — 
                 0.9 
                 — 
                 1.0 
               
               
                 O75874_C269 
                 0.9 
                 1.0 
                 — 
                 1.0 
                 — 
               
               
                 O75362_C286 
                 — 
                 20.0  
                 — 
                 0.9 
                 1.0 
               
               
                 P40763_C259 
                 1.7 
                 0.9 
                 — 
                 — 
                 — 
               
               
                 Q9Y3Z3_C522 
                 1.1 
                 — 
                 0.9 
                 1.0 
                 0.9 
               
               
                 P16455_C150 
                 4.0 
                 — 
                 0.9 
                 — 
                 2.3 
               
               
                 Q96GG9_C115 
                 1.7 
                 — 
                 0.9 
                 — 
                 1.0 
               
               
                 P00813_C75 
                 1.2 
                 — 
                 0.8 
                 — 
                 1.0 
               
               
                 O14933_C98 
                 — 
                 — 
                 1.0 
                 — 
                 1.0 
               
               
                 Q14790_C360 
                 1.4 
                 1.0 
                 — 
                 — 
                 1.2 
               
               
                 Q15306_C194 
                 1.9 
                 — 
                 1.1 
                 — 
                 1.0 
               
               
                 Q6L8Q7_C108 
                 1.4 
                 0.8 
                 1.1 
                 — 
                 1.3 
               
               
                 P48735_C308 
                 — 
                 14.5  
                 — 
                 1.0 
                 — 
               
               
                 Q86UV5_C39 
                 1.0 
                 1.0 
                 — 
                 — 
                 — 
               
               
                 P50851_C1704 
                 1.3 
                 0.8 
                 — 
                 1.1 
                 — 
               
               
                 O94953_C694 
                 — 
                 — 
                 — 
                 1.0 
                 — 
               
               
                 P19447_C342 
                 — 
                 0.9 
                 — 
                 1.1 
                 — 
               
               
                 Q00535_C157 
                 — 
                 — 
                 0.9 
                 — 
                 1.0 
               
               
                 Q9UPT9_C171 
                 3.1 
                 1.1 
                 1.0 
                 — 
                 1.2 
               
               
                 Q9HB90_C377 
                 1.5 
                 1.0 
                 — 
                 — 
                 — 
               
               
                 P50851_C2675 
                 1.0 
                 — 
                 0.9 
                 — 
                 — 
               
               
                 Q9NYL2_C22 
                 — 
                 0.8 
                 — 
                 — 
                 — 
               
               
                 Q5T1V6_C414 
                 1.7 
                 — 
                 — 
                 — 
                 1.0 
               
               
                 Q9HB90_C358 
                 0.9 
                 0.9 
                 — 
                 — 
                 — 
               
               
                 P16455_C145 
                 20.0  
                 — 
                 — 
                 — 
                 20.0  
               
               
                 Q9Y5T5_C205 
                 — 
                 — 
                 — 
                 — 
                 0.9 
               
               
                 O00541_C272 
                 2.6 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q02556_C306 
                 1.2 
                 — 
                 — 
                 — 
                 1.1 
               
               
                 Q15910_C503 
                 1.3 
                 0.8 
                 — 
                 — 
                 — 
               
               
                 Q96RU2_C171 
                 — 
                 — 
                 — 
                 1.2 
                 — 
               
               
                 Q16877_C159 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 P04150_C302 
                 — 
                 — 
                 — 
                 1.0 
                 — 
               
               
                 Q96JH7_C219 
                 1.2 
                 — 
                 — 
                 — 
                 — 
               
               
                 P48200_C137 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 O00622_C39 
                 — 
                 1.0 
                 — 
                 — 
                 — 
               
               
                 Q5T1V6_C453 
                 1.7 
                 0.9 
                 — 
                 1.0 
                 — 
               
               
                 P51617_C608 
                 1.3 
                 — 
                 — 
                 — 
                 — 
               
               
                 P42575_C370 
                 2.2 
                 — 
                 — 
                 — 
                 — 
               
               
                 P09086_C346 
                 1.1 
                 0.7 
                 — 
                 — 
                 — 
               
               
                 Q09472_C1738 
                 — 
                 1.6 
                 — 
                 1.0 
                 — 
               
               
                 Q01201_C109 
                 1.5 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q70CQ2_C741 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 P41226_C599 
                 — 
                 — 
                 — 
                 — 
                 1.3 
               
               
                 P14598_C378 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q9C0C9_C375 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 O00622_C134 
                 — 
                 1.0 
                 — 
                 — 
                 — 
               
               
                 O00541_C361 
                 — 
                 — 
                 — 
                 2.0 
                 — 
               
               
                 P43403_C117 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q96FA3_C282 
                 — 
                 — 
                 0.5 
                 — 
                 — 
               
               
                 Q9UPT9_C44 
                 — 
                 — 
                 — 
                 — 
                 1.2 
               
               
                 Q9Y4C1_C251 
                 1.3 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q70CQ2_C1090 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 O00622_C70 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 P04150_C622 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                   
               
               
                   
                 28_500μM —   
                 28_500μM —   
                 29_500μM —   
                 29_500μM —   
                 30_500μM —   
               
               
                 Identifier 
                 invitro_231 
                 invitro_ramos 
                 invitro_231 
                 invitro_ramos 
                 invitro_231 
               
               
                   
               
               
                 Q99873_C109 
                 0.8 
                 1.1 
                 1.0 
                 0.9 
                 1.1 
               
               
                 P24752_C119 
                 1.1 
                 1.1 
                 1.3 
                 0.6 
                 0.7 
               
               
                 P09211_C48 
                 1.3 
                 1.5 
                 1.0 
                 0.4 
                 1.4 
               
               
                 O14980_C34 
                 0.8 
                 0.9 
                 1.3 
                 0.9 
                 0.7 
               
               
                 P24752_C196 
                 1.0 
                 1.1 
                 1.3 
                 1.0 
                 0.8 
               
               
                 Q15084_C55 
                 1.1 
                 1.5 
                 1.0 
                 1.3 
                 2.2 
               
               
                 P24752_C413 
                 1.2 
                 1.4 
                 1.3 
                 0.7 
                 1.1 
               
               
                 P63244_C182 
                 1.0 
                 1.1 
                 1.3 
                 1.2 
                 1.2 
               
               
                 P24752_C126 
                 1.7 
                 1.6 
                 1.1 
                 0.8 
                 1.1 
               
               
                 Q15084_C190 
                 1.1 
                 1.6 
                 1.2 
                 — 
                 2.3 
               
               
                 Q8TAQ2_C145 
                 1.1 
                 1.2 
                 1.0 
                 — 
                 1.1 
               
               
                 P68036_C86 
                 1.4 
                 — 
                 0.9 
                 1.5 
                 — 
               
               
                 P15374_C95 
                 1.1 
                 0.9 
                 0.9 
                 1.0 
                 0.7 
               
               
                 Q16763_C118 
                 1.0 
                 0.8 
                 — 
                 — 
                 0.7 
               
               
                 Q16822_C306 
                 1.1 
                 — 
                 1.1 
                 0.5 
                 1.2 
               
               
                 O14980_C528 
                 — 
                 — 
                 1.0 
                 — 
                 — 
               
               
                 O00170_C122 
                 0.9 
                 1.2 
                 — 
                 1.3 
                 1.1 
               
               
                 O75874_C269 
                 1.1 
                 — 
                 0.8 
                 — 
                 0.7 
               
               
                 O75362_C286 
                 1.0 
                 1.0 
                 0.9 
                 — 
                 — 
               
               
                 P40763_C259 
                 1.0 
                 1.1 
                 1.5 
                 — 
                 — 
               
               
                 Q9Y3Z3_C522 
                 1.0 
                 — 
                 1.5 
                 — 
                 0.7 
               
               
                 P16455_C150 
                 — 
                 1.7 
                 — 
                 1.3 
                 — 
               
               
                 Q96GG9_C115 
                 — 
                 — 
                 — 
                 — 
                 0.7 
               
               
                 P00813_C75 
                 — 
                 0.9 
                 — 
                 — 
                 — 
               
               
                 O14933_C98 
                 — 
                 1.2 
                 — 
                 — 
                 1.3 
               
               
                 Q14790_C360 
                 1.1 
                 — 
                 — 
                 — 
                 2.0 
               
               
                 Q15306_C194 
                 — 
                 1.1 
                 — 
                 1.2 
                 — 
               
               
                 Q6L8Q7_C108 
                 1.0 
                 1.2 
                 — 
                 — 
                 1.1 
               
               
                 P48735_C308 
                 0.9 
                 — 
                 1.0 
                 — 
                 0.7 
               
               
                 Q86UV5_C39 
                 — 
                 — 
                 1.2 
                 — 
                 — 
               
               
                 P50851_C1704 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 O94953_C694 
                 — 
                 — 
                 1.2 
                 — 
                 — 
               
               
                 P19447_C342 
                 — 
                 — 
                 0.8 
                 — 
                 1.3 
               
               
                 Q00535_C157 
                 0.9 
                 1.0 
                 — 
                 — 
                 — 
               
               
                 Q9UPT9_C171 
                 — 
                 1.3 
                 — 
                 — 
                 — 
               
               
                 Q9HB90_C377 
                 1.3 
                 — 
                 1.3 
                 — 
                 1.4 
               
               
                 P50851_C2675 
                 — 
                 — 
                 1.1 
                 — 
                 0.9 
               
               
                 Q9NYL2_C22 
                 1.4 
                 — 
                 1.2 
                 — 
                 1.1 
               
               
                 Q5T1V6_C414 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q9HB90_C358 
                 1.1 
                 — 
                 — 
                 — 
                 1.0 
               
               
                 P16455_C145 
                 — 
                 20.0  
                 — 
                 20.0  
                 — 
               
               
                 Q9Y5T5_C205 
                 — 
                 1.6 
                 — 
                 — 
                 — 
               
               
                 O00541_C272 
                 — 
                 — 
                 0.9 
                 — 
                 — 
               
               
                 Q02556_C306 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q15910_C503 
                 — 
                 — 
                 1.4 
                 — 
                 — 
               
               
                 Q96RU2_C171 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q16877_C159 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 P04150_C302 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q96JH7_C219 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 P48200_C137 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 O00622_C39 
                 1.0 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q5T1V6_C453 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 P51617_C608 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 P42575_C370 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 P09086_C346 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q09472_C1738 
                 — 
                 — 
                 1.3 
                 — 
                 — 
               
               
                 Q01201_C109 
                 — 
                 1.1 
                 — 
                 — 
                 — 
               
               
                 Q70CQ2_C741 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 P41226_C599 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 P14598_C378 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q9C0C9_C375 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 O00622_C134 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 O00541_C361 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 P43403_C117 
                 — 
                 1.1 
                 — 
                 — 
                 — 
               
               
                 Q96FA3_C282 
                 — 
                 0.7 
                 — 
                 — 
                 — 
               
               
                 Q9UPT9_C44 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q9Y4C1_C251 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q70CQ2_C1090 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 O00622_C70 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 P04150_C622 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
               
             
               
                 TABLE 1F 
               
               
                   
               
             
            
               
                   
                 30_500μM —   
                 31_500μM —   
                 31_500μM —   
                 32_500μM —   
                 32_500μM —   
               
               
                 Identifier 
                 invitro_ramos 
                 invitro_231 
                 invitro_ramos 
                 invitro_231 
                 invitro_ramos 
               
               
                   
               
               
                 Q99873_C109 
                 1.8 
                 1.0 
                 1.3 
                 1.7 
                 1.8 
               
               
                 P24752_C119 
                 0.9 
                 1.3 
                 0.7 
                 1.7 
                 1.3 
               
               
                 P09211_C48 
                 1.2 
                 2.0 
                 1.3 
                 1.9 
                 1.4 
               
               
                 O14980_C34 
                 1.1 
                 1.0 
                 0.8 
                 1.2 
                 1.0 
               
               
                 P24752_C196 
                 1.1 
                 1.2 
                 0.9 
                 2.3 
                 2.0 
               
               
                 Q15084_C55 
                 — 
                 1.2 
                 1.1 
                 20.0  
                 20.0  
               
               
                 P24752_C413 
                 1.9 
                 1.6 
                 1.0 
                 6.8 
                 4.1 
               
               
                 P63244_C182 
                 1.6 
                 1.3 
                 — 
                 1.9 
                 — 
               
               
                 P24752_C126 
                 1.6 
                 1.1 
                 — 
                 7.3 
                 8.6 
               
               
                 Q15084_C190 
                 — 
                 1.3 
                 1.2 
                 20.0  
                 20.0  
               
               
                 Q8TAQ2_C145 
                 1.5 
                 1.1 
                 0.9 
                 20.0  
                 20.0  
               
               
                 P68036_C86 
                 1.5 
                 1.7 
                 1.3 
                 1.1 
                 0.9 
               
               
                 P15374_C95 
                 1.0 
                 0.9 
                 0.7 
                 1.2 
                 1.0 
               
               
                 Q16763_C118 
                 1.1 
                 0.9 
                 0.8 
                 1.1 
                 1.1 
               
               
                 Q16822_C306 
                 1.1 
                 1.9 
                 1.2 
                 3.2 
                 — 
               
               
                 O14980_C528 
                 — 
                 5.2 
                 3.2 
                 1.7 
                 1.2 
               
               
                 O00170_C122 
                 2.0 
                 — 
                 0.6 
                 3.7 
                 1.9 
               
               
                 O75874_C269 
                 — 
                 0.4 
                 0.7 
                 — 
                 — 
               
               
                 O75362_C286 
                 2.1 
                 — 
                 — 
                 — 
                 — 
               
               
                 P40763_C259 
                 — 
                 1.7 
                 — 
                 10.2  
                 — 
               
               
                 Q9Y3Z3_C522 
                 — 
                 1.5 
                 — 
                 — 
                 1.8 
               
               
                 P16455_C150 
                 5.1 
                 — 
                 2.8 
                 — 
                 20.0  
               
               
                 Q96GG9_C115 
                 1.1 
                 — 
                 0.9 
                 — 
                 0.9 
               
               
                 P00813_C75 
                 3.1 
                 — 
                 0.8 
                 — 
                 1.7 
               
               
                 O14933_C98 
                 2.1 
                 — 
                 — 
                 13.8  
                 4.6 
               
               
                 Q14790_C360 
                 5.2 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q15306_C194 
                 1.7 
                 — 
                 1.1 
                 — 
                 3.7 
               
               
                 Q6L8Q7_C108 
                 1.6 
                 2.0 
                 — 
                 2.5 
                 1.9 
               
               
                 P48735_C308 
                 — 
                 1.3 
                 1.1 
                 — 
                 — 
               
               
                 Q86UV5_C39 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 P50851_C1704 
                 — 
                 — 
                 1.4 
                 — 
                 2.0 
               
               
                 O94953_C694 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 P19447_C342 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q00535_C157 
                 — 
                 — 
                 1.1 
                 1.7 
                 1.7 
               
               
                 Q9UPT9_C171 
                 2.3 
                 2.1 
                 — 
                 — 
                 9.3 
               
               
                 Q9HB90_C377 
                 — 
                 2.2 
                 — 
                 — 
                 1.5 
               
               
                 P50851_C2675 
                 — 
                 — 
                 — 
                 1.8 
                 1.1 
               
               
                 Q9NYL2_C22 
                 — 
                 — 
                 — 
                 2.1 
                 — 
               
               
                 Q5T1V6_C414 
                 2.0 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q9HB90_C358 
                 — 
                 2.3 
                 — 
                 1.9 
                 1.2 
               
               
                 P16455_C145 
                 — 
                 — 
                 1.0 
                 — 
                 20.0  
               
               
                 Q9Y5T5_C205 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 O00541_C272 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q02556_C306 
                 2.0 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q15910_C503 
                 — 
                 — 
                 — 
                 — 
                 1.7 
               
               
                 Q96RU2_C171 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q16877_C159 
                 — 
                 — 
                 — 
                 — 
                 1.5 
               
               
                 P04150_C302 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q96JH7_C219 
                 — 
                 — 
                 1.0 
                 — 
                 — 
               
               
                 P48200_C137 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 O00622_C39 
                 — 
                 1.2 
                 — 
                 — 
                 — 
               
               
                 Q5T1V6_C453 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 P51617_C608 
                 — 
                 — 
                 — 
                 5.8 
                 2.9 
               
               
                 P42575_C370 
                 4.1 
                 — 
                 — 
                 — 
                 — 
               
               
                 P09086_C346 
                 — 
                 — 
                 0.6 
                 — 
                 — 
               
               
                 Q09472_C1738 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q01201_C109 
                 — 
                 — 
                 — 
                 — 
                 20.0  
               
               
                 Q70CQ2_C741 
                 — 
                 4.2 
                 — 
                 — 
                 — 
               
               
                 P41226_C599 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 P14598_C378 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q9C0C9_C375 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 O00622_C134 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 O00541_C361 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 P43403_C117 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q96FA3_C282 
                 1.5 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q9UPT9_C44 
                 1.7 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q9Y4C1_C251 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q70CQ2_C1090 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 O00622_C70 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 P04150_C622 
                 — 
                 4.8 
                 — 
                 — 
                 — 
               
               
                   
               
               
                   
                 33_500μM —   
                 33_500μM —   
                 34_500μM —   
                 34_500μM —   
                 35_500μM —   
               
               
                 Identifier 
                 invitro_231 
                 invitro_ramos 
                 invitro_231 
                 invitro_ramos 
                 invitro_231 
               
               
                   
               
               
                 Q99873_C109 
                 1.0 
                 0.9 
                 0.8 
                 1.1 
                 0.8 
               
               
                 P24752_C119 
                 0.7 
                 0.7 
                 0.8 
                 — 
                 0.9 
               
               
                 P09211_C48 
                 2.0 
                 0.7 
                 0.8 
                 1.0 
                 0.7 
               
               
                 O14980_C34 
                 0.8 
                 0.9 
                 0.8 
                 1.1 
                 0.8 
               
               
                 P24752_C196 
                 0.9 
                 1.3 
                 0.8 
                 1.0 
                 0.9 
               
               
                 Q15084_C55 
                 3.3 
                 — 
                 0.9 
                 — 
                 0.9 
               
               
                 P24752_C413 
                 1.3 
                 — 
                 0.9 
                 1.3 
                 — 
               
               
                 P63244_C182 
                 — 
                 1.1 
                 — 
                 — 
                 0.9 
               
               
                 P24752_C126 
                 4.3 
                 — 
                 — 
                 1.1 
                 — 
               
               
                 Q15084_C190 
                 3.3 
                 — 
                 0.9 
                 — 
                 0.9 
               
               
                 Q8TAQ2_C145 
                 — 
                 1.5 
                 — 
                 — 
                 0.9 
               
               
                 P68036_C86 
                 — 
                 0.9 
                 — 
                 — 
                 — 
               
               
                 P15374_C95 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q16763_C118 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q16822_C306 
                 — 
                 — 
                 — 
                 — 
                 0.9 
               
               
                 O14980_C528 
                 — 
                 — 
                 — 
                 1.1 
                 — 
               
               
                 O00170_C122 
                 — 
                 — 
                 1.0 
                 — 
                 — 
               
               
                 O75874_C269 
                 1.2 
                 — 
                 — 
                 — 
                 — 
               
               
                 O75362_C286 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 P40763_C259 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q9Y3Z3_C522 
                 0.8 
                 — 
                 — 
                 — 
                 — 
               
               
                 P16455_C150 
                 — 
                 1.9 
                 — 
                 1.4 
                 — 
               
               
                 Q96GG9_C115 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 P00813_C75 
                 — 
                 0.8 
                 — 
                 1.1 
                 — 
               
               
                 O14933_C98 
                 — 
                 1.2 
                 0.8 
                 — 
                 — 
               
               
                 Q14790_C360 
                 3.1 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q15306_C194 
                 — 
                 1.1 
                 — 
                 — 
                 — 
               
               
                 Q6L8Q7_C108 
                 — 
                 — 
                 — 
                 — 
                 0.8 
               
               
                 P48735_C308 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q861UV5_C39 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 P50851_C1704 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 O94953_C694 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 P19447_C342 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q00535_C157 
                 — 
                 — 
                 0.7 
                 — 
                 — 
               
               
                 Q9UPT9_C171 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q9HB90_C377 
                 1.1 
                 — 
                 — 
                 — 
                 — 
               
               
                 P50851_C2675 
                 — 
                 — 
                 — 
                 1.1 
                 — 
               
               
                 Q9NYL2_C22 
                 3.7 
                 — 
                 0.8 
                 — 
                 — 
               
               
                 Q5T1V6_C414 
                 — 
                 — 
                 0.6 
                 — 
                 — 
               
               
                 Q9HB90_C358 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 P16455_C145 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q9Y5T5_C205 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 O00541_C272 
                 1.4 
                 — 
                 — 
                 — 
                 0.8 
               
               
                 Q02556_C306 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q15910_C503 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q96RU2_C171 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q16877_C159 
                 — 
                 — 
                 — 
                 1.4 
                 — 
               
               
                 P04150_C302 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q96JH7_C219 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 P48200_C137 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 O00622_C39 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q5T1V6_C453 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 P51617_C608 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 P42575_C370 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 P09086_C346 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q09472_C1738 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q01201_C109 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q70CQ2_C741 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 P41226_C599 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 P14598_C378 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q9C0C9_C375 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 O00622_C134 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 O00541_C361 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 P43403_C117 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q96FA3_C282 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q9UPT9_C44 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q9Y4C1_C251 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q70CQ2_C1090 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 O00622_C70 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 P04150_C622 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
               
             
               
                 TABLE 1G 
               
               
                   
               
             
            
               
                   
                 35_500μM —   
                 36_500μM —   
                 37_500μM —   
                 38_500μM —   
                 38_500μM —   
               
               
                 Identifier 
                 invitro_ramos 
                 invitro_231 
                 invitro_ramos 
                 invitro_231 
                 invitro_ramos 
               
               
                   
               
               
                 Q99873_C109 
                 1.0 
                 1.0 
                 1.0 
                 0.9 
                 1.4 
               
               
                 P24752_C119 
                 1.0 
                 1.2 
                 0.8 
                 1.0 
                 1.7 
               
               
                 P09211_C48 
                 1.3 
                 1.6 
                 1.2 
                 1.9 
                 — 
               
               
                 O14980_C34 
                 1.3 
                 1.3 
                 0.9 
                 1.0 
                 1.0 
               
               
                 P24752_C196 
                 1.4 
                 1.5 
                 1.0 
                 1.0 
                 1.3 
               
               
                 Q15084_C55 
                 — 
                 — 
                 1.0 
                 1.0 
                 1.3 
               
               
                 P24752_C413 
                 1.3 
                 2.7 
                 0.9 
                 1.1 
                 20.0  
               
               
                 P63244_C182 
                 0.9 
                 1.3 
                 0.9 
                 1.1 
                 — 
               
               
                 P24752_C126 
                 10.4  
                 — 
                 0.9 
                 1.0 
                 1.4 
               
               
                 Q15084_C190 
                 — 
                 — 
                 1.1 
                 1.1 
                 — 
               
               
                 Q8TAQ2_C145 
                 — 
                 — 
                 — 
                 1.1 
                 1.9 
               
               
                 P68036_C86 
                 — 
                 — 
                 — 
                 — 
                 1.5 
               
               
                 P15374_C95 
                 — 
                 — 
                 — 
                 2.7 
                 12.5  
               
               
                 Q16763_C118 
                 — 
                 — 
                 — 
                 1.0 
                 1.0 
               
               
                 Q16822_C306 
                 1.0 
                 — 
                 1.0 
                 1.0 
                 — 
               
               
                 O14980_C528 
                 0.8 
                 — 
                 0.9 
                 1.0 
                 — 
               
               
                 O00170_C122 
                 — 
                 — 
                 — 
                 1.5 
                 1.5 
               
               
                 O75874_C269 
                 — 
                 1.7 
                 — 
                 0.7 
                 — 
               
               
                 O75362_C286 
                 — 
                 — 
                 0.9 
                 0.9 
                 1.2 
               
               
                 P40763_C259 
                 1.1 
                 — 
                 0.9 
                 — 
                 1.5 
               
               
                 Q9Y3Z3_C522 
                 — 
                 — 
                 0.7 
                 — 
                 — 
               
               
                 P16455_C150 
                 1.3 
                 — 
                 1.0 
                 — 
                 1.8 
               
               
                 Q96GG9_C115 
                 0.9 
                 — 
                 0.8 
                 1.2 
                 1.0 
               
               
                 P00813_C75 
                 1.1 
                 — 
                 0.9 
                 — 
                 2.3 
               
               
                 O14933_C98 
                 — 
                 — 
                 — 
                 1.6 
                 1.7 
               
               
                 Q14790_C360 
                 1.3 
                 — 
                 1.0 
                 1.0 
                 4.1 
               
               
                 Q15306_C194 
                 1.0 
                 — 
                 0.9 
                 — 
                 2.1 
               
               
                 Q6L8Q7_C108 
                 — 
                 — 
                 — 
                 0.9 
                 6.8 
               
               
                 P48735_C308 
                 — 
                 1.3 
                 — 
                 1.2 
                 — 
               
               
                 Q86UV5_C39 
                 1.0 
                 — 
                 0.7 
                 3.7 
                 — 
               
               
                 P50851_C1704 
                 1.1 
                 — 
                 1.0 
                 — 
                 2.5 
               
               
                 O94953_C694 
                 1.1 
                 — 
                 1.1 
                 — 
                 2.4 
               
               
                 P19447_C342 
                 — 
                 — 
                 — 
                 1.3 
                 — 
               
               
                 Q00535_C157 
                 — 
                 — 
                 — 
                 0.9 
                 — 
               
               
                 Q9UPT9_C171 
                 1.5 
                 — 
                 — 
                 1.4 
                 — 
               
               
                 Q9HB90_C377 
                 — 
                 — 
                 — 
                 1.0 
                 — 
               
               
                 P50851_C2675 
                 1.0 
                 — 
                 1.0 
                 — 
                 — 
               
               
                 Q9NYL2_C22 
                 — 
                 — 
                 — 
                 1.2 
                 — 
               
               
                 Q5T1V6_C414 
                 1.3 
                 — 
                 1.0 
                 0.9 
                 1.8 
               
               
                 Q9HB90_C358 
                 — 
                 — 
                 — 
                 1.1 
                 — 
               
               
                 P16455_C145 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q9Y5T5_C205 
                 — 
                 — 
                 — 
                 — 
                 1.9 
               
               
                 O00541_C272 
                 1.2 
                 — 
                 1.0 
                 1.0 
                 — 
               
               
                 Q02556_C306 
                 1.2 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q15910_C503 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q96RU2_C171 
                 — 
                 — 
                 — 
                 3.3 
                 — 
               
               
                 Q16877_C159 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 P04150_C302 
                 0.9 
                 — 
                 0.9 
                 — 
                 — 
               
               
                 Q96JH7_C219 
                 — 
                 — 
                 — 
                 — 
                 1.8 
               
               
                 P48200_C137 
                 1.1 
                 — 
                 0.9 
                 — 
                 — 
               
               
                 O00622_C39 
                 — 
                 — 
                 — 
                 0.8 
                 — 
               
               
                 Q5T1V6_C453 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 P51617_C608 
                 — 
                 — 
                 — 
                 — 
                 2.4 
               
               
                 P42575_C370 
                 — 
                 — 
                 0.7 
                 — 
                 — 
               
               
                 P09086_C346 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q09472_C1738 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q01201_C109 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q70CQ2_C741 
                 — 
                 — 
                 1.1 
                 — 
                 4.1 
               
               
                 P41226_C599 
                 1.2 
                 — 
                 — 
                 — 
                 — 
               
               
                 P14598_C378 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q9C0C9_C375 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 O00622_C134 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 O00541_C361 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 P43403_C117 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q96FA3_C282 
                 — 
                 — 
                 — 
                 — 
                 7.0 
               
               
                 Q9UPT9_C44 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q9Y4C1_C251 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q70CQ2_C1090 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 O00622_C70 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 P04150_C622 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                   
               
               
                   
                 39_500μM —   
                 40_500μM —   
                 40_500μM —   
                 41_500μM —   
                 41_500μM —   
               
               
                 Identifier 
                 invitro_231 
                 invitro_231 
                 invitro_ramos 
                 invitro_231 
                 invitro_ramos 
               
               
                   
               
               
                 Q99873_C109 
                 1.5 
                 0.8 
                 1.3 
                 0.9 
                 0.9 
               
               
                 P24752_C119 
                 1.7 
                 0.8 
                 0.9 
                 1.0 
                 0.8 
               
               
                 P09211_C48 
                 2.0 
                 1.6 
                 1.6 
                 1.3 
                 0.9 
               
               
                 O14980_C34 
                 1.3 
                 0.8 
                 1.1 
                 3.1 
                 2.0 
               
               
                 P24752_C196 
                 3.0 
                 0.8 
                 — 
                 1.3 
                 1.0 
               
               
                 Q15084_C55 
                 3.9 
                 0.8 
                 — 
                 0.9 
                 0.8 
               
               
                 P24752_C413 
                 2.7 
                 0.9 
                 — 
                 0.8 
                 0.9 
               
               
                 P63244_C182 
                 1.0 
                 1.0 
                 0.6 
                 — 
                 4.7 
               
               
                 P24752_C126 
                 — 
                 0.9 
                 — 
                 1.0 
                 0.9 
               
               
                 Q15084_C190 
                 7.0 
                 0.9 
                 1.7 
                 1.0 
                 — 
               
               
                 Q8TAQ2_C145 
                 1.2 
                 0.9 
                 1.1 
                 1.8 
                 2.8 
               
               
                 P68036_C86 
                 1.9 
                 0.8 
                 0.9 
                 9.8 
                 7.9 
               
               
                 P15374_C95 
                 — 
                 — 
                 0.9 
                 1.0 
                 0.8 
               
               
                 Q16763_C118 
                 1.4 
                 0.9 
                 0.8 
                 — 
                 3.4 
               
               
                 Q16822_C306 
                 — 
                 — 
                 — 
                 1.2 
                 1.0 
               
               
                 O14980_C528 
                 — 
                 — 
                 — 
                 0.6 
                 — 
               
               
                 O00170_C122 
                 — 
                 — 
                 — 
                 1.1 
                 1.0 
               
               
                 O75874_C269 
                 — 
                 — 
                 0.8 
                 0.8 
                 — 
               
               
                 O75362_C286 
                 20.0  
                 — 
                 — 
                 — 
                 0.6 
               
               
                 P40763_C259 
                 — 
                 — 
                 1.4 
                 0.9 
                 — 
               
               
                 Q9Y3Z3_C522 
                 1.1 
                 0.8 
                 — 
                 0.9 
                 — 
               
               
                 P16455_C150 
                 — 
                 — 
                 1.9 
                 — 
                 0.9 
               
               
                 Q96GG9_C115 
                 — 
                 — 
                 0.9 
                 — 
                 — 
               
               
                 P00813_C75 
                 — 
                 — 
                 0.9 
                 — 
                 1.1 
               
               
                 O14933_C98 
                 — 
                 — 
                 1.3 
                 1.2 
                 1.1 
               
               
                 Q14790_C360 
                 — 
                 — 
                 — 
                 1.0 
                 0.8 
               
               
                 Q15306_C194 
                 — 
                 — 
                 1.1 
                 — 
                 1.2 
               
               
                 Q6L8Q7_C108 
                 3.2 
                 0.8 
                 — 
                 1.3 
                 — 
               
               
                 P48735_C308 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q86UV5_C39 
                 — 
                 — 
                 1.6 
                 — 
                 — 
               
               
                 P50851_C1704 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 O94953_C694 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 P19447_C342 
                 — 
                 — 
                 — 
                 1.1 
                 — 
               
               
                 Q00535_C157 
                 — 
                 — 
                 — 
                 1.5 
                 — 
               
               
                 Q9UPT9_C171 
                 — 
                 — 
                 — 
                 3.0 
                 1.4 
               
               
                 Q9HB90_C377 
                 — 
                 — 
                 — 
                 1.1 
                 — 
               
               
                 P50851_C2675 
                 — 
                 — 
                 — 
                 1.9 
                 — 
               
               
                 Q9NYL2_C22 
                 — 
                 — 
                 — 
                 1.5 
                 — 
               
               
                 Q5T1V6_C414 
                 — 
                 — 
                 1.4 
                 1.2 
                 1.0 
               
               
                 Q9HB90_C358 
                 — 
                 — 
                 — 
                 1.3 
                 — 
               
               
                 P16455_C145 
                 — 
                 — 
                 1.0 
                 1.9 
                 — 
               
               
                 Q9Y5T5_C205 
                 — 
                 — 
                 0.9 
                 0.8 
                 — 
               
               
                 O00541_C272 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q02556_C306 
                 — 
                 — 
                 0.9 
                 — 
                 1.4 
               
               
                 Q15910_C503 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q96RU2_C171 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q16877_C159 
                 — 
                 — 
                 1.2 
                 — 
                 — 
               
               
                 P04150_C302 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q96JH7_C219 
                 — 
                 — 
                 1.9 
                 — 
                 — 
               
               
                 P48200_C137 
                 — 
                 — 
                 1.1 
                 1.2 
                 — 
               
               
                 O00622_C39 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q5T1V6_C453 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 P51617_C608 
                 — 
                 — 
                 — 
                 1.1 
                 — 
               
               
                 P42575_C370 
                 — 
                 — 
                 2.7 
                 — 
                 1.4 
               
               
                 P09086_C346 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q09472_C1738 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q01201_C109 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q70CQ2_C741 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 P41226_C599 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 P14598_C378 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q9C0C9_C375 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 O00622_C134 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 O00541_C361 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 P43403_C117 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q96FA3_C282 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q9UPT9_C44 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q9Y4C1_C251 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q70CQ2_C1090 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 O00622_C70 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 P04150_C622 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
               
             
               
                 TABLE 1H 
               
               
                   
               
             
            
               
                   
                 42_500μM —   
                 43_500μM —   
                 43_500μM —   
                 44_500μM —   
                 45_500μM —   
               
               
                 Identifier 
                 invitro_ramos 
                 invitro_231 
                 invitro_ramos 
                 invitro_231 
                 invitro_231 
               
               
                   
               
               
                 Q99873_C109 
                 0.9 
                 1.4 
                 1.2 
                 0.8 
                 2.2 
               
               
                 P24752_C119 
                 0.8 
                 1.8 
                 1.1 
                 0.8 
                 12.4  
               
               
                 P09211_C48 
                 0.7 
                 4.1 
                 2.2 
                 0.9 
                 19.7  
               
               
                 O14980_C34 
                 0.9 
                 1.1 
                 — 
                 0.8 
                 1.8 
               
               
                 P24752_C196 
                 0.8 
                 2.4 
                 2.3 
                 0.8 
                 20.0  
               
               
                 Q15084_C55 
                 0.9 
                 20.0  
                 20.0  
                 1.0 
                 — 
               
               
                 P24752_C413 
                 0.7 
                 15.9  
                 — 
                 0.8 
                 20.0  
               
               
                 P63244_C182 
                 0.8 
                 0.9 
                 0.9 
                 — 
                 0.9 
               
               
                 P24752_C126 
                 0.8 
                 — 
                 20.0  
                 0.8 
                 20.0  
               
               
                 Q15084_C190 
                 — 
                 20.0  
                 — 
                 1.0 
                 — 
               
               
                 Q8TAQ2_C145 
                 1.0 
                 20.0  
                 — 
                 1.0 
                 — 
               
               
                 P68036_C86 
                 0.8 
                 1.1 
                 1.7 
                 — 
                 — 
               
               
                 P15374_C95 
                 0.9 
                 — 
                 20.0  
                 0.8 
                 — 
               
               
                 Q16763_C118 
                 0.8 
                 — 
                 1.0 
                 0.8 
                 — 
               
               
                 Q16822_C306 
                 0.8 
                 3.3 
                 — 
                 — 
                 3.3 
               
               
                 O14980_C528 
                 — 
                 4.6 
                 — 
                 — 
                 — 
               
               
                 O00170_C122 
                 0.8 
                 — 
                 2.1 
                 — 
                 — 
               
               
                 O75874_C269 
                 — 
                 0.8 
                 — 
                 0.8 
                 20.0  
               
               
                 O75362_C286 
                 1.0 
                 1.9 
                 1.2 
                 — 
                 20.0  
               
               
                 P40763_C259 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q9Y3Z3_C522 
                 — 
                 2.2 
                 — 
                 0.8 
                 — 
               
               
                 P16455_C150 
                 0.8 
                 — 
                 20.0  
                 — 
                 — 
               
               
                 Q96GG9_C115 
                 0.9 
                 — 
                 — 
                 — 
                 — 
               
               
                 P00813_C75 
                 0.8 
                 — 
                 1.2 
                 — 
                 — 
               
               
                 O14933_C98 
                 1.0 
                 — 
                 — 
                 2.0 
                 — 
               
               
                 Q14790_C360 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q15306_C194 
                 1.2 
                 — 
                 3.0 
                 — 
                 — 
               
               
                 Q6L8Q7_C108 
                 — 
                 — 
                 — 
                 0.8 
                 — 
               
               
                 P48735_C308 
                 — 
                 0.8 
                 — 
                 — 
                 1.0 
               
               
                 Q86UV5_C39 
                 — 
                 1.5 
                 — 
                 — 
                 — 
               
               
                 P50851_C1704 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 O94953_C694 
                 0.9 
                 20.0  
                 — 
                 — 
                 — 
               
               
                 P19447_C342 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q00535_C157 
                 — 
                 — 
                 1.2 
                 — 
                 — 
               
               
                 Q9UPT9_C171 
                 1.0 
                 — 
                 4.5 
                 — 
                 — 
               
               
                 Q9HB90_C377 
                 — 
                 — 
                 — 
                 0.7 
                 — 
               
               
                 P50851_C2675 
                 — 
                 1   
                 — 
                 — 
                 — 
               
               
                 Q9NYL2_C22 
                 — 
                 2.9 
                 — 
                 0.8 
                 20.0  
               
               
                 Q5T1V6_C414 
                 — 
                 — 
                 — 
                 0.8 
                 — 
               
               
                 Q9HB90_C358 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 P16455_C145 
                 0.9 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q9Y5T5_C205 
                 1.5 
                 — 
                 — 
                 — 
                 — 
               
               
                 O00541_C272 
                 0.9 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q02556_C306 
                 0.9 
                 — 
                 2.7 
                 — 
                 — 
               
               
                 Q15910_C503 
                 — 
                 20.0  
                 — 
                 — 
                 — 
               
               
                 Q96RU2_C171 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q16877_C159 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 P04150_C302 
                 — 
                 1.5 
                 — 
                 — 
                 — 
               
               
                 Q96JH7_C219 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 P48200_C137 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 O00622_C39 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q5T1V6_C453 
                 1.0 
                 20.0  
                 — 
                 — 
                 — 
               
               
                 P51617_C608 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 P42575_C370 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 P09086_C346 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q09472_C1738 
                 — 
                 2.2 
                 — 
                 — 
                 — 
               
               
                 Q01201_C109 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q70CQ2_C741 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 P41226_C599 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 P14598_C378 
                 — 
                 — 
                 1.2 
                 — 
                 — 
               
               
                 Q9C0C9_C375 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 O00622_C134 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 O00541_C361 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 P43403_C117 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q96FA3_C282 
                 1.2 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q9UPT9_C44 
                 — 
                 — 
                 2.1 
                 — 
                 — 
               
               
                 Q9Y4C1_C251 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q70CQ2_C1090 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 O00622_C70 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 P04150_C622 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                   
               
               
                   
                 46_500μM —   
                 47_500μM —   
                 48_500μM —   
                 49_500μM —   
                 50_500μM —   
               
               
                 Identifier 
                 invitro_231 
                 invitro_231 
                 invitro_231 
                 invitro_231 
                 invitro_231 
               
               
                   
               
               
                 Q99873_C109 
                 0.8 
                 0.9 
                 1.0 
                 2.0 
                 1.0 
               
               
                 P24752_C119 
                 0.8 
                 1.0 
                 1.3 
                 4.9 
                 2.1 
               
               
                 P09211_C48 
                 1.0 
                 2.5 
                 1.1 
                 — 
                 2.3 
               
               
                 O14980_C34 
                 1.0 
                 1.0 
                 1.1 
                 1.9 
                 1.2 
               
               
                 P24752_C196 
                 0.9 
                 1.1 
                 1.3 
                 4.7 
                 3.9 
               
               
                 Q15084_C55 
                 0.8 
                 0.9 
                 1.0 
                 12.8  
                 1.3 
               
               
                 P24752_C413 
                 1.1 
                 0.9 
                 1.1 
                 2.6 
                 9.2 
               
               
                 P63244_C182 
                 0.8 
                 1.1 
                 1.1 
                 — 
                 0.8 
               
               
                 P24752_C126 
                 0.9 
                 1.0 
                 — 
                 20.0  
                 20.0  
               
               
                 Q15084_C190 
                 0.9 
                 1.0 
                 — 
                 7.7 
                 — 
               
               
                 Q8TAQ2_C145 
                 1.0 
                 1.5 
                 1.1 
                 — 
                 2.8 
               
               
                 P68036_C86 
                 1.2 
                 2.0 
                 — 
                 1.9 
                 — 
               
               
                 P15374_C95 
                 1.0 
                 1.0 
                 — 
                 — 
                 1.3 
               
               
                 Q16763_C118 
                 1.0 
                 — 
                 — 
                 — 
                 0.8 
               
               
                 Q16822_C306 
                 0.9 
                 1.0 
                 — 
                 — 
                 2.7 
               
               
                 O14980_C528 
                 0.7 
                 2.2 
                 — 
                 — 
                 — 
               
               
                 O00170_C122 
                 — 
                 — 
                 — 
                 4.8 
                 2.3 
               
               
                 O75874_C269 
                 0.6 
                 0.9 
                 1.0 
                 — 
                 20.0  
               
               
                 O75362_C286 
                 0.9 
                 — 
                 — 
                 1.0 
                 — 
               
               
                 P40763_C259 
                 1.2 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q9Y3Z3_C522 
                 — 
                 — 
                 1.4 
                 3.0 
                 — 
               
               
                 P16455_C150 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q96GG9_C115 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 P00813_C75 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 O14933_C98 
                 — 
                 — 
                 — 
                 — 
                 1.5 
               
               
                 Q14790_C360 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q15306_C194 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q6L8Q7_C108 
                 — 
                 — 
                 — 
                 — 
                 1.8 
               
               
                 P48735_C308 
                 0.2 
                 1.2 
                 1.1 
                 — 
                 2.2 
               
               
                 Q86UV5_C39 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 P50851_C1704 
                 — 
                 — 
                 — 
                 4.0 
                 — 
               
               
                 O94953_C694 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 P19447_C342 
                 1.0 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q00535_C157 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q9UPT9_C171 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q9HB90_C377 
                 — 
                 1.6 
                 1.4 
                 — 
                 — 
               
               
                 P50851_C2675 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q9NYL2_C22 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q5T1V6_C414 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q9HB90_C358 
                 1.1 
                 — 
                 — 
                 — 
                 — 
               
               
                 P16455_C145 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q9Y5T5_C205 
                 1.0 
                 — 
                 — 
                 — 
                 — 
               
               
                 O00541_C272 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q02556_C306 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q15910_C503 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q96RU2_C171 
                 0.9 
                 1.5 
                 — 
                 — 
                 — 
               
               
                 Q16877_C159 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 P04150_C302 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q96JH7_C219 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 P48200_C137 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 O00622_C39 
                 1.9 
                 — 
                 — 
                 — 
                 2.3 
               
               
                 Q5T1V6_C453 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 P51617_C608 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 P42575_C370 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 P09086_C346 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q09472_C1738 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q01201_C109 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q70CQ2_C741 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 P41226_C599 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 P14598_C378 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q9C0C9_C375 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 O00622_C134 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 O00541_C361 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 P43403_C117 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q96FA3_C282 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q9UPT9_C44 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q9Y4C1_C251 
                 1.0 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q70CQ2_C1090 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 O00622_C70 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 P04150_C622 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
               
             
               
                 TABLE 1I 
               
               
                   
               
             
            
               
                   
                 51_500μM —   
                 51_500μM —   
                 52_500μM —   
                 52_500μM —   
                 53_500μM —   
               
               
                 Identifier 
                 invitro_231 
                 invitro_ramos 
                 invitro_231 
                 invitro_ramos 
                 invitro_231 
               
               
                   
               
               
                 Q99873_C109 
                 0.9 
                 9.5 
                 0.9 
                 1.3 
                 0.9 
               
               
                 P24752_C119 
                 0.8 
                 0.9 
                 1.4 
                 0.8 
                 0.9 
               
               
                 P09211_C48 
                 1.1 
                 1.0 
                 1.0 
                 1.9 
                 2.3 
               
               
                 O14980_C34 
                 0.9 
                 1.0 
                 1.0 
                 1.1 
                 0.9 
               
               
                 P24752_C196 
                 1.1 
                 — 
                 1.3 
                 1.5 
                 1.2 
               
               
                 Q15084_C55 
                 2.5 
                 2.7 
                 1.1 
                 1.8 
                 0.9 
               
               
                 P24752_C413 
                 1.0 
                 1.0 
                 1.9 
                 1.5 
                 1.0 
               
               
                 P63244_C182 
                 0.7 
                 0.9 
                 1.0 
                 — 
                 0.9 
               
               
                 P24752_C126 
                 1.0 
                 1.2 
                 1.3 
                 — 
                 — 
               
               
                 Q15084_C190 
                 — 
                 5.6 
                 1.0 
                 1.9 
                 1.0 
               
               
                 Q8TAQ2_C145 
                 — 
                 1.1 
                 0.9 
                 1.8 
                 — 
               
               
                 P68036_C86 
                 — 
                 1.0 
                 0.8 
                 1.3 
                 1.0 
               
               
                 P15374_C95 
                 — 
                 0.9 
                 1.2 
                 — 
                 — 
               
               
                 Q16763_C118 
                 — 
                 0.9 
                 1.2 
                 — 
                 1.0 
               
               
                 Q16822_C306 
                 — 
                 0.8 
                 1.3 
                 1.6 
                 1.3 
               
               
                 O14980_C528 
                 — 
                 0.9 
                 1.3 
                 — 
                 — 
               
               
                 O00170_C122 
                 1.4 
                 — 
                 — 
                 1.4 
                 — 
               
               
                 O75874_C269 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 O75362_C286 
                 0.9 
                 20.0  
                 1.0 
                 — 
                 1.1 
               
               
                 P40763_C259 
                 — 
                 — 
                 2.2 
                 — 
                 — 
               
               
                 Q9Y3Z3_C522 
                 — 
                 — 
                 1.2 
                 — 
                 — 
               
               
                 P16455_C150 
                 — 
                 — 
                 — 
                 2.2 
                 — 
               
               
                 Q96GG9_C115 
                 — 
                 0.8 
                 — 
                 1.0 
                 1.0 
               
               
                 P00813_C75 
                 — 
                 1.0 
                 — 
                 1.2 
                 — 
               
               
                 O14933_C98 
                 — 
                 — 
                 1.4 
                 1.4 
                 — 
               
               
                 Q14790_C360 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q15306_C194 
                 — 
                 1.4 
                 — 
                 1.4 
                 — 
               
               
                 Q6L8Q7_C108 
                 — 
                 — 
                 1.4 
                 6.8 
                 — 
               
               
                 P48735_C308 
                 — 
                 — 
                 1.1 
                 — 
                 0.5 
               
               
                 Q86UV5_C39 
                 — 
                 1.8 
                 0.9 
                 — 
                 — 
               
               
                 P50851_C1704 
                 — 
                 1.1 
                 — 
                 1.1 
                 — 
               
               
                 O94953_C694 
                 — 
                 1.4 
                 — 
                 1.4 
                 — 
               
               
                 P19447_C342 
                 1.4 
                 — 
                 1.0 
                 — 
                 — 
               
               
                 Q00535_C157 
                 — 
                 1.0 
                 — 
                 — 
                 1.2 
               
               
                 Q9UPT9_C171 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q9HB90_C377 
                 0.6 
                 — 
                 — 
                 — 
                 — 
               
               
                 P50851_C2675 
                 — 
                 0.9 
                 — 
                 — 
                 — 
               
               
                 Q9NYL2_C22 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q5T1V6_C414 
                 — 
                 — 
                 — 
                 — 
                 0.8 
               
               
                 Q9HB90_C358 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 P16455_C145 
                 — 
                 20.0  
                 — 
                 — 
                 — 
               
               
                 Q9Y5T5_C205 
                 1.7 
                 3.2 
                 — 
                 — 
                 1.1 
               
               
                 O00541_C272 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q02556_C306 
                 — 
                 1.5 
                 — 
                 — 
                 — 
               
               
                 Q15910_C503 
                 — 
                 — 
                 0.9 
                 — 
                 — 
               
               
                 Q96RU2_C171 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q16877_C159 
                 — 
                 1.1 
                 — 
                 — 
                 — 
               
               
                 P04150_C302 
                 — 
                 — 
                 — 
                 1.8 
                 — 
               
               
                 Q96JH7_C219 
                 — 
                 2.3 
                 — 
                 1.6 
                 — 
               
               
                 P48200_C137 
                 — 
                 — 
                 — 
                 1.3 
                 — 
               
               
                 O00622_C39 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q5T1V6_C453 
                 — 
                 1.8 
                 — 
                 — 
                 — 
               
               
                 P51617_C608 
                 — 
                 1.1 
                 — 
                 17.6  
                 — 
               
               
                 P42575_C370 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 P09086_C346 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q09472_C1738 
                 — 
                 — 
                 1.1 
                 — 
                 — 
               
               
                 Q01201_C109 
                 — 
                 1.6 
                 — 
                 — 
                 — 
               
               
                 Q70CQ2_C741 
                 — 
                 0.9 
                 — 
                 — 
                 — 
               
               
                 P41226_C599 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 P14598_C378 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q9C0C9_C375 
                 — 
                 0.8 
                 — 
                 — 
                 — 
               
               
                 O00622_C134 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 O00541_C361 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 P43403_C117 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q96FA3_C282 
                 — 
                 — 
                 — 
                 20.0  
                 — 
               
               
                 Q9UPT9_C44 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q9Y4C1_C251 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q70CQ2_C1090 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 O00622_C70 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 P04150_C622 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                   
               
               
                   
                 53_500μM —   
                 54_500μM —   
                 55_500μM —   
                 56_500μM —   
                 56_500μM —   
               
               
                 Identifier 
                 invitro_ramos 
                 invitro_231 
                 invitro_2 
                 invitro_231 
                 invitro_ramos 
               
               
                   
               
               
                 Q99873_C109 
                 1.1 
                 1.2 
                 1.0 
                 1.0 
                 1.1 
               
               
                 P24752_C119 
                 0.7 
                 1.0 
                 0.9 
                 1.0 
                 1.2 
               
               
                 P09211_C48 
                 1.2 
                 1.3 
                 1.4 
                 1.9 
                 1.2 
               
               
                 O14980_C34 
                 1.0 
                 1.1 
                 0.9 
                 0.9 
                 0.9 
               
               
                 P24752_C196 
                 0.9 
                 1.1 
                 1.0 
                 1.1 
                 1.0 
               
               
                 Q15084_C55 
                 1.0 
                 1.2 
                 0.9 
                 1.0 
                 1.1 
               
               
                 P24752_C413 
                 — 
                 1.1 
                 1.0 
                 1.0 
                 0.9 
               
               
                 P63244_C182 
                 0.8 
                 — 
                 1.0 
                 1.1 
                 — 
               
               
                 P24752_C126 
                 — 
                 1.1 
                 0.9 
                 0.9 
                 — 
               
               
                 Q15084_C190 
                 1.0 
                 1.2 
                 — 
                 0.9 
                 1.1 
               
               
                 Q8TAQ2_C145 
                 1.2 
                 — 
                 — 
                 1.4 
                 1.2 
               
               
                 P68036_C86 
                 1.0 
                 — 
                 1.0 
                 1.5 
                 1.3 
               
               
                 P15374_C95 
                 0.7 
                 — 
                 — 
                 1.0 
                 1.1 
               
               
                 Q16763_C118 
                 0.8 
                 — 
                 — 
                 1.2 
                 1.1 
               
               
                 Q16822_C306 
                 — 
                 — 
                 — 
                 1.4 
                 — 
               
               
                 O14980_C528 
                 0.8 
                 — 
                 — 
                 20.0  
                 — 
               
               
                 O00170_C122 
                 0.9 
                 — 
                 — 
                 0.8 
                 0.9 
               
               
                 O75874_C269 
                 — 
                 1.1 
                 — 
                 0.9 
                 — 
               
               
                 O75362_C286 
                 — 
                 — 
                 — 
                 1.0 
                 — 
               
               
                 P40763_C259 
                 1.9 
                 1.3 
                 — 
                 — 
                 — 
               
               
                 Q9Y3Z3_C522 
                 0.7 
                 — 
                 — 
                 1.0 
                 1.0 
               
               
                 P16455_C150 
                 1.1 
                 — 
                 — 
                 — 
                 1.4 
               
               
                 Q96GG9_C115 
                 0.9 
                 1.1 
                 — 
                 — 
                 1.0 
               
               
                 P00813_C75 
                 — 
                 — 
                 — 
                 — 
                 0.9 
               
               
                 O14933_C98 
                 1.0 
                 — 
                 — 
                 — 
                 1.1 
               
               
                 Q14790_C360 
                 — 
                 1.2 
                 — 
                 1.0 
                 — 
               
               
                 Q15306_C194 
                 1.0 
                 — 
                 — 
                 — 
                 1.5 
               
               
                 Q6L8Q7_C108 
                 1.1 
                 — 
                 — 
                 — 
                 — 
               
               
                 P48735_C308 
                 — 
                 — 
                 — 
                 1.0 
                 — 
               
               
                 Q86UV5_C39 
                 — 
                 — 
                 — 
                 1.0 
                 — 
               
               
                 P50851_C1704 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 O94953_C694 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 P19447_C342 
                 — 
                 — 
                 — 
                 1.2 
                 — 
               
               
                 Q00535_C157 
                 0.8 
                 — 
                 — 
                 1.1 
                 — 
               
               
                 Q9UPT9_C171 
                 — 
                 — 
                 — 
                 — 
                 1.9 
               
               
                 Q9HB90_C377 
                 1.1 
                 — 
                 — 
                 1.2 
                 — 
               
               
                 P50851_C2675 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q9NYL2_C22 
                 — 
                 1.1 
                 1.2 
                 1.1 
                 — 
               
               
                 Q5T1V6_C414 
                 — 
                 — 
                 — 
                 1.0 
                 1.0 
               
               
                 Q9HB90_C358 
                 0.6 
                 — 
                 — 
                 1.0 
                 1.0 
               
               
                 P16455_C145 
                 1.0 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q9Y5T5_C205 
                 — 
                 — 
                 — 
                 1.1 
                 0.9 
               
               
                 O00541_C272 
                 — 
                 — 
                 1.0 
                 1.1 
                 — 
               
               
                 Q02556_C306 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q15910_C503 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q96RU2_C171 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q16877_C159 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 P04150_C302 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q96JH7_C219 
                 — 
                 — 
                 — 
                 — 
                 1.0 
               
               
                 P48200_C137 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 O00622_C39 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q5T1V6_C453 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 P51617_C608 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 P42575_C370 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 P09086_C346 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q09472_C1738 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q01201_C109 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q70CQ2_C741 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 P41226_C599 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 P14598_C378 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q9C0C9_C375 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 O00622_C134 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 O00541_C361 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 P43403_C117 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q96FA3_C282 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q9UPT9_C44 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q9Y4C1_C251 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q70CQ2_C1090 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 O00622_C70 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 P04150_C622 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                   
               
            
           
         
       
     
     Table 2 illustrates a list of liganded cysteines and their reactivity profiles with the fragment electrophile library from isoTOP-ABPP experiments performed in situ. Table 2 further shows the accession number (or the protein identifier) of the protein. 
     
       
         
           
               
               
               
               
               
               
               
             
               
                 TABLE 2A 
               
               
                   
               
               
                   
                   
                 SEQ ID 
                 2_200μM —   
                 4_100μM —   
                 8_200μM —   
                 9_200μM —   
               
               
                 Identifier 
                 Protein 
                 NO: 
                 insitu_231 
                 insitu_231 
                 insitu_231 
                 insitu_231 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
               
               
               
            
               
                 P04406_C152 
                 GAPDH Glyceraldehyde-3-phosphate 
                 16 
                 20.0  
                 1.6 
                 1.1 
                 1.7 
               
               
                   
                 dehydrogenase 
               
               
                 P61978_C132 
                 HNRNPK Heterogeneous nuclear 
                 768 
                 5.0 
                 3.8 
                 4.2 
                 1.4 
               
               
                   
                 ribonucleoprotein K 
               
               
                 Q13526_C113 
                 PIN1 Peptidyl-prolyl cis-trans isomerase 
                 1.9 
                 20.0  
                 3.4 
                 2.6 
                 3.3 
               
               
                   
                 NIMA-interacting 1 
               
               
                 P24752_C119 
                 ACAT1 Acetyl-CoA acetyltransferase, 
                 22 
                 2.6 
                 3.0 
                 5.5 
                 3.8 
               
               
                   
                 mitochondrial 
               
               
                 P24752_C413 
                 ACAT1 Acetyl-CoA acetyltransferase, 
                 56 
                 20.0  
                 4.5 
                 20.0  
                 19.5  
               
               
                   
                 mitochondrial 
               
               
                 Q9NUY8_C283 
                 TBC1D23 TBC1 domain family member 23 
                 101 
                 4.1 
                 2.1 
                 4.9 
                 2.1 
               
               
                 P13667_C206 
                 PDIA4 Protein disulfide-isomerase A4 
                 36 
                 2.6 
                 6.8 
                 15.2  
                 1.1 
               
               
                 P12268_C140 
                 IMPDH2 Inosine-5-monophosphate 
                 45 
                 1.3 
                 1.0 
                 0.9 
                 1.2 
               
               
                   
                 dehydrogenase 2 
               
               
                 Q15365_C194 
                 PCBP1 Poly(rC)-binding protein 1 
                 29 
                 5.1 
                 1.4 
                 1.4 
                 10.1  
               
               
                 Q9NVC6_C649 
                 MED17 Mediator of RNA polymerase II 
                 211 
                 7.7 
                 1.7 
                 3.2 
                 2.2 
               
               
                   
                 transcription subunit 17 
               
               
                 P42166_C561 
                 TMPO Lamina-associated polypeptide 2, 
                 88 
                 8.3 
                 20.0  
                 4.6 
                 3.7 
               
               
                   
                 isoform alpha 
               
               
                 Q9Y696_C35 
                 CLIC4 Chloride intracellular channel protein 
                 21 
                 1.7 
                 20.0  
                 4.7 
                 2.6 
               
               
                   
                 4 
               
               
                 P10599_C32 
                 TXN Thioredoxin 
                 34 
                 7.9 
                 3.3 
                 5.9 
                 20.0  
               
               
                 P31943_C267 
                 HNRNPH1 Heterogeneous nuclear 
                 769 
                 3.8 
                 6.0 
                 5.3 
                 2.1 
               
               
                   
                 ribonucleoprotein H 
               
               
                 Q86SX6_C67 
                 GLRX5 Glutaredoxin-related protein 5, 
                 26 
                 1.1 
                 1.4 
                 1.0 
                 5.1 
               
               
                   
                 mitochondrial 
               
               
                 P15121_C299 
                 AKR1B1 Aldose reductase 
                 48 
                 0.9 
                 1.0 
                 1.7 
                 1.4 
               
               
                 P52597_C267 
                 HNRNPF Heterogeneous nuclear 
                 108 
                 4.2 
                 20.0  
                 — 
                 3.2 
               
               
                   
                 ribonucleoprotein F 
               
               
                 Q9ULV4_C420 
                 CORO1C Coronin-1C 
                 770 
                 3.0 
                 1.3 
                 4.6 
                 2.0 
               
               
                 P62888_C92 
                 RPL30 60S ribosomal protein L30 
                 100 
                 1.0 
                 2.7 
                 1.5 
                 1.3 
               
               
                 Q9NQR4_C153 
                 NIT2 Omega-amidase NIT2 
                 47 
                 13.1  
                 0.7 
                 20.0  
                 20.0  
               
               
                 P42765_C92 
                 ACAA2 3-ketoacyl-CoA thiolase, 
                 71 
                 20.0  
                 3.7 
                 20.0  
                 4.3 
               
               
                   
                 mitochondrial 
               
               
                 Q15084_C55 
                 PDIA6 Protein disulfide-isomerase A6 
                 51 
                 3.0 
                 4.9 
                 4.4 
                 2.1 
               
               
                 Q96HE7_C241 
                 ERO1L ERO1-like protein alpha 
                 61 
                 2.4 
                 3.0 
                 3.7 
                 — 
               
               
                 Q99439_C164 
                 CNN2 Calponin-2 
                 41 
                 — 
                 1.5 
                 1.1 
                 4.7 
               
               
                 P25205_C119 
                 MCM3 DNA replication licensing factor 
                 74 
                 3.5 
                 4.3 
                 3.5 
                 1.9 
               
               
                   
                 MCM3 
               
               
                 Q9NS86_C187 
                 LANCL2 LanC-like protein 2 
                 203 
                 — 
                 1.6 
                 6.1 
                 2.5 
               
               
                 Q15233_C145 
                 NONO Non-POU domain-containing 
                 72 
                 — 
                 1.6 
                 12.0  
                 1.4 
               
               
                   
                 octamer-binding protein 
               
               
                 Q9BRA2_C43 
                 TXNDC17 Thioredoxin domain-containing 
                 62 
                 15.5  
                 3.5 
                 20.0  
                 20.0  
               
               
                   
                 protein 17 
               
               
                 P35611_C68 
                 ADD1 Alpha-adducin 
                 771 
                 5.8 
                 4.3 
                 2.4 
                 4.3 
               
               
                 O75521_C380 
                 ECI2 Enoyl-CoA delta isomerase 2, 
                 155 
                 0.6 
                 1.6 
                 0.8 
                 0.7 
               
               
                   
                 mitochondrial 
               
               
                 Q9BXW7_C392 
                 CECR5 Cat eye syndrome critical region 
                 772 
                 3.6 
                 2.2 
                 3.2 
                 1.5 
               
               
                   
                 protein 5 
               
               
                 P30101_C406 
                 PDIA3 Protein disulfide-isomerase A3 
                 773 
                 3.2 
                 9.0 
                 20.0  
                 1.4 
               
               
                 Q96AB3_C114 
                 ISOC2 Isochorismatase domain-containing 
                 159 
                 1.6 
                 0.8 
                 4.7 
                 — 
               
               
                   
                 protein 2, mitochondria 
               
               
                 P13667_C555 
                 PDIA4 Protein disulfide-isomerase A4 
                 774 
                 3.2 
                 9.0 
                 20.0  
                 1.4 
               
               
                 Q09161_C44 
                 NCBP1 Nuclear cap-binding protein 
                 102 
                 2.1 
                 1.8 
                 2.0 
                 — 
               
               
                   
                 subunit 1 
               
               
                 P78417_C32 
                 GSTO1 Glutathione S-transferase omega-1 
                 32 
                 — 
                 19.9  
                 20.0  
                 — 
               
               
                 Q9ULW0_C536 
                 TPX2 Targeting protein for Xklp2 
                 437 
                 20.0  
                 20.0  
                 20.0  
                 5.7 
               
               
                 Q9NRG0_C55 
                 CHRAC1 Chromatin accessibility complex 
                 252 
                 20.0  
                 20.0  
                 7.4 
                 2.9 
               
               
                   
                 protein 1 
               
               
                 Q96T76_C848 
                 MMS19 nucleotide excision repair protein 
                 114 
                 3.9 
                 20.0  
                 1.7 
                 20.0  
               
               
                   
                 homolog 
               
               
                 Q8TAQ2_C145 
                 SMARCC2 SWI/SNF complex subunit 
                 775 
                 4.6 
                 3.1 
                 — 
                 — 
               
               
                   
                 SMARCC2 
               
               
                 Q9BVC5_C10 
                 C2orf49 Ashwin 
                 168 
                 2.7 
                 3.3 
                 4.5 
                 — 
               
               
                 Q7Z2W4_C645 
                 ZC3HAV1 Zinc finger CCCH-type antiviral 
                 776 
                 — 
                 4.4 
                 5.1 
                 3.0 
               
               
                   
                 protein 1 
               
               
                 Q9BQ69_C186 
                 MACROD1 O-acetyl-ADP-ribose 
                 777 
                 4.8 
                 1.8 
                 5.0 
                 1.2 
               
               
                   
                 deacetylase MACROD1 
               
               
                 Q16831_C162 
                 UPP1 Uridine phosphorylase 1 
                 364 
                 1.2 
                 1.0 
                 20.0  
                 7.7 
               
               
                 P30101_C57 
                 PDIA3 Protein disulfide-isomerase A3 
                 133 
                 2.2 
                 20.0  
                 20.0  
                 — 
               
               
                 P12268_C331 
                 IMPDH2 Inosine-5-monophosphate 
                 144 
                 12.1  
                 4.6 
                 — 
                 1.3 
               
               
                   
                 dehydrogenase 2 
               
               
                 O95571_C170 
                 ETHE1 Protein ETHE1, mitochondrial 
                 176 
                 3.8 
                 2.3 
                 6.8 
                 2.0 
               
               
                 O00299_C24 
                 CLIC1 Chloride intracellular channel 
                 69 
                 9.5 
                 20.0  
                 10.3  
                 3.0 
               
               
                   
                 protein 1 
               
               
                 O14879_C343 
                 IFIT3 Interferon-induced protein with 
                 308 
                 7.6 
                 6.6 
                 2.1 
                 17.2  
               
               
                   
                 tetratricopeptide 
               
               
                 Q96CM8_C64 
                 ACSF2 Acyl-CoA synthetase family member 
                 194 
                 20.0  
                 20.0  
                 20.0  
                 — 
               
               
                   
                 2, mitochondrial 
               
               
                 P51946_C244 
                 CCNH Cyclin-H 
                 778 
                 1.9 
                 5.3 
                 — 
                 — 
               
               
                 P49588_C773 
                 AARS Alanine--tRNA ligase, cytoplasmic 
                 122 
                 — 
                 1.3 
                 1.5 
                 1.5 
               
               
                 Q96RN5_C618 
                 MED15 Mediator of RNA polymerase II 
                 171 
                 6.4 
                 4.5 
                 20.0  
                 — 
               
               
                   
                 transcription subuni 
               
               
                 O15294_C758 
                 OGT UDP-N-acetylglucosamine--peptide N- 
                 104 
                 2.6 
                 6.4 
                 2.4 
                 2.1 
               
               
                   
                 acetylglucosami 
               
               
                 P46734_C207 
                 MAP2K3 Dual specificity mitogen-activated 
                 184 
                 0.8 
                 0.6 
                 0.8 
                 3.3 
               
               
                   
                 protein kinase 
               
               
                 Q96S55_C272 
                 WRNIP1 ATPase WRNIP1 
                 215 
                 2.2 
                 3.7 
                 1.2 
                 4.5 
               
               
                 O95229_C54 
                 ZWINT ZW10 interactor 
                 779 
                 3.4 
                 12.4  
                 3.1 
                 3.7 
               
               
                 O60610_C1227 
                 DIAPH1 Protein diaphanous homolog 1 
                 780 
                 2.2 
                 1.6 
                 — 
                 1.5 
               
               
                 Q13428_C38 
                 TCOF1 Treacle protein 
                 150 
                 3.3 
                 2.8 
                 2.0 
                 — 
               
               
                 Q9Y277_C65 
                 VDAC3 Voltage-dependent anion-selective 
                 512 
                 3.3 
                 4.7 
                 6.2 
                 — 
               
               
                   
                 channel protein 
               
               
                 P57764_C268 
                 GSDMD Gasdermin-D 
                 110 
                 20.0  
                 20.0  
                 8.4 
                 — 
               
               
                 Q9Y3A3_C134 
                 MOB4 MOB-like protein phocein 
                 121 
                 — 
                 1.2 
                 1.6 
                 20.0  
               
               
                 Q02252_C317 
                 ALDH6A1 Methylmalonate-semialdehyde 
                 265 
                 10.3  
                 14.4  
                 — 
                 — 
               
               
                   
                 dehydrogenase 
               
               
                 Q9NYL9_C132 
                 TMOD3 Tropomodulin-3 
                 130 
                 2.2 
                 0.8 
                 0.9 
                 7.6 
               
               
                 P83731_C6 
                 RPL24 60S ribosomal protein L24 
                 147 
                 2.4 
                 0.7 
                 — 
                 4.3 
               
               
                 O95336_C32 
                 PGLS 6-phosphogluconolactonase 
                 55 
                 14.9  
                 — 
                 20.0  
                 6.7 
               
               
                 Q13155_C291 
                 AIMP2 Aminoacyl tRNA synthase complex- 
                 83 
                 20.0  
                 20.0  
                 2.4 
                 1.9 
               
               
                   
                 interacting multif 
               
               
                 Q13418_C346 
                 ILK Integrin-linked protein kinase 
                 149 
                 1.4 
                 0.8 
                 — 
                 2.7 
               
               
                 A6NDU8_C179 
                 C5orf51 UPF0600 protein C5orf51 
                 298 
                 4.2 
                 3.0 
                 — 
                 20.0  
               
               
                 Q9UKF6_C498 
                 CPSF3 Cleavage and polyadenylation 
                 118 
                 6.2 
                 3.5 
                 20.0  
                 — 
               
               
                   
                 specificity factor su 
               
               
                 Q96F86_C413 
                 EDC3 Enhancer of mRNA-decapping protein 
                 141 
                 20.0  
                 20.0  
                 — 
                 — 
               
               
                   
                 3 
               
               
                 P42224_C492 
                 STAT1 Signal transducer and activator of 
                 228 
                 16.9  
                 — 
                 — 
                 3.1 
               
               
                   
                 transcription 1 
               
               
                 P11216_C326 
                 PYGB Glycogen phosphorylase, brain form 
                 366 
                 — 
                 1.7 
                 20.0  
                 2.6 
               
               
                 P21980_C277 
                 TGM2 Protein-glutamine gamma- 
                 356 
                 0.7 
                 0.5 
                 0.7 
                 2.3 
               
               
                   
                 glutamyltransferase 2 
               
               
                 Q9HAV7_C124 
                 GRPEL1 GrpE protein homolog 1, 
                 206 
                 3.2 
                 1.7 
                 2.2 
                 4.7 
               
               
                   
                 mitochondrial 
               
               
                 P24752_C126 
                 ACAT1 Acetyl-CoA acetyltransferase, 
                 89 
                 9.1 
                 2.8 
                 4.5 
                 14.1  
               
               
                   
                 mitochondrial 
               
               
                 Q9NQ88_C161 
                 TIGAR Fructose-2,6-bisphosphatase TIGAR 
                 117 
                 6.0 
                 — 
                 — 
                 2.6 
               
               
                 Q13155_C23 
                 AIMP2 Aminoacyl tRNA synthase complex- 
                 132 
                 — 
                 2.8 
                 2.7 
               
               
                   
                 interacting multifunctional protein 2 
               
               
                 Q9NQW6_C712 
                 ANLN Actin-binding protein anillin 
                 281 
                 — 
                 4.1 
                 14.1  
                 3.1 
               
               
                 P51649_C340 
                 ALDH5A1 Succinate-semialdehyde 
                 189 
                 1.9 
                 1.0 
                 2.7 
                 — 
               
               
                   
                 dehydrogenase, mitochondria 
               
               
                 Q15021_C439 
                 NCAPD2 Condensin complex subunit 1 
                 139 
                 — 
                 2.2 
                 0.6 
                 6.1 
               
               
                 Q5T0N5_C69 
                 FNBP1L Formin-binding protein 1-like 
                 418 
                 20.0  
                 20.0  
                 3.6 
                 — 
               
               
                 P38606_C138 
                 ATP6V1A V-type proton ATPase catalytic 
                 201 
                 — 
                 20.0  
                 20.0  
                 20.0  
               
               
                   
                 subunit A 
               
               
                 Q9HCC0_C216 
                 MCCC2 Methylcrotonoyl-CoA carboxylase 
                 363 
                 4.6 
                 5.9 
                 3.9 
                 — 
               
               
                   
                 beta chain, mitoch 
               
               
                 Q9NQC3_C1101 
                 RTN4 Reticulon-4 
                 247 
                 12.0  
                 20.0  
                 — 
                 20.0  
               
               
                 P35754_C23 
                 GLRX Glutaredoxin-1 
                 142 
                 — 
                 20.0  
                 — 
                 — 
               
               
                 Q99757_C90 
                 TXN2 Thioredoxin, mitochondrial 
                 208 
                 10.1  
                 3.6 
                 4.5 
                 20.0  
               
               
                 Q9Y3D0_C93 
                 FAM96B Mitotic spindle-associated MMXD 
                 179 
                 20.0  
                 20.0  
                 — 
                 — 
               
               
                   
                 complex subunit MIP18 
               
               
                 Q9UMS0_C213 
                 NFU1 iron-sulfur cluster scaffold homolog, 
                 394 
                 7.4 
                 4.4 
                 — 
                 — 
               
               
                   
                 mitochondrial 
               
               
                 Q9NXV6_C516 
                 CDKN2AIP CDKN2A-interacting protein 
                 255 
                 20.0  
                 — 
                 — 
                 6.6 
               
               
                 Q96RS6_C376 
                 NUDCD1 NudC domain-containing 
                 79 
                 — 
                 1.6 
                 — 
                 2.2 
               
               
                   
                 protein 1 
               
               
                 Q14997_C1840 
                 PSME4 Proteasome activator complex subunit 
                 257 
                 2.8 
                 20.0  
                 20.0  
                 — 
               
               
                   
                 4 
               
               
                 P50570_C27 
                 DNM2 Dynamin-2 
                 73 
                 4.6 
                 2.2 
                 — 
                 — 
               
               
                 Q86YH6_C71 
                 PDSS2 Decapreiryl-diphosphate synthase 
                 401 
                 20.0  
                 20.0  
                 — 
                 — 
               
               
                   
                 subunit 2 
               
               
                 Q99497_C106 
                 PARK7 Protein DJ-1 
                 109 
                 — 
                 0.9 
                 — 
                 — 
               
               
                 Q9UJW0_C258 
                 DCTN4 Dynactin subunit 4 
                 103 
                 4.0 
                 — 
                 20.0  
                 — 
               
               
                 Q9BUH6_C180 
                 C9orf142 Uncharacterized protein C9orf142 
                 348 
                 — 
                 1.2 
                 6.6 
                 2.8 
               
               
                 P24752_C196 
                 ACAT1 Acetyl-CoA acetyltransferase, 
                 33 
                 20.0  
                 3.5 
                 — 
                 5.8 
               
               
                   
                 mitochondrial 
               
               
                 Q13162_C51 
                 PRDX4 Peroxiredoxin-4 
                 781 
                 4.6 
                 1.2 
                 1.4 
                 3.3 
               
               
                 Q9BTA9_C553 
                 WAC WW domain-containing adapter protein 
                 153 
                 17.6  
                 17.8  
                 9.6 
                 — 
               
               
                   
                 with coiled-coil 
               
               
                 P48643_C253 
                 CCT5 T-complex protein 1 subunit epsilon 
                 126 
                 — 
                 0.8 
                 0.8 
                 — 
               
               
                 O75362_C286 
                 ZNF217 Zinc finger protein 217 
                 268 
                 8.9 
                 — 
                 — 
                 — 
               
               
                 O60825_C158 
                 PFKFB2 6-phosphofructo-2-kinase/fructose- 
                 272 
                 0.7 
                 — 
                 — 
                 — 
               
               
                   
                 2,6-bisphosphata 
               
               
                 Q8NBS9_C350 
                 TXNDC5 Thioredoxin domain-containing 
                 136 
                 — 
                 2.4 
                 — 
                 1.7 
               
               
                   
                 protein 5 
               
               
                 Q9NYL2_C22 
                 MLTK Mitogen-activated protein kinase 
                 430 
                 5.5 
                 20.0  
                 1.4 
                 10.3  
               
               
                   
                 MLTK 
               
               
                 P27707_C9 
                 DCK Deoxy cytidine kinase 
                 93 
                 — 
                 1.4 
                 — 
                 4.9 
               
               
                 Q93009_C223 
                 USP7 Ubiquitin carboxyl-terminal hydrolase 
                 782 
                 — 
                 6.8 
                 20.0  
                 — 
               
               
                   
                 7 
               
               
                 O14929_C101 
                 HAT1 Histone acetyltransferase type B 
                 154 
                 — 
                 — 
                 — 
                 9.0 
               
               
                   
                 catalytic subunit 
               
               
                 Q9UPQ0_C140 
                 LIMCH1 LIM and calponin homology 
                 783 
                 20.0  
                 — 
                 20.0  
                 — 
               
               
                   
                 domains-containing protein 
               
               
                 Q96NY7_C487 
                 CLIC6 Chloride intracellular channel 
                 447 
                 — 
                 20.0  
                 5.1 
                 3.6 
               
               
                   
                 protein 6 
               
               
                 Q9NQ88_C114 
                 TIGAR Fructose-2,6-bisphosphatase TIGAR 
                 143 
                 2.8 
                 — 
                 — 
                 1.9 
               
               
                 Q14790_C360 
                 CASP8 Caspase-8 
                 335 
                 20.0  
                 20.0  
                 — 
                 — 
               
               
                 P04183_C230 
                 TK1 Thymidine kinase, cytosolic 
                 784 
                 1.9 
                 0.8 
                 — 
                 10.0  
               
               
                 P68366_C54 
                 TUBA4A Tubulin alpha-4A chain 
                 137 
                 9.7 
                 0.8 
                 0.9 
                 — 
               
               
                 Q13428_C1298 
                 TCOF1 Treacle protein 
                 785 
                 4.7 
                 5.6 
                 20.0  
                 — 
               
               
                 Q5MNZ6_C63 
                 WDR45L WD repeat domain 
                 434 
                 — 
                 2.0 
                 20.0  
                 — 
               
               
                   
                 phosphoinositide-interacting protein 
               
               
                 O14980_C528 
                 XPO1 Exportin-1 
                 786 
                 20.0  
                 1.9 
                 — 
                 — 
               
               
                 Q86W42_C35 
                 THOC6 THO complex subunit 6 homolog 
                 217 
                 — 
                 — 
                 — 
                 20.0  
               
               
                 Q9Y6G9_C51 
                 DYNC1LI1 Cytoplasmic dynein 1 light 
                 107 
                 — 
                 3.5 
                 4.1 
                 — 
               
               
                   
                 intermediate chain 1 
               
               
                 Q9NY27_C22 
                 PPP4R2 Serine/threonine-protein phosphatase 
                 282 
                 20.0  
                 20.0  
                 — 
               
               
                   
                 4 regulatory 
               
               
                 Q8NFH5_C255 
                 NUP35 Nucleoporin NUP53 
                 386 
                 5.1 
                 3.9 
                 — 
                 — 
               
               
                 Q9Y676_C128 
                 MRPS18B 28S ribosomal protein S18b, 
                 495 
                 10.2  
                 2.3 
                 1.0 
                 — 
               
               
                   
                 mitochondrial 
               
               
                 P35658_C728 
                 NUP214 Nuclear pore complex protein 
                 311 
                 3.9 
                 1.7 
                 — 
                 — 
               
               
                   
                 Nup214 
               
               
                 Q9NTX5_C133 
                 ECHDC1 Ethylmalonyl-CoA decarboxylase 
                 532 
                 1.5 
                 1.7 
                 2.0 
                 — 
               
               
                 Q15118_C71 
                 PDK1 
                 623 
                 20.0  
                 20.0  
                 20.0  
                 — 
               
               
                 Q00765_C18 
                 REEP5 Receptor expression-enhancing 
                 344 
                 — 
                 20.0  
                 2.7 
                 — 
               
               
                   
                 protein 5 
               
               
                 P22307_C71 
                 SCP2 Non-specific lipid-transfer protein 
                 787 
                 3.2 
                 2.7 
                 20.0  
                 — 
               
               
                 O75521_C312 
                 ECI2 Enoyl-CoA delta isomerase 2, 
                 788 
                 0.7 
                 1.0 
                 0.5 
                 0.5 
               
               
                   
                 mitochondrial 
               
               
                 P49189_C288 
                 ALDH9A1 4-trimethylaminobutyraldehyde 
                 236 
                 — 
                 — 
                 — 
                 20.0  
               
               
                   
                 dehydrogenase 
               
               
                 Q5T440_C170 
                 IBA57 Putative transferase CAF17, 
                 608 
                 14.0  
                 1.5 
                 — 
                 — 
               
               
                   
                 mitochondrial 
               
               
                 Q15084_C190 
                 PDIA6 Protein disulfide-isomerase A6 
                 96 
                 — 
                 20.0  
                 5.2 
                 — 
               
               
                 Q96C19_C172 
                 EFHD2 EF-hand domain-containing protein 
                 246 
                 — 
                 5.3 
                 — 
                 2.8 
               
               
                   
                 D2 
               
               
                 P22061_C102 
                 PCMT1 Protein-L-isoaspartate(D-aspartate) 
                 163 
                 — 
                 2.8 
                 4.5 
                 1.2 
               
               
                   
                 O-methyltransferase 
               
               
                 Q9NP73_C86 
                 ALG13 UDP-N-acetylglucosamine 
                 528 
                 20.0  
                 20.0  
                 — 
                 — 
               
               
                   
                 transferase subunit ALG13 
               
               
                 Q9BRF8_C54 
                 CPPED1 Calcineurin-like phosphoesterase 
                 239 
                 — 
                 20.0  
                 — 
                 2.4 
               
               
                   
                 domain-containing 
               
               
                 Q6ICB0_C108 
                 DESI1 Desumoylating isopeptidase 1 
                 197 
                 20.0  
                 — 
                 20.0  
                 — 
               
               
                 P29590_C389 
                 PML Protein PML 
                 304 
                 15.6  
                 — 
                 — 
                 — 
               
               
                 P07858_C211 
                 CTSB Cathepsin B 
                 323 
                 — 
                 2.3 
                 — 
                 5.0 
               
               
                 Q9NX18_C83 
                 SDHAF2 Succinate dehydrogenase assembly 
                 658 
                 3.1 
                 3.0 
                 — 
                 — 
               
               
                   
                 factor 2, mitochondrial 
               
               
                 P46109_C249 
                 CRKL Crk-like protein VPCAYDK 
                 99 
                 20.0  
                 — 
                 — 
                 6.7 
               
               
                   
                 K.RVPC*AYDK.T 
               
               
                 P45984_C177 
                 MAPK9 Mitogen-activated protein kinase 9 
                 302 
                 — 
                 12.0  
                 20.0  
                 — 
               
               
                 P19447_C342 
                 ERCC3 TFIIH basal transcription factor 
                 402 
                 — 
                 — 
                 12.4  
                 — 
               
               
                   
                 complex helicase 
               
               
                 P42166_C341 
                 TMPO Lamina-associated polypeptide 2, 
                 175 
                 10.4  
                 — 
                 4.4 
                 — 
               
               
                   
                 isoform alpha 
               
               
                 Q8N1F7_C522 
                 NUP93 Nuclear pore complex protein Nup93 
                 275 
                 — 
                 — 
                 20.0  
                 — 
               
               
                 Q86UY8_C276 
                 NT5DC3 5-nucleotidase domain-containing 
                 789 
                 3.8 
                 — 
                 — 
                 — 
               
               
                   
                 protein 3 
               
               
                 Q8WWI1_C228 
                 LMO7 LIM domain only protein 7 
                 504 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q9NWA0_C139 
                 MED9 Mediator of RNA polymerase II 
                 654 
                 4.3 
                 3.4 
                 — 
                 — 
               
               
                   
                 transcription subunit 
               
               
                 P09110_C381 
                 ACAA1 3-ketoacyl-CoA thiolase, 
                 205 
                 — 
                 — 
                 0.8 
                 — 
               
               
                   
                 peroxisomal 
               
               
                 Q2NL82_C126 
                 TSR1 Pre-rRNA-processing protein TSR1 
                 233 
                 20.0  
                 13.8  
                 — 
                 — 
               
               
                   
                 homolog 
               
               
                 Q5JPI3_C308 
                 C3orf38 Uncharacterized protein C3orf38 
                 544 
                 2.9 
                 — 
                 — 
                 — 
               
               
                 P23919_C163 
                 DTYMK Thymidylate kinase 
                 173 
                 — 
                 0.4 
                 0.6 
                 — 
               
               
                 Q96EB1_C218 
                 ELP4 Elongator complex protein 4 
                 466 
                 — 
                 20.0  
                 — 
                 8.4 
               
               
                 Q96FX7_C209 
                 TRMT61A tRNA (adenine(58)-N(1))- 
                 313 
                 20.0  
                 2.4 
                 — 
                 — 
               
               
                   
                 methyltransferase catalytic 
               
               
                 O14933_C98 
                 UBE2L6 Ubiquitin/ISG15-conjugating 
                 331 
                 — 
                 3.0 
                 — 
                 — 
               
               
                   
                 enzyme E2 L6 
               
               
                 Q29RF7_C242 
                 PDS5A Sister chromatid cohesion protein 
                 232 
                 — 
                 3.0 
                 1.0 
                 — 
               
               
                   
                 PDS5 homolog A 
               
               
                 Q96T76_C819 
                 MMS19 MMS19 nucleotide excision repair 
                 181 
                 — 
                 — 
                 — 
                 — 
               
               
                   
                 protein homolog 
               
               
                 P23919_C117 
                 DTYMK Thymidylate kinase 
                 267 
                 — 
                   
                 0.4 
                 7.3 
               
               
                 Q15149_C4574 
                 PLEC Plectin 
                 336 
                 — 
                 4.2 
                 — 
                 0.8 
               
               
                 Q96RP9_C153 
                 GFM1 Elongation factor G, mitochondrial 
                 524 
                 — 
                 1.0 
                 — 
                 — 
               
               
                 P04818_C199 
                 TYMS Thymidylate synthase 
                 406 
                 20.0  
                 20.0  
                 — 
                 — 
               
               
                 P27708_C73 
                 CAD CAD protein 
                 191 
                 3.1 
                 — 
                 20.0  
                 — 
               
               
                 P55265_C1224 
                 ADAR Double-stranded RNA-specific 
                 359 
                 9.1 
                 — 
                 — 
                 — 
               
               
                   
                 adenosine deaminase 
               
               
                 Q9Y3D2_C105 
                 MSRB2 Methionine-R-sulfoxide reductase 
                 403 
                   
                 20.0  
                 20.0  
                 — 
               
               
                   
                 B2, mitochondrial 
               
               
                 O00244_C12 
                 ATOX1 Copper transport protein ATOX1 
                 365 
                 — 
                 — 
                 — 
                 4.7 
               
               
                 Q8WV74_C207 
                 NUDT8 Nucleoside diphosphate-linked 
                 468 
                 20.0  
                 20.0  
                 20.0  
                 — 
               
               
                   
                 moiety X motif 8, mitochondrial 
               
               
                 Q9NRW3_C130 
                 APOBEC3C Probable DNA dC- dU-editing 
                 358 
                 20.0  
                 20.0  
                 — 
                 — 
               
               
                   
                 enzyme APOBEC-3C 
               
               
                 P24468_C326 
                 NR2F2 COUP transcription factor 2 
                 790 
                 20.0  
                 20.0  
                 20.0  
                 — 
               
               
                 P42166_C684 
                 TMPO Lamina-associated polypeptide 2, 
                 312 
                 — 
                 — 
                 4.6 
                 — 
               
               
                   
                 isoform alpha 
               
               
                 Q96EY5_C231 
                 FAM125A Multivesicular body subunit 12A 
                 540 
                 4.1 
                 1.7 
                 — 
                 1.9 
               
               
                 P14635_C238 
                 CCNB1 G2/mitotic-specific cyclin-B1 
                 448 
                 — 
                 — 
                 — 
                 3.7 
               
               
                 Q8NDH3_C81 
                 NPEPL1 Probable aminopeptidase NPEPL1 
                 791 
                 20.0  
                 20.0  
                 20.0  
                 — 
               
               
                 Q9P0J1_C149 
                 PDP1 
                 276 
                 20.0  
                 — 
                 — 
                 — 
               
               
                 Q96P48_C900 
                 ARAP1 Arf-GAP with Rho-GAP domain, 
                 433 
                 5.5 
                 — 
                 — 
                 — 
               
               
                   
                 ANK repeat and PH domain 
               
               
                 Q96HE7_C37 
                 ERO1L ERO1-like protein alpha 
                 347 
                 — 
                 5.4 
                 — 
                 20.0  
               
               
                 Q07065_C100 
                 CKAP4 Cytoskeleton-associated protein 4 
                 733 
                 — 
                 — 
                 — 
                 15.4  
               
               
                 Q9BRJ7_C88 
                 NUDT16L1 Protein syndesmos 
                 432 
                 20.0  
                 20.0  
                 — 
                 — 
               
               
                 O75439_C265 
                 PMPCB Mitochondrial-processing peptidase 
                 320 
                 — 
                 — 
                 — 
                 — 
               
               
                   
                 subunit beta 
               
               
                 O43175_C369 
                 PHGDH D-3-phosphoglycerate 
                 248 
                 20.0  
                 — 
                 — 
                 — 
               
               
                   
                 dehydrogenase 
               
               
                 Q9UNI6_C265 
                 DUSP12 Dual specificity protein 
                 241 
                 — 
                 0.8 
                 — 
                 — 
               
               
                   
                 phosphatase 12 
               
               
                 Q06203_C100 
                 PPAT Amidophosphoribosyltransferase 
                 188 
                 — 
                 1.7 
                 — 
                 — 
               
               
                 A0AVT1_C347 
                 UBA6 Ubiquitin-like modifier-activating 
                 158 
                 — 
                 20.0  
                 — 
                 3.3 
               
               
                   
                 enzyme 6 
               
               
                 Q86X76_C203 
                 NIT1 Nitrilase homolog 1 
                 471 
                 — 
                 0.7 
                 — 
                 — 
               
               
                 Q6XZF7_C691 
                 DNMBP Dynamin-binding protein 
                 353 
                 — 
                 1.2 
                 — 
                 3.4 
               
               
                 Q15398_C129 
                 DLGAP5 Disks large-associated protein 5 
                 167 
                 20.0  
                 — 
                 — 
                 — 
               
               
                 O75717_C773 
                 WDHD1 WD repeat and HMG-box DNA- 
                 289 
                 — 
                 — 
                 4.2 
                 — 
               
               
                   
                 binding protein 1 
               
               
                 Q01433_C107 
                 AMPD2 AMP deaminase 2 
                 259 
                 4.4 
                 2.3 
                 6.2 
                 3.1 
               
               
                 Q8WVV9_C464 
                 HNRPLL Heterogeneous nuclear 
                 487 
                 — 
                 — 
                 — 
                 — 
               
               
                   
                 ribonucleoprotein L-like 
               
               
                 O14733_C131 
                 MAP2K7 Dual specificity mitogen-activated 
                 427 
                 — 
                 — 
                 — 
                 — 
               
               
                   
                 protein kinase 
               
               
                 Q14137_C404 
                 BOP1 Ribosome biogenesis protein BOP1 
                 535 
                 20.0  
                 1.2 
                 — 
                 — 
               
               
                 Q96RU2_C171 
                 USP28 Ubiquitin carboxyl-terminal 
                 569 
                 — 
                 20.0  
                 1.2 
                 — 
               
               
                   
                 hydrolase 28 
               
               
                 Q9Y679_C391 
                 AUP1 Ancient ubiquitous protein 1 
                 564 
                 — 
                 20.0  
                 20.0  
                 — 
               
               
                 P51610_C1872 
                 HCFC1 Host cell factor 1 
                 270 
                 4.1 
                 — 
                 — 
                 — 
               
               
                 P22307_C307 
                 SCP2 Non-specific lipid-transfer protein 
                 541 
                 20.0  
                 20.0  
                 20.0  
                 — 
               
               
                 Q9BTE3_C325 
                 MCMBP Mini-chromosome maintenance 
                 792 
                 — 
                 — 
                 — 
                 — 
               
               
                   
                 complex-binding protein 
               
               
                 Q9HA64_C24 
                 FN3KRP Ketosamine-3-kinase 
                 106 
                 6.3 
                 20.0  
                 — 
                 20.0  
               
               
                 Q5TFE4_C119 
                 NT5DC1 5-nucleotidase domain-containing 
                 75 
                 — 
                 — 
                 — 
                 20.0  
               
               
                   
                 protein 1 
               
               
                 Q96N67_C2125 
                 DOCK7 Dedicator of cytokinesis protein 7 
                 408 
                 — 
                 4.1 
                 5.4 
                 — 
               
               
                 P52948_C1312 
                 NUP98 Nuclear pore complex protein Nup98- 
                 575 
                 — 
                 — 
                 — 
                 — 
               
               
                   
                 Nup96 
               
               
                 Q5UIP0_C2298 
                 RIF1 Telomere-associated protein RIF1 
                 607 
                 — 
                 20.0  
                 — 
                 — 
               
               
                 P51812_C436 
                 RPS6KA3 Ribosomal protein S6 kinase 
                 662 
                 — 
                 — 
                 — 
                 2.1 
               
               
                   
                 alpha-3 
               
               
                 Q92616_C1692 
                 GCN1L1 Translational activator GCN1 
                 174 
                 1.4 
                 — 
                 — 
                 — 
               
               
                 Q15345_C297 
                 LRRC41 Leucine-rich repeat-containing 
                 536 
                 — 
                 — 
                 — 
                 — 
               
               
                   
                 protein 41 
               
               
                 Q9NPH0_C267 
                 ACP6 Lysophosphatidic acid phosphatase 
                 329 
                 — 
                 20.0  
                 20.0  
                 — 
               
               
                   
                 type 6 
               
               
                 P04183_C66 
                 TK1 Thymidine kinase, cytosolic 
                 138 
                 — 
                 — 
                 2.3 
                 7.0 
               
               
                 P42166_C629 
                 TMPO Lamina-associated polypeptide 2, 
                 793 
                 4.4 
                 — 
                 1.7 
                 — 
               
               
                   
                 isoform alpha 
               
               
                 Q15013_C124 
                 MAD2L1BP MAD2L1-binding protein 
                 794 
                 — 
                 13.0  
                 5.4 
                 — 
               
               
                 Q9Y5Y2_C72 
                 NUBP2 Cytosolic Fe—S cluster assembly 
                 795 
                 5.3 
                 — 
                 — 
                 4.0 
               
               
                   
                 factor NUBP2 
               
               
                 O15446_C86 
                 CD3EAP DNA-directed RNA polymerase I 
                 796 
                 3.9 
                 — 
                 — 
                 — 
               
               
                   
                 subunit RPA34 
               
               
                 Q13630_C116 
                 TSTA3 GDP-L-fucose synthase 
                 797 
                 20.0  
                 — 
                 — 
                 1.9 
               
               
                 Q8IYQ7_C324 
                 THNSL1 Threonine synthase-like 1 
                 628 
                 — 
                 — 
                 20.0  
                 1.6 
               
               
                 P05091_C319 
                 ALDH2 Aldehyde dehydrogenase, 
                 318 
                 — 
                 20.0  
                 — 
                 — 
               
               
                   
                 mitochondrial 
               
               
                 Q29RF7_C532 
                 PDS5A Sister chromatid cohesion protein 
                 261 
                 — 
                 20.0  
                 — 
                 — 
               
               
                   
                 PDS5 homolog A 
               
               
                 Q9Y570_C381 
                 PPME1 Protein phosphatase methylesterase 1 
                 578 
                 12.6  
                 1.1 
                 — 
                 20.0  
               
               
                 Q14980_C961 
                 NUMA1 Nuclear mitotic apparatus protein 1 
                 429 
                 — 
                 — 
                 — 
                 — 
               
               
                 P53384_C235 
                 NUBP1 Cytosolic Fe—S cluster assembly 
                 552 
                 — 
                 0.6 
                 0.6 
                 6.8 
               
               
                   
                 factor NUBP1 
               
               
                 Q15003_C418 
                 NCAPH Condensin complex subunit 2 
                 258 
                 20.0  
                 2.0.0 
                 — 
                 — 
               
               
                 P53634_C258 
                 CTSC Dipeptidyl peptidase 1 
                 798 
                 0.9 
                 1.2 
                 — 
                 — 
               
               
                 Q8NFF5_C499 
                 FLAD1 FAD synthase 
                 750 
                 6.2 
                 — 
                 — 
                 — 
               
               
                 Q9ULA0_C144 
                 DNPEP Aspartyl aminopeptidase 
                 134 
                 — 
                 — 
                 — 
                 2.1 
               
               
                 P22307_C94 
                 SCP2 Non-specific lipid-transfer protein 
                 559 
                 — 
                 20.0  
                 — 
                 — 
               
               
                 O15294_C620 
                 OGT UDP-N-acetylglucosamine-peptide N- 
                 279 
                 — 
                 20.0  
                 — 
                 — 
               
               
                   
                 acetylglucosamine 
               
               
                 Q9Y5S2_C1517 
                 CDC42BPB Serine/threonine-protein kinase 
                 554 
                 20.0  
                 20.0  
                 — 
                 — 
               
               
                   
                 MRCK beta 
               
               
                 Q8TD19_C623 
                 NEK9 Serine/threonine-protein kinase Nek9 
                 393 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q8N2W9_C326 
                 PIAS4 E3 SUMO-protein ligase PIAS4 
                 625 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q13158_C98 
                 FADD Protein FADD 
                 799 
                 20.0  
                 — 
                 — 
                 — 
               
               
                 Q9UKX7_C151 
                 NUP50 Nuclear pore complex protein Nup50 
                 234 
                 6.1 
                 — 
                 — 
                 — 
               
               
                 Q6PCB5_C280 
                 RSBN1L Round spermatid basic protein 1- 
                 519 
                 — 
                 — 
                 — 
                 — 
               
               
                   
                 like protein 
               
               
                 P10398_C597 
                 ARAF Serine/threonine-protein kinase A-Raf 
                 505 
                 — 
                 — 
                 — 
                 5.0 
               
               
                 Q9UL40_C68 
                 ZNF346 Zinc finger protein 346 
                 706 
                 — 
                 — 
                 — 
                 — 
               
               
                 P46013_C903 
                 MKI67 Antigen KI-67 
                 595 
                 20.0  
                 — 
                 — 
                 — 
               
               
                 Q16667_C39 
                 CDKN3 Cyclin-dependent kinase inhibitor 3 
                 482 
                 — 
                 0.6 
                 — 
                 — 
               
               
                 O75150_C890 
                 RNF40 E3 ubiquitin-protein ligase BRE1B 
                 405 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q00610_C870 
                 CLTC Clathrin heavy chain 1 
                 113 
                 — 
                 2.1 
                 — 
                 2.8 
               
               
                 Q9Y5T5_C205 
                 USP16 Ubiquitin carboxyl-terminal hydrolase 
                 474 
                 7.9 
                 20.0  
                 — 
                 — 
               
               
                   
                 16 
               
               
                 O95881_C66 
                 TXNDC12 Thioredoxin domain-containing 
                 342 
                 — 
                 — 
                 — 
                 — 
               
               
                   
                 protein 12 
               
               
                 Q7Z5K2_C160 
                 WAPAL Wings apart-like protein homolog 
                 800 
                 20.0  
                 — 
                 — 
                 — 
               
               
                 P42166_C518 
                 TMPO Lamina-associated polypeptide 2, 
                 801 
                 — 
                 — 
                 — 
                 3.4 
               
               
                   
                 isoform alpha 
               
               
                 Q9Y2S7_C143 
                 POLDIP2 Polymerase delta-interacting 
                 574 
                 — 
                 — 
                 — 
                 2.3 
               
               
                   
                 protein 2 
               
               
                 E2QRD5_C183 
                 C15orf38-AP3S2 Protein C15orf38-AP3S2 
                 581 
                 — 
                 — 
                 — 
                 4.9 
               
               
                 O95833_C22 
                 CLIC3 Chloride intracellular channel 
                 531 
                 — 
                 — 
                 — 
                 20.0  
               
               
                   
                 protein 3 
               
               
                 O94953_C694 
                 KDM4B Lysine-specific demethylase 4B 
                 395 
                 20.0  
                 — 
                 — 
                 — 
               
               
                 O00541_C272 
                 PES1 Pescadillo homolog 
                 511 
                 — 
                 — 
                 — 
                 5.0 
               
               
                 Q9NXJ5_C149 
                 PGPEP1 Pyroglutamyl-peptidase 1 
                 587 
                 — 
                 20.0  
                 — 
                 — 
               
               
                 Q8N5L8_C131 
                 RPP25L Ribonuclease P protein subunit 
                 670 
                 — 
                 — 
                 — 
                 — 
               
               
                   
                 p25-like protein 
               
               
                 Q8IZ73_C246 
                 RPUSD2 RNA pseudouridylate synthase 
                 441 
                 — 
                 — 
                 — 
                 — 
               
               
                   
                 domain-containing protein 
               
               
                 Q99798_C385 
                 ACO2 Aconitate hydratase, mitochondrial 
                 685 
                 20.0  
                 1.0 
                 — 
                 — 
               
               
                 Q9GZR2_C382 
                 REXO4 RNA exonuclease 4 
                 621 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q13613_C117 
                 MTMR1 Myotubularin-related protein 1 
                 717 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q9NUI1_C22 
                 DECR2 Peroxisomal 2,4-dienoyl-CoA 
                 698 
                 — 
                 — 
                 — 
                 — 
               
               
                   
                 reductase 
               
               
                 Q02556_C306 
                 IRF8 Interferon regulatory factor 8 
                 513 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q9UPT9_C171 
                 USP22 Ubiquitin carboxyl-terminal 
                 802 
                 — 
                 — 
                 — 
                 — 
               
               
                   
                 hydrolase 22 
               
               
                 Q8N999_C302 
                 C12orf29 Uncharacterized protein C12orf29 
                 484 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q8IU81_C363 
                 IRF2BP1 Interferon regulatory factor 2- 
                 803 
                 — 
                 — 
                 — 
                 — 
               
               
                   
                 binding protein 1 
               
               
                 Q9C0I1_C152 
                 MTMR12 Myotubularin-related protein 12 
                 671 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q9P2X3_C195 
                 IMPACT Protein IMPACT 
                 678 
                 — 
                 20.0  
                 — 
                 — 
               
               
                 Q6QNY0_C168 
                 BLOC1S3 Biogenesis of lysosome-related 
                 411 
                 — 
                 — 
                 — 
                 — 
               
               
                   
                 organelles complex 
               
               
                 Q15796_C81 
                 SMAD2 Mothers against decapentaplegic 
                 561 
                 20.0  
                 — 
                 — 
                 — 
               
               
                   
                 homolog 2 
               
               
                 Q9NZB2_C531 
                 FAM120A Constitutive coactivator of PPAR- 
                 492 
                 — 
                 — 
                 — 
                 — 
               
               
                   
                 gamma-like protein 
               
               
                 Q9HB90_C377 
                 RRAGC Ras-related GTP-binding protein C 
                 417 
                 3.3 
                 — 
                 — 
                 4.3 
               
               
                 Q9BR61_C267 
                 ACBD6 Acyl-CoA-binding domain- 
                 472 
                 — 
                 — 
                 — 
                 — 
               
               
                   
                 containing protein 6 
               
               
                 P16455_C145 
                 MGMT Methylated-DNA-protein-cysteine 
                 470 
                 — 
                 — 
                 — 
                 — 
               
               
                   
                 methyltransferase 
               
               
                 Q86UV5_C39 
                 USP48 Ubiquitin carboxyl-terminal hydrolase 
                 381 
                 20.0  
                 — 
                 — 
                 — 
               
               
                   
                 48 
               
               
                 A2A288_C367 
                 ZC3H12D Probable ribonuclease ZC3H12D 
                 515 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q8NEC7_C140 
                 GSTCD Glutathione S-transferase C-terminal 
                 602 
                 — 
                 — 
                 — 
                 — 
               
               
                   
                 domain-containing protein 
               
               
                 Q6PJG6_C673 
                 BRAT1 BRCA1-associated ATM activator 1 
                 695 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q13232_C158 
                 NME3 Nucleoside diphosphate kinase 3 
                 653 
                 — 
                 — 
                 — 
                 2.7 
               
               
                 Q86X76_C165 
                 NIT1 Nitrilase homolog 1 
                 345 
                 — 
                 0.9 
                 — 
                 — 
               
               
                 P42695_C541 
                 NCAPD3 Condensin-2 complex subunit D3 
                 573 
                 — 
                 — 
                 — 
                 — 
               
               
                 P41226_C599 
                 UBA7 Ubiquitin-like modifier-activating 
                 702 
                 — 
                 — 
                 — 
                 — 
               
               
                   
                 enzyme 7 
               
               
                 Q99986_C50 
                 VRK1 Serine/threonine-protein kinase VRK1 
                 497 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q8WUM4_C90 
                 PDCD6IP Programmed cell death 6- 
                 527 
                 — 
                 — 
                 — 
                 — 
               
               
                   
                 interacting protein 
               
               
                 P29590_C213 
                 PML Protein PML 
                 477 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q9P0K7_C973 
                 RAI14 Ankycorbin 
                 638 
                 — 
                 8.7 
                 — 
                 — 
               
               
                 P53992_C78 
                 SEC24C Protein transport protein Sec24C 
                 498 
                 — 
                 — 
                 5.4 
                 — 
               
               
                 Q13867_C73 
                 BLMH Bleomycin hydrolase 
                 431 
                 — 
                 — 
                 — 
                 3.9 
               
               
                 Q8ND24_C655 
                 RNF214 RING finger protein 214 
                 451 
                 6.5 
                 — 
                 — 
                 4.0 
               
               
                 Q96EK_C48 
                 THAP11 THAP domain-containing protein 11 
                 538 
                 7.9 
                 — 
                 — 
                 — 
               
               
                 Q96IV0_C309 
                 NGLY1 Peptide-N(4)-(N-acetyl-beta- 
                 660 
                 — 
                 — 
                 — 
                 — 
               
               
                   
                 glucosaminyl)asparagin 
               
               
                 Q5T1V6_C414 
                 DDX59 Probable ATP-dependent RNA 
                 439 
                 — 
                 — 
                 — 
                 — 
               
               
                   
                 helicase DDX59 
               
               
                 Q9UHQ1_C99 
                 NARF Nuclear prelamin A recognition factor 
                 740 
                 — 
                 — 
                 — 
                 — 
               
               
                 O43396_C34 
                 TXNL1 Thioredoxin-like protein 1 
                 310 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q8IV53_C174 
                 DENND1C DENN domain-containing protein 
                 804 
                 — 
                 — 
                 — 
                 — 
               
               
                   
                 1C 
               
               
                 Q8N9T8_C673 
                 KRI1 Protein KI1 homolog 
                 563 
                 — 
                 — 
                 5.3 
                 — 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
               
             
               
                 TABLE 2B 
               
               
                   
               
             
            
               
                   
                 9_200 μM —   
                 10_200 μM —   
                 10_200 μM —   
                 11_100 μM —   
                 12_200 μM —   
               
               
                 Identifier 
                 insitu_ramos 
                 insitu_231 
                 insitu_ramos 
                 insitu_231 
                 insitu_231 
               
               
                   
               
               
                 P04406_C152 
                 1.1 
                 1.0 
                 0.9 
                 0.8 
                 0.9 
               
               
                 P61978_C132 
                 1.4 
                 5.6 
                 1.6 
                 0.9 
                 7.5 
               
               
                 Q13526_C113 
                 1.3 
                 2.0 
                 1.3 
                 0.7 
                 0.6 
               
               
                 P24752_C119 
                 4.3 
                 4.5 
                 1.5 
                 1.2 
                 4.1 
               
               
                 P24752_C413 
                 20.0 
                 7.8 
                 2.2 
                 1.2 
                 9.9 
               
               
                 Q9NUY8_C283 
                 1.5 
                 2.0 
                 — 
                 1.1 
                 2.9 
               
               
                 P13667_C206 
                 1.4 
                 3.8 
                 — 
                 4.1 
                 16.6 
               
               
                 P12268_C140 
                 1.1 
                 0.7 
                 0.9 
                 0.6 
                 1.2 
               
               
                 Q15365_C194 
                 1.5 
                 1.6 
                 2.0 
                 0.4 
                 1.3 
               
               
                 Q9NVC6_C649 
                 1.3 
                 2.3 
                 2.1 
                 0.8 
                 4.0 
               
               
                 P42166_C561 
                 2.1 
                 17.8 
                 — 
                 0.6 
                 16.1 
               
               
                 Q9Y696_C35 
                 1.6 
                 2.7 
                 1.6 
                 1.9 
                 20.0 
               
               
                 P10599_C32 
                 2.1 
                 3.8 
                 — 
                 13.0 
                 20.0 
               
               
                 P31943_C267 
                 1.5 
                 4.8 
                 2.5 
                 0.9 
                 5.0 
               
               
                 Q86SX6_C67 
                 14.0 
                 1.3 
                 1.1 
                 1.4 
                 1.6 
               
               
                 P15121_C299 
                 1.5 
                 20.0 
                 — 
                 0.7 
                 0.7 
               
               
                 P52597_C267 
                 1.6 
                 2.5 
                 2.4 
                 1.0 
                 6.8 
               
               
                 Q9ULV4_C420 
                 1.4 
                 3.4 
                 — 
                 0.9 
                 2.2 
               
               
                 P62888_C92 
                 2.4 
                 1.3 
                 4.5 
                 0.8 
                 1.1 
               
               
                 Q9NQR4_C153 
                 20.0 
                 20.0 
                 — 
                 3.7 
                 0.9 
               
               
                 P42765_C92 
                 1.2 
                 3.7 
                 1.1 
                 — 
                 20.0 
               
               
                 Q15084_C55 
                 1.4 
                 3.1 
                 — 
                 4.3 
                 15.4 
               
               
                 Q96HE7_C241 
                 1.8 
                 2.0 
                 — 
                 1.8 
                 16.4 
               
               
                 Q99439_C164 
                 1.3 
                 1.2 
                 1.3 
                 0.6 
                 0.9 
               
               
                 P25205_C119 
                 1.8 
                 2.3 
                 — 
                 0.7 
                 1.0 
               
               
                 Q9NS86_C187 
                 1.7 
                 6.3 
                 — 
                 0.8 
                 2.0 
               
               
                 Q15233_C145 
                 1.4 
                 — 
                 2.2 
                 1.2 
                 2.4 
               
               
                 Q9BRA2_C43 
                 5.4 
                 20.0 
                 — 
                 17.7 
                 20.0 
               
               
                 P35611_C68 
                 2.3 
                 1.9 
                 — 
                 0.9 
                 3.6 
               
               
                 O75521_C380 
                 1.1 
                 4.8 
                 — 
                 0.8 
                 1.9 
               
               
                 Q9BXW7_C392 
                 — 
                 20.0 
                 — 
                 1.1 
                 5.1 
               
               
                 P30101_C406 
                 1.6 
                 3.3 
                 1.4 
                 — 
                 20.0 
               
               
                 Q96AB3_C114 
                 3.7 
                 20.0 
                 — 
                 0.9 
                 1.6 
               
               
                 P13667_C555 
                 1.6 
                 3.3 
                 1.4 
                 — 
                 20.0 
               
               
                 Q09161_C44 
                 1.4 
                 12.4 
                 — 
                 1.1 
                 4.7 
               
               
                 P78417_C32 
                 20.0 
                 20.0 
                 20.0 
                 — 
                 20.0 
               
               
                 Q9ULW0_C536 
                 1.6 
                 17.6 
                 — 
                 1.4 
                 20.0 
               
               
                 Q9NRG0_C55 
                 2.5 
                 2.7 
                 — 
                 1.1 
                 20.0 
               
               
                 Q96T76_C848 
                 1.8 
                 2.5 
                 — 
                 — 
                 20.0 
               
               
                 Q8TAQ2_C145 
                 2.4 
                 — 
                 20.0 
                 7.6 
                 — 
               
               
                 Q9BVC5_C10 
                 1.4 
                 3.1 
                 — 
                 1.1 
                 2.9 
               
               
                 Q7Z2W4_C645 
                 1.3 
                 3.8 
                 — 
                 1.0 
                 3.3 
               
               
                 Q9BQ69_C186 
                 — 
                 2.4 
                 — 
                 1.0 
                 2.7 
               
               
                 Q16831_C162 
                 — 
                 7.3 
                 — 
                 0.8 
                 0.9 
               
               
                 P30101_C57 
                 1.5 
                 3.3 
                 — 
                 2.2 
                 20.0 
               
               
                 P12268_C331 
                 2.6 
                 — 
                 2.1 
                 1.0 
                 — 
               
               
                 O95571_C170 
                 1.8 
                 9.0 
                 — 
                 1.2 
                 6.3 
               
               
                 O00299_C24 
                 1.4 
                 5.0 
                 — 
                 2.5 
                 20.0 
               
               
                 O14879_C343 
                 — 
                 4.9 
                 — 
                 0.4 
                 3.5 
               
               
                 Q96CM8_C64 
                 20.0 
                 20.0 
                 — 
                 1.5 
                 17.9 
               
               
                 P51946_C244 
                 2.0 
                 1.7 
                 — 
                 1.3 
                 1.3 
               
               
                 P49588_C773 
                 2.0 
                 2.1 
                 1.7 
                 0.9 
                 0.9 
               
               
                 Q96RN5_C618 
                 — 
                 — 
                 — 
                 1.0 
                 20.0 
               
               
                 O15294_C758 
                 — 
                 2.3 
                 — 
                 1.0 
                 20.0 
               
               
                 P46734_C207 
                 1.8 
                 0.8 
                 — 
                 0.6 
                 0.7 
               
               
                 Q96S55_C272 
                 2.5 
                 1.2 
                 — 
                 — 
                 2.4 
               
               
                 O95229_C54 
                 — 
                 2.3 
                 — 
                 1.2 
                 20.0 
               
               
                 O60610_C1227 
                 — 
                 1.5 
                 1.4 
                 0.9 
                 0.8 
               
               
                 Q13428_C38 
                 1.7 
                 4.2 
                 — 
                 1.1 
                 4.7 
               
               
                 Q9Y277_C65 
                 0.8 
                 3.3 
                 2.5 
                 1.4 
                 3.9 
               
               
                 P57764_C268 
                 4.9 
                 — 
                 2.2 
                 0.7 
                 — 
               
               
                 Q9Y3A3_C134 
                 20.0 
                 1.9 
                 — 
                 1.8 
                 1.4 
               
               
                 Q02252_C317 
                 2.6 
                 1.5 
                 0.7 
                 0.9 
                 3.2 
               
               
                 Q9NYL9_C132 
                 — 
                 — 
                 — 
                 0.5 
                 0.6 
               
               
                 P83731_C6 
                 1.3 
                 0.4 
                 2.0 
                 0.5 
                 0.3 
               
               
                 O95336_C32 
                 2.6 
                 — 
                 — 
                 0.9 
                 20.0 
               
               
                 Q13155_C291 
                 — 
                 1.7 
                 — 
                 0.9 
                 1.1 
               
               
                 Q13418_C346 
                 — 
                 1.1 
                 8.3 
                 0.6 
                 0.6 
               
               
                 A6NDU8_C179 
                 3.7 
                 1.3 
                 — 
                 0.7 
                 — 
               
               
                 Q9UKF6_C498 
                 1.7 
                 20.0 
                 2.8 
                 1.3 
                 4.1 
               
               
                 Q96F86_C413 
                 4.0 
                 20.0 
                 20.0 
                 20.0 
                 — 
               
               
                 P42224_C492 
                 — 
                 20.0 
                 — 
                 0.7 
                 1.0 
               
               
                 P11216_C326 
                 — 
                 8.6 
                 — 
                 0.8 
                 3.9 
               
               
                 P21980_C277 
                 — 
                 0.6 
                 — 
                 0.6 
                 0.3 
               
               
                 Q9HAV7_C124 
                 3.8 
                 1.0 
                 — 
                 0.9 
                 1.1 
               
               
                 P24752_C126 
                 20.0 
                 5.9 
                 — 
                 1.2 
                 5.8 
               
               
                 Q9NQ88_C161 
                 2.0 
                 4.6 
                 2.1 
                 0.9 
                 — 
               
               
                 Q13155_C23 
                 1.6 
                 2.3 
                 — 
                 1.2 
                 1.6 
               
               
                 Q9NQW6_C712 
                 — 
                 11.2 
                 — 
                 0.9 
                 16.7 
               
               
                 P51649_C340 
                 1.5 
                 13.4 
                 20.0 
                 — 
                 20.0 
               
               
                 Q15021_C439 
                 — 
                 5.2 
                 — 
                 0.9 
                 6.7 
               
               
                 Q5T0N5_C69 
                 — 
                 2.0 
                 — 
                 1.3 
                 20.0 
               
               
                 P38606_C138 
                 — 
                 20.0 
                 — 
                 9.2 
                 20.0 
               
               
                 Q9HCC0_C216 
                 3.3 
                 2.3 
                 — 
                 1.9 
                 20.0 
               
               
                 Q9NQC3_C1101 
                 20.0 
                 20.0 
                 — 
                 1.1 
                 20.0 
               
               
                 P35754_C23 
                 5.7 
                 — 
                 13.0 
                 20.0 
                 20.0 
               
               
                 Q99757_C90 
                 — 
                 — 
                 — 
                 2.7 
                 5.0 
               
               
                 Q9Y3D0_C93 
                 2.1 
                 2.1 
                 — 
                 0.9 
                 — 
               
               
                 Q9UMS0_C213 
                 — 
                 20.0 
                 — 
                 — 
                 20.0 
               
               
                 Q9NXV6_C516 
                 13.8 
                 7.7 
                 — 
                 1.0 
                 3.3 
               
               
                 Q96RS6_C376 
                 1.7 
                 5.7 
                 — 
                 0.8 
                 1.1 
               
               
                 Q14997_C1840 
                 — 
                 20.0 
                 — 
                 — 
                 20.0 
               
               
                 P50570_C27 
                 1.4 
                 3.1 
                 — 
                 0.7 
                 0.7 
               
               
                 Q86YH6_C71 
                 6.6 
                 20.0 
                 — 
                 1.0 
                 20.0 
               
               
                 Q99497_C106 
                 2.6 
                 1.7 
                 — 
                 1.3 
                 3.0 
               
               
                 Q9UJW0_C258 
                 20.0 
                 20.0 
                 20.0 
                 20.0 
                 20.0 
               
               
                 Q9BUH6_C180 
                 — 
                 3.8 
                 — 
                 — 
                 1.4 
               
               
                 P24752_C196 
                 6.8 
                 5.1 
                 2.3 
                 1.1 
                 4.6 
               
               
                 Q13162_C51 
                 — 
                 2.0 
                 — 
                 0.9 
                 1.0 
               
               
                 Q9BTA9_C553 
                 2.1 
                 20.0 
                 — 
                 1.7 
                 — 
               
               
                 P48643_C253 
                 1.1 
                 — 
                 0.9 
                 0.6 
                 5.1 
               
               
                 O75362_C286 
                 1.8 
                 2.6 
                 — 
                 1.0 
                 20.0 
               
               
                 O60825_C158 
                 1.8 
                 0.7 
                 1.2 
                 — 
                 0.8 
               
               
                 Q8NBS9_C350 
                 1.8 
                 — 
                 1.4 
                 3.4 
                 9.4 
               
               
                 Q9NYL2_C22 
                 — 
                 1.2 
                 — 
                 0.7 
                 0.7 
               
               
                 P27707_C9 
                 1.5 
                 1.9 
                 1.7 
                 0.5 
                 1.4 
               
               
                 Q93009_C223 
                 20.0 
                 2.5 
                 — 
                 1.0 
                 3.1 
               
               
                 O14929_C101 
                 — 
                 20.0 
                 — 
                 0.8 
                 20.0 
               
               
                 Q9UPQ0_C140 
                 — 
                 3.9 
                 — 
                 1.0 
                 1.9 
               
               
                 Q96NY7_C487 
                 — 
                 3.2 
                 — 
                 3.1 
                 20.0 
               
               
                 Q9NQ88_C114 
                 1.4 
                 2.1 
                 — 
                 0.8 
                 — 
               
               
                 Q14790_C360 
                 3.2 
                 — 
                 5.8 
                 — 
                 — 
               
               
                 P04183_C230 
                 2.0 
                 1.3 
                 — 
                 — 
                 — 
               
               
                 P68366_C54 
                 1.8 
                 7.9 
                 2.8 
                 0.3 
                 — 
               
               
                 Q13428_C1298 
                 2.5 
                 5.9 
                 — 
                 0.8 
                 20.0 
               
               
                 Q5MNZ6_C63 
                 11.2 
                 3.6 
                 — 
                 0.9 
                 20.0 
               
               
                 O14980_C528 
                 1.8 
                 1.3 
                 0.7 
                 0.7 
                 — 
               
               
                 Q86W42_C35 
                 2.7 
                 — 
                 — 
                 1.3 
                 — 
               
               
                 Q9Y6G9_C51 
                 — 
                 4.9 
                 — 
                 — 
                 6.5 
               
               
                 Q9NY27_C22 
                 1.8 
                 — 
                 2.1 
                 2.3 
                 20.0 
               
               
                 Q8NFH5_C255 
                 1.9 
                 3.5 
                 — 
                 1.3 
                 12.4 
               
               
                 Q9Y676_C128 
                 1.3 
                 2.9 
                 — 
                 0.8 
                 1.4 
               
               
                 P35658_C728 
                 4.2 
                 20.0 
                 — 
                 0.8 
                 — 
               
               
                 Q9NTX5_C133 
                 — 
                 1.6 
                 — 
                 1.0 
                 1.2 
               
               
                 Q15118_C71 
                 — 
                 18.0 
                 2.7 
                 0.6 
                 — 
               
               
                 Q00765_C18 
                 — 
                 4.2 
                 — 
                 0.8 
                 20.0 
               
               
                 P22307_C71 
                 — 
                 8.3 
                 — 
                 2.0 
                 3.7 
               
               
                 O75521_C312 
                 — 
                 5.0 
                 — 
                 — 
                 4.2 
               
               
                 P49189_C288 
                 20.0 
                 20.0 
                 — 
                 — 
                 1.8 
               
               
                 Q5T440_C170 
                 2.4 
                 5.7 
                 — 
                 — 
                 — 
               
               
                 Q15084_C190 
                 1.6 
                 3.7 
                 — 
                 — 
                 20.0 
               
               
                 Q96C19_C172 
                 — 
                 2.4 
                 — 
                 0.9 
                 0.9 
               
               
                 P22061_C102 
                 1.3 
                 1.6 
                 — 
                 0.8 
                 5.8 
               
               
                 Q9NP73_C86 
                 — 
                 — 
                 — 
                 0.7 
                 — 
               
               
                 Q9BRF8_C54 
                 1.9 
                 3.8 
                 — 
                 1.0 
                 1.2 
               
               
                 Q6ICB0_C108 
                 — 
                 — 
                 — 
                 0.7 
                 — 
               
               
                 P29590_C389 
                 — 
                 7.9 
                 — 
                 0.5 
                 — 
               
               
                 P07858_C211 
                 — 
                 7.4 
                 — 
                 1.1 
                 — 
               
               
                 Q9NX18_C83 
                 — 
                 4.4 
                 — 
                 1.1 
                 20.0 
               
               
                 P46109_C249 
                 4.0 
                 20.0 
                 — 
                 — 
                 20.0 
               
               
                 P45984_C177 
                 3.8 
                 20.0 
                 — 
                 0.9 
                 2.1 
               
               
                 P19447_C342 
                 2.7 
                 20.0 
                 — 
                 0.7 
                 6.7 
               
               
                 P42166_C341 
                 1.5 
                 — 
                 — 
                 0.8 
                 — 
               
               
                 Q8N1F7_C522 
                 3.7 
                 — 
                 — 
                 — 
                 20.0 
               
               
                 Q86UY8_C276 
                 — 
                 5.8 
                 — 
                 1.4 
                 20.0 
               
               
                 Q8WWI1_C228 
                 1.4 
                 17.2 
                 — 
                 1.3 
                 20.0 
               
               
                 Q9NWA0_C139 
                 — 
                 2.9 
                 — 
                 — 
                 20.0 
               
               
                 P09110_C381 
                 0.9 
                 — 
                 — 
                 0.8 
                 4.5 
               
               
                 Q2NL82_C126 
                 — 
                 4.9 
                 — 
                 — 
                 20.0 
               
               
                 Q5JPI3_C308 
                 4.0 
                 — 
                 — 
                 1.0 
                 — 
               
               
                 P23919_C163 
                 2.4 
                 — 
                 — 
                 0.2 
                 — 
               
               
                 Q96EB1_C218 
                 3.7 
                 1.1 
                 — 
                 — 
                 — 
               
               
                 Q96FX7_C209 
                 16.1 
                 — 
                 — 
                 — 
                 20.0 
               
               
                 O14933_C98 
                 2.8 
                 20.0 
                 3.2 
                 — 
                 — 
               
               
                 Q29RF7_C242 
                 — 
                 — 
                 — 
                 0.9 
                 12.9 
               
               
                 Q96T76_C819 
                 4.0 
                 — 
                 3.0 
                 0.8 
                 — 
               
               
                 P23919_C117 
                 1.4 
                 0.4 
                 — 
                 — 
                 0.2 
               
               
                 Q15149_C4574 
                 — 
                 2.2 
                 — 
                 1.1 
                 — 
               
               
                 Q96RP9_C153 
                 2.8 
                 14.8 
                 — 
                 — 
                 20.0 
               
               
                 P04818_C199 
                 11.7 
                 1.5 
                 — 
                 — 
                 — 
               
               
                 P27708_C73 
                 2.2 
                 — 
                 — 
                 — 
                 — 
               
               
                 P55265_C1224 
                 — 
                 10.7 
                 — 
                 — 
                 — 
               
               
                 Q9Y3D2_C105 
                 — 
                 20.0 
                 — 
                 1.3 
                 20.0 
               
               
                 O00244_C12 
                 1.6 
                 2.1 
                 — 
                 0.7 
                 — 
               
               
                 Q8WV74_C207 
                 20.0 
                 — 
                 20.0 
                 — 
                 — 
               
               
                 Q9NRW3_C130 
                 6.2 
                 — 
                 — 
                 — 
                 — 
               
               
                 P24468_C326 
                 — 
                 20.0 
                 — 
                 0.9 
                 — 
               
               
                 P42166_C684 
                 — 
                 5.2 
                 — 
                 0.7 
                 — 
               
               
                 Q96EY5_C231 
                 2.1 
                 — 
                 — 
                 0.7 
                 — 
               
               
                 P14635_C238 
                 2.1 
                 6.7 
                 — 
                 0.7 
                 — 
               
               
                 Q8NDH3_C81 
                 — 
                 5.7 
                 — 
                 — 
                 20.0 
               
               
                 Q9P0J1_C149 
                 — 
                 18.0 
                 — 
                 1.4 
                 18.5 
               
               
                 Q96P48_C900 
                 — 
                 1.8 
                 — 
                 — 
                 1.9 
               
               
                 Q96HE7_C37 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q07065_C100 
                 — 
                 — 
                 — 
                 1.0 
                 20.0 
               
               
                 Q9BRJ7_C88 
                 4.0 
                 20.0 
                 — 
                 — 
                 — 
               
               
                 O75439_C265 
                 1.7 
                 — 
                 2.1 
                 1.0 
                 — 
               
               
                 O43175_C369 
                 2.0 
                 — 
                 2.4 
                 — 
                 — 
               
               
                 Q9UNI6_C265 
                 — 
                 1.2 
                 — 
                 — 
                 1.2 
               
               
                 Q06203_C100 
                 2.9 
                 — 
                 20.0 
                 — 
                 — 
               
               
                 A0AVT1_C347 
                 2.6 
                 — 
                 20.0 
                 1.6 
                 — 
               
               
                 Q86X76_C203 
                 20.0 
                 — 
                 — 
                 0.8 
                 3.9 
               
               
                 Q6XZF7_C691 
                 10.0 
                 20.0 
                 20.0 
                 — 
                 — 
               
               
                 Q15398_C129 
                 — 
                 — 
                 — 
                 0.6 
                 — 
               
               
                 O75717_C773 
                 — 
                 2.2 
                 — 
                 1.2 
                 — 
               
               
                 Q01433_C107 
                 1.4 
                 — 
                 — 
                 0.6 
                 — 
               
               
                 Q8WVV9_C464 
                 — 
                 — 
                 — 
                 0.9 
                 2.0.0 
               
               
                 O14733_C131 
                 — 
                 1.8 
                 — 
                 — 
                 1.7 
               
               
                 Q14137_C404 
                 2.1 
                 20.0 
                 — 
                 — 
                 — 
               
               
                 Q96RU2_C171 
                 — 
                 — 
                 — 
                 2.2 
                 20.0 
               
               
                 Q9Y679_C391 
                 — 
                 — 
                 — 
                 3.0 
                 — 
               
               
                 P51610_C1872 
                 1.0 
                 1.5 
                 — 
                 0.5 
                 — 
               
               
                 P22307_C307 
                 — 
                 — 
                 — 
                 2.9 
                 20.0 
               
               
                 Q9BTE3_C325 
                 5.4 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q9HA64_C24 
                 1.6 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q5TFE4_C119 
                 20.0 
                 — 
                 20.0 
                 — 
                 — 
               
               
                 Q96N67_C2125 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 P52948_C1312 
                 — 
                 20.0 
                 — 
                 — 
                 20.0 
               
               
                 Q5UIP0_C2298 
                 — 
                 20.0 
                 — 
                 1.3 
                 — 
               
               
                 P51812_C436 
                 1.8 
                 — 
                 — 
                 0.5 
                 1.4 
               
               
                 Q92616_C1692 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q15345_C297 
                 — 
                 — 
                 — 
                 1.1 
                 — 
               
               
                 Q9NPH0_C267 
                 2.6 
                 13.4 
                 — 
                 — 
                 — 
               
               
                 P04183_C66 
                 1.8 
                 — 
                 — 
                 0.6 
                 — 
               
               
                 P42166_C629 
                 — 
                 2.5 
                 — 
                 0.6 
                 — 
               
               
                 Q15013_C124 
                 — 
                 — 
                 — 
                 1.0 
                 — 
               
               
                 Q9Y5Y2_C72 
                 1.3 
                 1.3 
                 — 
                 0.5 
                 — 
               
               
                 O15446_C86 
                 — 
                 4.7 
                 — 
                 — 
                 3.3 
               
               
                 Q13630_C116 
                 1.6 
                 20.0 
                 — 
                 — 
                 — 
               
               
                 Q8IYQ7_C324 
                 — 
                 5.3 
                 — 
                 — 
                 — 
               
               
                 P05091_C319 
                 20.0 
                 — 
                 — 
                 — 
                 20.0 
               
               
                 Q29RF7_C532 
                 — 
                 20.0 
                 — 
                 — 
                 — 
               
               
                 Q9Y570_C381 
                 — 
                 4.7 
                 — 
                 — 
                 — 
               
               
                 Q14980_C961 
                 — 
                 — 
                 — 
                 — 
                 20.0 
               
               
                 P53384_C235 
                 — 
                 — 
                 — 
                 0.5 
                 — 
               
               
                 Q15003_C418 
                 2.5 
                 — 
                 — 
                 1.6 
                 — 
               
               
                 P53634_C258 
                 — 
                 5.5 
                 — 
                 — 
                 13.4 
               
               
                 Q8NFF5_C499 
                 12.1 
                 — 
                 — 
                 1.6 
                 — 
               
               
                 Q9ULA0_C144 
                 1.3 
                 5.2 
                 — 
                 — 
                 — 
               
               
                 P22307_C94 
                 — 
                 — 
                 — 
                 3.3 
                 20.0 
               
               
                 O15294_C620 
                 — 
                 — 
                 12.0 
                 — 
                 — 
               
               
                 Q9Y5S2_C1517 
                 — 
                 — 
                 — 
                 1.2 
                 — 
               
               
                 Q8TD19_C623 
                 20.0 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q8N2W9_C326 
                 2.6 
                 4.5 
                 — 
                 — 
                 — 
               
               
                 Q13158_C98 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q9UKX7_C151 
                 1.8 
                 — 
                 — 
                 1.0 
                 6.7 
               
               
                 Q6PCB5_C280 
                 2.5 
                 — 
                 — 
                 — 
                 20.0 
               
               
                 P10398_C597 
                 1.3 
                 1.4 
                 — 
                 — 
                 — 
               
               
                 Q9UL40_C68 
                 20.0 
                 — 
                 — 
                 — 
                 20.0 
               
               
                 P46013_C903 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q16667_C39 
                 4.5 
                 2.3 
                 — 
                 — 
                 — 
               
               
                 O75150_C890 
                 — 
                 4.2 
                 — 
                 1.1 
                 — 
               
               
                 Q00610_C870 
                 — 
                 — 
                 — 
                 0.9 
                 1.7 
               
               
                 Q9Y5T5_C205 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 O95881_C66 
                 20.0 
                 — 
                 — 
                 — 
                 20.0 
               
               
                 Q7Z5K2_C160 
                 — 
                 20.0 
                 — 
                 1.0 
                 — 
               
               
                 P42166_C518 
                 1.3 
                 4.2 
                 — 
                 0.8 
                 — 
               
               
                 Q9Y2S7_C143 
                 — 
                 13.9 
                 — 
                 — 
                 — 
               
               
                 E2QRD5_C183 
                 — 
                 — 
                 — 
                 0.9 
                 — 
               
               
                 O95833_C22 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 O94953_C694 
                 4.2 
                 — 
                 3.9 
                 — 
                 — 
               
               
                 O00541_C272 
                 — 
                 — 
                 — 
                 1.0 
                 — 
               
               
                 Q9NXJ5_C149 
                 20.0 
                 — 
                 11.0 
                 — 
                 3.9 
               
               
                 Q8N5L8_C131 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q8IZ73_C246 
                 6.5 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q99798_C385 
                 — 
                 0.7 
                 — 
                 — 
                 — 
               
               
                 Q9GZR2_C382 
                 1.0 
                 — 
                 — 
                 — 
                 20.0 
               
               
                 Q13613_C117 
                 4.3 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q9NUI1_C22 
                 — 
                 — 
                 — 
                 2.1 
                 — 
               
               
                 Q02556_C306 
                 5.5 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q9UPT9_C171 
                 4.4 
                 — 
                 9.3 
                 0.8 
                 — 
               
               
                 Q8N999_C302 
                 20.0 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q8IU81_C363 
                 — 
                 5.9 
                 — 
                 — 
                 — 
               
               
                 Q9C0I1_C152 
                 — 
                 — 
                 — 
                 — 
                 20.0 
               
               
                 Q9P2X3_C195 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q6QNY0_C168 
                 4.6 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q15796_C81 
                 5.6 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q9NZB2_C531 
                 — 
                 — 
                 — 
                 — 
                 20.0 
               
               
                 Q9HB90_C377 
                 20.0 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q9BR61_C267 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 P16455_C145 
                 20.0 
                 — 
                 20.0 
                 — 
                 — 
               
               
                 Q86UV5_C39 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 A2A288_C367 
                 5.2 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q8NEC7_C140 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q6PJG6_C673 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q13232_C158 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q86X76_C165 
                 20.0 
                 — 
                 — 
                 — 
                 — 
               
               
                 P42695_C541 
                 — 
                 20.0 
                 6.5 
                 — 
                 — 
               
               
                 P41226_C599 
                 20.0 
                 8.0 
                 — 
                 — 
                 — 
               
               
                 Q99986_C50 
                 — 
                 — 
                 0.7 
                 — 
                 — 
               
               
                 Q8WUM4_C90 
                 5.0 
                 — 
                 — 
                 — 
                 — 
               
               
                 P29590_C213 
                 4.5 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q9P0K7_C973 
                 — 
                 — 
                 — 
                 0.8 
                 — 
               
               
                 P53992_C78 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q13867_C73 
                 — 
                 4.2 
                 — 
                 — 
                 — 
               
               
                 Q8ND24_C655 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q96EK4_C48 
                 2.3 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q96IV0_C309 
                 6.8 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q5T1V6_C414 
                 3.7 
                 11.3 
                 — 
                 — 
                 — 
               
               
                 Q9UHQ1_C99 
                 20.0 
                 — 
                 — 
                 — 
                 — 
               
               
                 O43396_C34 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q8IV53_C174 
                 — 
                 — 
                 5.0 
                 — 
                 — 
               
               
                 Q8N9T8_C673 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                   
               
               
                   
                 13_200 μM —   
                 13_200 μM —   
                 14_200 μM —   
                 14_200 μM —   
                 21_200 μM —   
               
               
                 Identifier 
                 insitu_231 
                 insitu_ramos 
                 insitu_231 
                 insitu_ramos 
                 insitu_231 
               
               
                   
               
               
                 P04406_C152 
                 0.9 
                 0.9 
                 0.9 
                 0.6 
                 1.3 
               
               
                 P61978_C132 
                 1.1 
                 1.1 
                 1.3 
                 0.9 
                 1.4 
               
               
                 Q13526_C113 
                 0.9 
                 1.0 
                 0.8 
                 1.0 
                 0.7 
               
               
                 P24752_C119 
                 2.1 
                 2.8 
                 1.0 
                 — 
                 1.6 
               
               
                 P24752_C413 
                 3.5 
                 20.0 
                 0.9 
                 0.8 
                 1.5 
               
               
                 Q9NUY8_C283 
                 1.1 
                 1.1 
                 0.8 
                 0.6 
                 0.8 
               
               
                 P13667_C206 
                 1.1 
                 — 
                 1.0 
                 0.7 
                 0.8 
               
               
                 P12268_C140 
                 0.7 
                 — 
                 10.3 
                 — 
                 0.6 
               
               
                 Q15365_C194 
                 0.9 
                 1.4 
                 1.0 
                 — 
                 1.1 
               
               
                 Q9NVC6_C649 
                 1.1 
                 1.0 
                 1.0 
                 1.4 
                 0.8 
               
               
                 P42166_C561 
                 1.2 
                 1.0 
                 2.9 
                 — 
                 1.4 
               
               
                 Q9Y696_C35 
                 2.3 
                 3.2 
                 0.7 
                 — 
                 1.1 
               
               
                 P10599_C32 
                 7.9 
                 4.1 
                 3.1 
                 — 
                 3.9 
               
               
                 P31943_C267 
                 1.1 
                 1.2 
                 1.3 
                 — 
                 1.5 
               
               
                 Q86SX6_C67 
                 10.3 
                 12.4 
                 3.1 
                 — 
                 1.4 
               
               
                 P15121_C299 
                 — 
                 0.8 
                 0.9 
                 — 
                 2.7 
               
               
                 P52597_C267 
                 1.2 
                 1.3 
                 1.5 
                 — 
                 1.5 
               
               
                 Q9ULV4_C420 
                 1.1 
                 1.1 
                 1.4 
                 — 
                 1.3 
               
               
                 P62888_C92 
                 0.8 
                 2.0 
                 1.0 
                 — 
                 0.9 
               
               
                 Q9NQR4_C153 
                 6.2 
                 12.2 
                 0.8 
                 — 
                 0.9 
               
               
                 P42765_C92 
                 — 
                 2.2 
                 1.2 
                 0.8 
                 1.3 
               
               
                 Q15084_C55 
                 — 
                 1.5 
                 1.0 
                 — 
                 0.9 
               
               
                 Q96HE7_C241 
                 1.5 
                 1.3 
                 1.1 
                 — 
                 1.6 
               
               
                 Q99439_C164 
                 0.9 
                 1.3 
                 0.9 
                 — 
                 0.9 
               
               
                 P25205_C119 
                 1.1 
                 1.3 
                 1.2 
                 — 
                 1.1 
               
               
                 Q9NS86_C187 
                 1.0 
                 1.1 
                 1.0 
                 3.3 
                 0.9 
               
               
                 Q15233_C145 
                 1.0 
                 1.1 
                 1.0 
                 — 
                 — 
               
               
                 Q9BRA2_C43 
                 20.0 
                 5.2 
                 1.4 
                 — 
                 16.0 
               
               
                 P35611_C68 
                 1.1 
                 1.0 
                 1.6 
                 — 
                 0.8 
               
               
                 O75521_C380 
                 1.0 
                 — 
                 1.1 
                 — 
                 1.8 
               
               
                 Q9BXW7_C392 
                 2.0 
                 — 
                 1.6 
                 1.1 
                 1.6 
               
               
                 P30101_C406 
                 — 
                 2.0 
                 1.1 
                 — 
                 — 
               
               
                 Q96AB3_C114 
                 2.4 
                 — 
                 1.0 
                 — 
                 4.9 
               
               
                 P13667_C555 
                 — 
                 2.0 
                 1.1 
                 — 
                 — 
               
               
                 Q09161_C44 
                 1.0 
                 — 
                 2.0 
                 — 
                 1.3 
               
               
                 P78417_C32 
                 20.0 
                 20.0 
                 1.7 
                 — 
                 — 
               
               
                 Q9ULW0_C536 
                 1.5 
                 — 
                 1.5 
                 — 
                 0.9 
               
               
                 Q9NRG0_C55 
                 1.2 
                 — 
                 1.7 
                 — 
                 — 
               
               
                 Q96T76_C848 
                 0.6 
                 1.5 
                 5.0 
                 20.0 
                 0.7 
               
               
                 Q8TAQ2_C145 
                 1.1 
                 — 
                 1.3 
                 — 
                 1.6 
               
               
                 Q9BVC5_C10 
                 1.6 
                 — 
                 1.2 
                 — 
                 1.5 
               
               
                 Q7Z2W4_C645 
                 1.3 
                 0.9 
                 1.4 
                 — 
                 0.9 
               
               
                 Q9BQ69_C186 
                 1.4 
                 — 
                 1.1 
                 — 
                 1.4 
               
               
                 Q16831_C162 
                 1.0 
                 — 
                 0.6 
                 — 
                 1.6 
               
               
                 P30101_C57 
                 — 
                 1.6 
                 1.0 
                 — 
                 1.0 
               
               
                 P12268_C331 
                 — 
                 1.4 
                 1.7 
                 — 
                 0.8 
               
               
                 O95571_C170 
                 1.2 
                 1.9 
                 1.0 
                 — 
                 1.7 
               
               
                 O00299_C24 
                 — 
                 1.8 
                 0.8 
                 — 
                 0.7 
               
               
                 O14879_C343 
                 1.0 
                 — 
                 1.5 
                 — 
                 0.8 
               
               
                 Q96CM8_C64 
                 1.4 
                 — 
                 1.5 
                 — 
                 2.0 
               
               
                 P51946_C244 
                 1.0 
                 1.2 
                 1.6 
                 — 
                 1.4 
               
               
                 P49588_C773 
                 0.8 
                 1.1 
                 1.0 
                 — 
                 1.1 
               
               
                 Q96RN5_C618 
                 1.0 
                 1.4 
                 1.6 
                 — 
                 1.0 
               
               
                 O15294_C758 
                 1.0 
                 — 
                 1.6 
                 2.9 
                 1.1 
               
               
                 P46734_C207 
                 0.8 
                 — 
                 13.8 
                 — 
                 0.9 
               
               
                 Q96S55_C272 
                 0.7 
                 — 
                 1.4 
                 — 
                 1.3 
               
               
                 O95229_C54 
                 0.8 
                 1.4 
                 5.0 
                 20.0 
                 0.8 
               
               
                 O60610_C1227 
                 0.7 
                 0.9 
                 — 
                 — 
                 20.0 
               
               
                 Q13428_C38 
                 1.6 
                 — 
                 3.6 
                 — 
                 1.5 
               
               
                 Q9Y277_C65 
                 1.0 
                 — 
                 1.7 
                 — 
                 2.9 
               
               
                 P57764_C268 
                 — 
                 1.5 
                 1.6 
                 — 
                 0.7 
               
               
                 Q9Y3A3_C134 
                 — 
                 1.9 
                 1.1 
                 — 
                 — 
               
               
                 Q02252_C317 
                 1.3 
                 — 
                 1.1 
                 — 
                 1.5 
               
               
                 Q9NYL9_C132 
                 — 
                 — 
                 0.5 
                 — 
                 1.4 
               
               
                 P83731_C6 
                 0.7 
                 1.0 
                 — 
                 — 
                 1.0 
               
               
                 O95336_C32 
                 1.6 
                 2.2 
                 3.2 
                 — 
                 0.9 
               
               
                 Q13155_C291 
                 — 
                 — 
                 1.6 
                 — 
                 0.8 
               
               
                 Q13418_C346 
                 0.7 
                 2.1 
                 0.8 
                 — 
                 0.5 
               
               
                 A6NDU8_C179 
                 0.8 
                 — 
                 1.9 
                 — 
                 0.9 
               
               
                 Q9UKF6_C498 
                 — 
                 1.4 
                 1.9 
                 — 
                 1.4 
               
               
                 Q96F86_C413 
                 1.6 
                 2.0 
                 1.0 
                 — 
                 0.8 
               
               
                 P42224_C492 
                 1.0 
                 — 
                 20.0 
                 — 
                 0.7 
               
               
                 P11216_C326 
                 1.3 
                 — 
                 0.8 
                 — 
                 0.9 
               
               
                 P21980_C277 
                 0.8 
                 — 
                 20.0 
                 — 
                 0.7 
               
               
                 Q9HAV7_C124 
                 — 
                 — 
                 1.3 
                 — 
                 1.7 
               
               
                 P24752_C126 
                 — 
                 — 
                 0.9 
                 — 
                 1.4 
               
               
                 Q9NQ88_C161 
                 1.1 
                 1.5 
                 20.0 
                 — 
                 1.0 
               
               
                 Q13155_C23 
                 0.9 
                 — 
                 1.1 
                 — 
                 0.9 
               
               
                 Q9NQW6_C712 
                 1.3 
                 — 
                 2.1 
                 — 
                 — 
               
               
                 P51649_C340 
                 1.1 
                 1.3 
                 0.7 
                 — 
                 1.2 
               
               
                 Q15021_C439 
                 — 
                 — 
                 5.9 
                 — 
                 0.7 
               
               
                 Q5T0N5_C69 
                 1.0 
                 — 
                 1.5 
                 — 
                 0.8 
               
               
                 P38606_C138 
                 20.0 
                 — 
                 1.9 
                 — 
                 20.0 
               
               
                 Q9HCC0_C216 
                 — 
                 1.8 
                 1.0 
                 — 
                 2.2 
               
               
                 Q9NQC3_C1101 
                 — 
                 — 
                 20.0 
                 — 
                 2.1 
               
               
                 P35754_C23 
                 — 
                 — 
                 0.7 
                 — 
                 — 
               
               
                 Q99757_C90 
                 — 
                 — 
                 3.2 
                 — 
                 4.3 
               
               
                 Q9Y3D0_C93 
                 — 
                 1.4 
                 2.7 
                 — 
                 0.5 
               
               
                 Q9UMS0_C213 
                 1.6 
                 — 
                 3.5 
                 — 
                 — 
               
               
                 Q9NXV6_C516 
                 2.4 
                 1.6 
                 1.4 
                 — 
                 0.8 
               
               
                 Q96RS6_C376 
                 0.7 
                 1.2 
                 0.9 
                 1.8 
                 1.4 
               
               
                 Q14997_C1840 
                 0.9 
                 1.6 
                 — 
                 20.0 
                 1.0 
               
               
                 P50570_C27 
                 — 
                 1.0 
                 1.0 
                 — 
                 0.8 
               
               
                 Q86YH6_C71 
                 1.2 
                 1.8 
                 20.0 
                 — 
                 2.1 
               
               
                 Q99497_C106 
                 — 
                 3.3 
                 0.8 
                 — 
                 — 
               
               
                 Q9UJW0_C258 
                 — 
                 1.9 
                 3.0 
                 — 
                 — 
               
               
                 Q9BUH6_C180 
                 1.1 
                 — 
                 1.3 
                 — 
                 — 
               
               
                 P24752_C196 
                 — 
                 — 
                 1.0 
                 — 
                 1.5 
               
               
                 Q13162_C51 
                 — 
                 — 
                 0.9 
                 — 
                 1.7 
               
               
                 Q9BTA9_C553 
                 1.4 
                 — 
                 1.7 
                 — 
                 2.8 
               
               
                 P48643_C253 
                 — 
                 — 
                 0.8 
                 — 
                 — 
               
               
                 O75362_C286 
                 1.1 
                 20.0 
                 1.4 
                 — 
                 1.1 
               
               
                 O60825_C158 
                 — 
                 0.9 
                 1.5 
                 14.2 
                 1.4 
               
               
                 Q8NBS9_C350 
                 1.3 
                 — 
                 1.0 
                 — 
                 — 
               
               
                 Q9NYL2_C22 
                 1.3 
                 — 
                 0.9 
                 — 
                 — 
               
               
                 P27707_C9 
                 1.0 
                 1.3 
                 — 
                 — 
                 1.3 
               
               
                 Q93009_C223 
                 — 
                 1.3 
                 1.1 
                 — 
                 1.8 
               
               
                 O14929_C101 
                 0.9 
                 1.2 
                 1.6 
                 1.9 
                 1.2 
               
               
                 Q9UPQ0_C140 
                 1.1 
                 — 
                 4.6 
                 — 
                 0.8 
               
               
                 Q96NY7_C487 
                 1.9 
                 — 
                 0.8 
                 — 
                 1.2 
               
               
                 Q9NQ88_C114 
                 1.1 
                 1.2 
                 2.2 
                 5.1 
                 0.9 
               
               
                 Q14790_C360 
                 1.2 
                 — 
                 — 
                 — 
                 0.9 
               
               
                 P04183_C230 
                 0.7 
                 — 
                 — 
                 — 
                 0.7 
               
               
                 P68366_C54 
                 — 
                 1.3 
                 — 
                 5.1 
                 0.8 
               
               
                 Q13428_C1298 
                 — 
                 — 
                 3.0 
                 — 
                 — 
               
               
                 Q5MNZ6_C63 
                 1.1 
                 — 
                 1.2 
                 — 
                 0.8 
               
               
                 O14980_C528 
                 1.1 
                 1.1 
                 20.0 
                 — 
                 0.8 
               
               
                 Q86W42_C35 
                 — 
                 — 
                 0.9 
                 — 
                 — 
               
               
                 Q9Y6G9_C51 
                 — 
                 1.5 
                 2.1 
                 4.3 
                 0.6 
               
               
                 Q9NY27_C22 
                 — 
                 1.5 
                 1.3 
                 — 
                 — 
               
               
                 Q8NFH5_C255 
                 1.5 
                 — 
                 1.0 
                 — 
                 1.8 
               
               
                 Q9Y676_C128 
                 — 
                 — 
                 1.2 
                 — 
                 1.5 
               
               
                 P35658_C728 
                 1.0 
                 — 
                 1.2 
                 — 
                 1.3 
               
               
                 Q9NTX5_C133 
                 1.1 
                 — 
                 1.0 
                 — 
                 1.1 
               
               
                 Q15118_C71 
                 1.6 
                 — 
                 4.4 
                 — 
                 1.7 
               
               
                 Q00765_C18 
                 1.2 
                 — 
                 20.0 
                 — 
                 0.7 
               
               
                 P22307_C71 
                 4.9 
                 — 
                 1.1 
                 — 
                 8.3 
               
               
                 O75521_C312 
                 0.7 
                 — 
                 1.4 
                 — 
                 1.6 
               
               
                 P49189_C288 
                 — 
                 12.0 
                 0.9 
                 — 
                 1.0 
               
               
                 Q5T440_C170 
                 1.2 
                 — 
                 1.2 
                 — 
                 1.6 
               
               
                 Q15084_C190 
                 — 
                 — 
                 1.1 
                 — 
                 — 
               
               
                 Q96C19_C172 
                 0.7 
                 — 
                 1.0 
                 — 
                 — 
               
               
                 P22061_C102 
                 0.9 
                 — 
                 1.0 
                 — 
                 — 
               
               
                 Q9NP73_C86 
                 0.9 
                 1.4 
                 1.1 
                 — 
                 — 
               
               
                 Q9BRF8_C54 
                 1.4 
                 — 
                 0.9 
                 — 
                 — 
               
               
                 Q6ICB0_C108 
                 — 
                 4.0 
                 — 
                 — 
                 0.6 
               
               
                 P29590_C389 
                 1.3 
                 — 
                 1.2 
                 — 
                 20.0 
               
               
                 P07858_C211 
                 1.6 
                 — 
                 1.0 
                 — 
                 2.6 
               
               
                 Q9NX18_C83 
                 — 
                 — 
                 2.2 
                 — 
                 1.3 
               
               
                 P46109_C249 
                 — 
                 1.8 
                 1.3 
                 — 
                 0.9 
               
               
                 P45984_C177 
                 — 
                 — 
                 1.5 
                 — 
                 — 
               
               
                 P19447_C342 
                 1.1 
                 — 
                 2.5 
                 — 
                 2.0 
               
               
                 P42166_C341 
                 1.3 
                 1.4 
                 2.3 
                 — 
                 1.7 
               
               
                 Q8N1F7_C522 
                 — 
                 2.2 
                 3.2 
                 20.0 
                 — 
               
               
                 Q86UY8_C276 
                 1.5 
                 — 
                 2.8 
                 — 
                 1.8 
               
               
                 Q8WWI1_C228 
                 2.0 
                 1.0 
                 — 
                 — 
                 1.1 
               
               
                 Q9NWA0_C139 
                 1.1 
                 — 
                 — 
                 — 
                 1.5 
               
               
                 P09110_C381 
                 — 
                 — 
                 1.0 
                 — 
                 — 
               
               
                 Q2NL82_C126 
                 — 
                 — 
                 0.8 
                 — 
                 1.5 
               
               
                 Q5JPI3_C308 
                 1.1 
                 1.7 
                 3.2 
                 — 
                 0.9 
               
               
                 P23919_C163 
                 — 
                 — 
                 0.9 
                 — 
                 — 
               
               
                 Q96EB1_C218 
                 1.2 
                 1.7 
                 — 
                 — 
                 0.7 
               
               
                 Q96FX7_C209 
                 2.1 
                 6.8 
                 2.7 
                 — 
                 2.0 
               
               
                 O14933_C98 
                 — 
                 — 
                 2.5 
                 — 
                 0.7 
               
               
                 Q29RF7_C242 
                 — 
                 — 
                 1.8 
                 — 
                 0.9 
               
               
                 Q96T76_C819 
                 — 
                 — 
                 3.4 
                 — 
                 — 
               
               
                 P23919_C117 
                 0.6 
                 — 
                 1.2 
                 — 
                 0.9 
               
               
                 Q15149_C4574 
                 1.4 
                 — 
                 1.2 
                 — 
                 1.0 
               
               
                 Q96RP9_C153 
                 — 
                 0.8 
                 1.2 
                 — 
                 1.4 
               
               
                 P04818_C199 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 P27708_C73 
                 — 
                 5.0 
                 20.0 
                 3.7 
                 0.6 
               
               
                 P55265_C1224 
                 1.9 
                 — 
                 4.2 
                 — 
                 2.2 
               
               
                 Q9Y3D2_C105 
                 — 
                 — 
                 2.7 
                 — 
                 — 
               
               
                 O00244_C12 
                 1.5 
                 — 
                 0.7 
                 — 
                 0.7 
               
               
                 Q8WV74_C207 
                 13.1 
                 — 
                 20.0 
                 — 
                 — 
               
               
                 Q9NRW3_C130 
                 — 
                 — 
                 — 
                 1.4 
                 1.3 
               
               
                 P24468_C326 
                 — 
                 — 
                 4.9 
                 — 
                 1.1 
               
               
                 P42166_C684 
                 1.2 
                 — 
                 3.1 
                 — 
                 — 
               
               
                 Q96EY5_C231 
                 — 
                 — 
                 — 
                 — 
                 0.7 
               
               
                 P14635_C238 
                 1.3 
                 1.5 
                 2.6 
                 — 
                 — 
               
               
                 Q8NDH3_C81 
                 — 
                 — 
                 1.4 
                 — 
                 1.6 
               
               
                 Q9P0J1_C149 
                 — 
                 — 
                 1.3 
                 — 
                 — 
               
               
                 Q96P48_C900 
                 1.2 
                 — 
                 — 
                 — 
                 0.7 
               
               
                 Q96HE7_C37 
                 — 
                 1.4 
                 1.4 
                 — 
                 — 
               
               
                 Q07065_C100 
                 1.6 
                 — 
                 11.2 
                 — 
                 2.2 
               
               
                 Q9BRJ7_C88 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 O75439_C265 
                 — 
                 — 
                 20.0 
                 — 
                 — 
               
               
                 O43175_C369 
                 — 
                 2.0 
                 — 
                 20.0 
                 1.0 
               
               
                 Q9UNI6_C265 
                 — 
                 — 
                 0.7 
                 — 
                 — 
               
               
                 Q06203_C100 
                 — 
                 2.0 
                 — 
                 — 
                 — 
               
               
                 A0AVT1_C347 
                 1.3 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q86X76_C203 
                 — 
                 — 
                 0.7 
                 — 
                 0.8 
               
               
                 Q6XZF7_C691 
                 1.6 
                 — 
                 — 
                 — 
                 0.8 
               
               
                 Q15398_C129 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 O75717_C773 
                 1.1 
                 — 
                 1.7 
                 — 
                 — 
               
               
                 Q01433_C107 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q8WVV9_C464 
                 — 
                 — 
                 2.2 
                 — 
                 1.4 
               
               
                 O14733_C131 
                 — 
                 1.6 
                 — 
                 20.0 
                 0.7 
               
               
                 Q14137_C404 
                 1.1 
                 — 
                 — 
                 — 
                 1.1 
               
               
                 Q96RU2_C171 
                 — 
                 — 
                 1.3 
                 — 
                 — 
               
               
                 Q9Y679_C391 
                 — 
                 — 
                 — 
                 — 
                 1.5 
               
               
                 P51610_C1872 
                 1.0 
                 — 
                 1.1 
                 — 
                 — 
               
               
                 P22307_C307 
                 — 
                 — 
                 0.9 
                 — 
                 20.0 
               
               
                 Q9BTE3_C325 
                 — 
                 — 
                 5.7 
                 — 
                 — 
               
               
                 Q9HA64_C24 
                 — 
                 — 
                 1.7 
                 — 
                 0.6 
               
               
                 Q5TFE4_C119 
                 — 
                 1.7 
                 3.8 
                 — 
                 1.2 
               
               
                 Q96N67_C2125 
                 — 
                 — 
                 1.8 
                 — 
                 — 
               
               
                 P52948_C1312 
                 1.2 
                 — 
                 1.7 
                 — 
                 1.1 
               
               
                 Q5UIP0_C2298 
                 — 
                 — 
                 20.0 
                 — 
                 0.9 
               
               
                 P51812_C436 
                 1.0 
                 — 
                 0.6 
                 — 
                 — 
               
               
                 Q92616_C1692 
                 — 
                 0.9 
                 20.0 
                 — 
                 — 
               
               
                 Q15345_C297 
                 1.6 
                 — 
                 5.8 
                 — 
                 1.1 
               
               
                 Q9NPH0_C267 
                 — 
                 — 
                 1.2 
                 — 
                 — 
               
               
                 P04183_C66 
                 1.0 
                 — 
                 — 
                 — 
                 — 
               
               
                 P42166_C629 
                 1.0 
                 — 
                 20.0 
                 — 
                 1.6 
               
               
                 Q15013_C124 
                 — 
                 — 
                 1.4 
                 — 
                 — 
               
               
                 Q9Y5Y2_C72 
                 — 
                 1.5 
                 — 
                 — 
                 — 
               
               
                 O15446_C86 
                 1.3 
                 — 
                 1.0 
                 — 
                 1.7 
               
               
                 Q13630_C116 
                 — 
                 1.2 
                 — 
                 — 
                 0.8 
               
               
                 Q8IYQ7_C324 
                 1.3 
                 — 
                 1.6 
                 — 
                 2.0 
               
               
                 P05091_C319 
                 — 
                 — 
                 3.3 
                 — 
                 — 
               
               
                 Q29RF7_C532 
                 — 
                 2.0 
                 2.5 
                 — 
                 — 
               
               
                 Q9Y570_C381 
                 0.9 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q14980_C961 
                 2.2 
                 — 
                 — 
                 — 
                 3.7 
               
               
                 P53384_C235 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q15003_C418 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 P53634_C258 
                 1.6 
                 — 
                 1.9 
                 — 
                 2.8 
               
               
                 Q8NFF5_C499 
                 — 
                 — 
                 20.0 
                 — 
                 — 
               
               
                 Q9ULA0_C144 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 P22307_C94 
                 — 
                 — 
                 1.0 
                 — 
                 — 
               
               
                 O15294_C620 
                 — 
                 — 
                 1.0 
                 — 
                 — 
               
               
                 Q9Y5S2_C1517 
                 — 
                 — 
                 0.9 
                 — 
                 — 
               
               
                 Q8TD19_C623 
                 — 
                 20.0 
                 — 
                 — 
                 0.8 
               
               
                 Q8N2W9_C326 
                 — 
                 20.0 
                 — 
                 — 
                 1.0 
               
               
                 Q13158_C98 
                 1.6 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q9UKX7_C151 
                 — 
                 — 
                 1.8 
                 — 
                 — 
               
               
                 Q6PCB5_C280 
                 — 
                 0.8 
                 20.0 
                 — 
                 — 
               
               
                 P10398_C597 
                 — 
                 1.0 
                 — 
                 — 
                 0.7 
               
               
                 Q9UL40_C68 
                 — 
                 20.0 
                 20.0 
                 — 
                 — 
               
               
                 P46013_C903 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q16667_C39 
                 — 
                 1.2 
                 — 
                 — 
                 0.8 
               
               
                 O75150_C890 
                 — 
                 — 
                 1.1 
                 — 
                 — 
               
               
                 Q00610_C870 
                 — 
                 — 
                 20.0 
                 — 
                 — 
               
               
                 Q9Y5T5_C205 
                 — 
                 20.0 
                 — 
                 — 
                 0.9 
               
               
                 O95881_C66 
                 20.0 
                 — 
                 1.3 
                 — 
                 — 
               
               
                 Q7Z5K2_C160 
                 — 
                 — 
                 2.4 
                 — 
                 — 
               
               
                 P42166_C518 
                 — 
                 — 
                 — 
                 — 
                 1.4 
               
               
                 Q9Y2S7_C143 
                 — 
                 — 
                 1.3 
                 — 
                 — 
               
               
                 E2QRD5_C183 
                 — 
                 — 
                 — 
                 — 
                 0.8 
               
               
                 O95833_C22 
                 — 
                 — 
                 0.8 
                 — 
                 1.0 
               
               
                 O94953_C694 
                 — 
                 1.5 
                 — 
                 — 
                 — 
               
               
                 O00541_C272 
                 1.4 
                 — 
                 3.8 
                 — 
                 — 
               
               
                 Q9NXJ5_C149 
                 — 
                 20.0 
                 — 
                 — 
                 — 
               
               
                 Q8N5L8_C131 
                 1.2 
                 — 
                 1.3 
                 — 
                 0.8 
               
               
                 Q8IZ73_C246 
                 — 
                 — 
                 — 
                 — 
                 1.8 
               
               
                 Q99798_C385 
                 — 
                 — 
                 — 
                 — 
                 2.0 
               
               
                 Q9GZR2_C382 
                 — 
                 0.9 
                 1.2 
                 — 
                 — 
               
               
                 Q13613_C117 
                 — 
                 — 
                 1.0 
                 1.7 
                 0.9 
               
               
                 Q9NUI1_C22 
                 — 
                 — 
                 1.1 
                 — 
                 — 
               
               
                 Q02556_C306 
                 — 
                 1.5 
                 — 
                 — 
                 — 
               
               
                 Q9UPT9_C171 
                 — 
                 3.2 
                 — 
                 — 
                 — 
               
               
                 Q8N999_C302 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q8IU81_C363 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q9C0I1_C152 
                 — 
                 6.5 
                 — 
                 — 
                 0.7 
               
               
                 Q9P2X3_C195 
                 — 
                 — 
                 1.6 
                 — 
                 — 
               
               
                 Q6QNY0_C168 
                 — 
                 1.2 
                 — 
                 — 
                 — 
               
               
                 Q15796_C81 
                 — 
                 — 
                 — 
                 — 
                 1.3 
               
               
                 Q9NZB2_C531 
                 — 
                 — 
                 — 
                 — 
                 1.6 
               
               
                 Q9HB90_C377 
                 — 
                 — 
                 1.1 
                 — 
                 — 
               
               
                 Q9BR61_C267 
                 1.1 
                 — 
                 — 
                 6.9 
                 — 
               
               
                 P16455_C145 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q86UV5_C39 
                 — 
                 — 
                 — 
                 — 
                 1.4 
               
               
                 A2A288_C367 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q8NEC7_C140 
                 1.8 
                 20.0 
                 — 
                 — 
                 — 
               
               
                 Q6PJG6_C673 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q13232_C158 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q86X76_C165 
                 — 
                 — 
                 0.8 
                 — 
                 — 
               
               
                 P42695_C541 
                 — 
                 — 
                 — 
                 — 
                 2.3 
               
               
                 P41226_C599 
                 — 
                 — 
                 — 
                 — 
                 1.0 
               
               
                 Q99986_C50 
                 — 
                 — 
                 1.6 
                 — 
                 — 
               
               
                 Q8WUM4_C90 
                 — 
                 — 
                 1.0 
                 — 
                 — 
               
               
                 P29590_C213 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q9P0K7_C973 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 P53992_C78 
                 0.7 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q13867_C73 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q8ND24_C655 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q96EK4_C48 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q96IV0_C309 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q5T1V6_C414 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q9UHQ1_C99 
                 — 
                 20.0 
                 — 
                 — 
                 — 
               
               
                 O43396_C34 
                 — 
                 — 
                 7.3 
                 — 
                 — 
               
               
                 Q8IV53_C174 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q8N9T8_C673 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
               
               
             
               
                 TABLE 2C 
               
               
                   
               
             
            
               
                   
                 27_200 μM —   
                 28_200 μM —   
                 29_200 μM —   
                 31_200 μM —   
                 31_200 μM —   
                 33_200 μM —   
               
               
                 Identifier 
                 insitu_231 
                 insitu_231 
                 insitu_ramos 
                 insitu_231 
                 insitu_ramos 
                 insitu_231 
               
               
                   
               
               
                 P04406_C152 
                 0.5 
                 0.8 
                 1.2 
                 0.8 
                 1.0 
                 1.1 
               
               
                 P61978_C132 
                 0.9 
                 1.0 
                 1.2 
                 0.9 
                 1.1 
                 1.3 
               
               
                 Q13526_C113 
                 0.5 
                 0.7 
                 1.0 
                 0.6 
                 1.1 
                 1.2 
               
               
                 P24752_C119 
                 1.6 
                 1.0 
                 1.2 
                 0.6 
                 0.7 
                 2.3 
               
               
                 P24752_C413 
                 1.9 
                 1.0 
                 1.2 
                 1.0 
                 — 
                 20.0 
               
               
                 Q9NUY8_C283 
                 0.6 
                 0.7 
                 1.3 
                 0.6 
                 — 
                 1.6 
               
               
                 P13667_C206 
                 1.0 
                 1.3 
                 1.4 
                 0.8 
                 1.1 
                 2.7 
               
               
                 P12268_C140 
                 0.5 
                 0.6 
                 1.6 
                 0.6 
                 1.0 
                 1.4 
               
               
                 Q15365_C194 
                 0.5 
                 — 
                 1.0 
                 0.7 
                 1.6 
                 2.2 
               
               
                 Q9NVC6_C649 
                 1.3 
                 1.1 
                 1.6 
                 0.8 
                 — 
                 1.2 
               
               
                 P42166_C561 
                 0.8 
                 1.1 
                 0.9 
                 1.3 
                 2.5 
                 2.9 
               
               
                 Q9Y696_C35 
                 1.0 
                 2.7 
                 1.0 
                 0.6 
                 — 
                 8.9 
               
               
                 P10599_C32 
                 2.5 
                 20.0 
                 1.9 
                 1.2 
                 1.7 
                 20.0 
               
               
                 P31943_C267 
                 1.1 
                 — 
                 1.4 
                 0.7 
                 0.9 
                 1.3 
               
               
                 Q86SX6_C67 
                 1.5 
                 — 
                 1.2 
                 — 
                 0.7 
                 1.0 
               
               
                 P15121_C299 
                 0.5 
                 0.8 
                 1.1 
                 0.8 
                 1.3 
                 0.7 
               
               
                 P52597_C267 
                 1.0 
                 — 
                 1.2 
                 1.2 
                 1.3 
                 1.6 
               
               
                 Q9ULV4_C420 
                 0.8 
                 0.7 
                 — 
                 0.8 
                 1.1 
                 1.6 
               
               
                 P62888_C92 
                 0.6 
                 0.9 
                 2.0 
                 — 
                 — 
                 1.1 
               
               
                 Q9NQR4_C153 
                 1.3 
                 — 
                 — 
                 0.6 
                 1.4 
                 1.0 
               
               
                 P42765_C92 
                 1.2 
                 — 
                 0.9 
                 0.8 
                 1.2 
                 1.3 
               
               
                 Q15084_C55 
                 1.2 
                 1.4 
                 1.0 
                 0.7 
                 — 
                 3.7 
               
               
                 Q96HE7_C241 
                 0.9 
                 1.1 
                 1.3 
                 0.7 
                 — 
                 2.3 
               
               
                 Q99439_C164 
                 — 
                 0.9 
                 1.0 
                 0.7 
                 1.3 
                 1.5 
               
               
                 P25205_C119 
                 1.0 
                 — 
                 1.3 
                 0.5 
                 — 
                 1.2 
               
               
                 Q9NS86_C187 
                 0.4 
                 — 
                 1.7 
                 0.5 
                 — 
                 1.5 
               
               
                 Q15233_C145 
                 1.2 
                 1.1 
                 — 
                 0.7 
                 0.8 
                 1.3 
               
               
                 Q9BRA2_C43 
                 20.0 
                 — 
                 2.3 
                 0.6 
                 — 
                 20.0 
               
               
                 P35611_C68 
                 0.9 
                 1.7 
                 — 
                 — 
                 — 
                 1.6 
               
               
                 O75521_C380 
                 1.6 
                 0.8 
                 1.2 
                 — 
                 — 
                 0.7 
               
               
                 Q9BXW7_C392 
                 1.3 
                 1.0 
                 1.5 
                 — 
                 — 
                 1.1 
               
               
                 P30101_C406 
                 1.2 
                 — 
                 1.5 
                 0.8 
                 1.1 
                 — 
               
               
                 Q96AB3_C114 
                 1.0 
                 0.8 
                 1.1 
                 0.7 
                 — 
                 0.9 
               
               
                 P13667_C555 
                 1.2 
                 — 
                 1.5 
                 0.8 
                 1.1 
                 — 
               
               
                 Q09161_C44 
                 0.8 
                 — 
                 1.1 
                 0.6 
                 — 
                 1.1 
               
               
                 P78417_C32 
                 20.0 
                 20.0 
                 20.0 
                 0.8 
                 2.6 
                 20.0 
               
               
                 Q9ULW0_C536 
                 1.1 
                 1.0 
                 1.8 
                 — 
                 — 
                 2.2 
               
               
                 Q9NRG0_C55 
                 0.9 
                 — 
                 1.5 
                 — 
                 1.6 
                 1.1 
               
               
                 Q96T76_C848 
                 0.5 
                 0.8 
                 1.0 
                 20.0 
                 — 
                 — 
               
               
                 Q8TAQ2_C145 
                 2.1 
                 0.9 
                   
                 0.8 
                 1.1 
                 1.3 
               
               
                 Q9BVC5_C10 
                 1.1 
                 0.9 
                 1.8 
                 — 
                 — 
                 1.3 
               
               
                 Q7Z2W4_C645 
                 0.8 
                 — 
                 1.6 
                 — 
                 — 
                 2.1 
               
               
                 Q9BQ69_C186 
                 2.4 
                 — 
                 1.5 
                 0.5 
                 — 
                 0.9 
               
               
                 Q16831_C162 
                 0.5 
                 0.7 
                 — 
                 — 
                 — 
                 1.3 
               
               
                 P30101_C57 
                 1.1 
                 1.6 
                 1.2 
                 0.9 
                 — 
                 — 
               
               
                 P12268_C331 
                 0.7 
                 0.8 
                 1.3 
                 1.0 
                 1.1 
                 1.5 
               
               
                 O95571_C170 
                 1.1 
                 — 
                 1.5 
                 — 
                 — 
                 1.2 
               
               
                 O00299_C24 
                 0.7 
                 — 
                 1.1 
                 0.6 
                 — 
                 8.4 
               
               
                 O14879_C343 
                 0.4 
                 0.7 
                 — 
                 0.9 
                 — 
                 2.4 
               
               
                 Q96CM8_C64 
                 1.8 
                 — 
                 2.3 
                 0.8 
                 — 
                 2.3 
               
               
                 P51946_C244 
                 1.1 
                 — 
                 1.1 
                 — 
                 — 
                 0.9 
               
               
                 P49588_C773 
                 0.6 
                 — 
                 1.1 
                 — 
                 1.2 
                 — 
               
               
                 Q96RN5_C618 
                 0.8 
                 0.7 
                 1.3 
                 0.9 
                 — 
                 2.0 
               
               
                 O15294_C758 
                 1.0 
                 1.0 
                 — 
                 — 
                 — 
                 1.2 
               
               
                 P46734_C207 
                 0.8 
                 — 
                 — 
                 — 
                 — 
                 1.2 
               
               
                 Q96S55_C272 
                 0.9 
                 0.5 
                 — 
                 — 
                 — 
                 1.2 
               
               
                 O95229_C54 
                 0.5 
                 0.7 
                 1.2 
                 — 
                 — 
                 — 
               
               
                 O60610_C1227 
                 0.5 
                 — 
                 1.6 
                 0.6 
                 1.2 
                 — 
               
               
                 Q13428_C38 
                 1.3 
                 1.0 
                 1.5 
                 — 
                 — 
                 — 
               
               
                 Q9Y277_C65 
                 1.6 
                 1.2 
                 — 
                 — 
                 1.0 
                 — 
               
               
                 P57764_C268 
                 0.6 
                 — 
                 1.1 
                 — 
                 3.1 
                 — 
               
               
                 Q9Y3A3_C134 
                 — 
                 — 
                 1.2 
                 1.0 
                 1.8 
                 1.2 
               
               
                 Q02252_C317 
                 2.0 
                 1.1 
                 1.2 
                 — 
                 — 
                 2.3 
               
               
                 Q9NYL9_C132 
                 0.6 
                 0.7 
                 0.9 
                 0.7 
                 0.7 
                 — 
               
               
                 P83731_C6 
                 0.4 
                 — 
                 1.6 
                 — 
                 — 
                 1.6 
               
               
                 O95336_C32 
                 0.5 
                 — 
                 3.0 
                 — 
                 1.7 
                 2.3 
               
               
                 O13155_C291 
                 0.7 
                 0.9 
                 — 
                 0.8 
                 — 
                 — 
               
               
                 Q13418_C346 
                 0.6 
                 — 
                 — 
                 0.6 
                 — 
                 1.4 
               
               
                 A6NDU8_C179 
                 0.7 
                 0.8 
                 1.0 
                 — 
                 — 
                 7.4 
               
               
                 Q9UKF6_C498 
                 1.5 
                 — 
                 2.3 
                 — 
                 — 
                 1.6 
               
               
                 Q96F86_C413 
                 0.7 
                 — 
                 1.9 
                 — 
                 1.3 
                 3.0 
               
               
                 P42224_C492 
                 — 
                 0.8 
                 3.8 
                 0.8 
                 1.9 
                 1.3 
               
               
                 P11216_C326 
                 0.7 
                 — 
                 — 
                 0.5 
                 — 
                 1.6 
               
               
                 P21980_C277 
                 0.6 
                 0.4 
                 — 
                 — 
                 — 
                 — 
               
               
                 O9HAV7_C124 
                 0.6 
                 — 
                 1.0 
                 — 
                 — 
                 — 
               
               
                 P24752_C126 
                 — 
                 1.2 
                 1.2 
                 0.7 
                 — 
                 20.0 
               
               
                 Q9NQ88_C161 
                 0.6 
                 — 
                 1.3 
                 1.0 
                 2.6 
                 — 
               
               
                 Q13155_C23 
                 0.7 
                 — 
                 1.6 
                 — 
                 — 
                 1.4 
               
               
                 Q9NQW6_C712 
                 1.0 
                 0.9 
                 — 
                 0.7 
                 — 
                 1.5 
               
               
                 P51649_C340 
                 0.9 
                 — 
                 1.0 
                 — 
                 1.0 
                 0.9 
               
               
                 Q15021_C439 
                 0.6 
                 0.9 
                 1.4 
                 2.0.0 
                 — 
                 — 
               
               
                 Q5T0N5_C69 
                 0.6 
                 — 
                 — 
                 — 
                 — 
                 2.6 
               
               
                 P38606_C138 
                 4.6 
                 — 
                 — 
                 — 
                 1.7 
                 20.0 
               
               
                 Q9HCC0_C216 
                 1.0 
                 — 
                 — 
                 — 
                 — 
                 1.0 
               
               
                 Q9NQC3_C1101 
                 1.4 
                 — 
                 — 
                 12.8 
                 — 
                 2.1 
               
               
                 P35754_C23 
                 0.7 
                 1.4 
                 — 
                 0.6 
                 1.1 
                 20.0 
               
               
                 Q99757_C90 
                 6.3 
                 — 
                 1.6 
                 1.4 
                 — 
                 — 
               
               
                 Q9Y3D0_C93 
                 0.7 
                 0.8 
                 1.0 
                 — 
                 — 
                 — 
               
               
                 Q9UMS0_C213 
                 1.3 
                 — 
                 2.0 
                 1.5 
                 — 
                 1.9 
               
               
                 Q9NXV6_C516 
                 1.4 
                 — 
                 1.1 
                 — 
                 — 
                 1.4 
               
               
                 Q96RS6_C376 
                 — 
                 — 
                 1.3 
                 0.8 
                 — 
                 — 
               
               
                 Q14997_C1840 
                 20.0 
                 0.9 
                 — 
                 — 
                 1.2 
                 — 
               
               
                 P50570_C27 
                 0.5 
                 — 
                 1.0 
                 — 
                 — 
                 — 
               
               
                 Q86YH6_C71 
                 1.3 
                 — 
                 1.1 
                 — 
                 — 
                 — 
               
               
                 Q99497_C106 
                 0.9 
                 1.0 
                 — 
                 0.8 
                 1.0 
                 — 
               
               
                 Q9UJW0_C258 
                 0.8 
                 — 
                 20.0 
                 — 
                 — 
                 — 
               
               
                 Q9BUH6_C180 
                 — 
                 1.1 
                 1.5 
                 0.8 
                 — 
                 1.4 
               
               
                 P24752_C196 
                 — 
                 — 
                 1.1 
                 — 
                 — 
                 3.4 
               
               
                 Q13162_C51 
                 0.9 
                 — 
                 — 
                 — 
                 1.3 
                 1.7 
               
               
                 Q9BTA9_C553 
                 — 
                 — 
                 1.1 
                 — 
                 — 
                 — 
               
               
                 P48643_C253 
                 — 
                 0.8 
                 — 
                 0.5 
                 1.0 
                 — 
               
               
                 O75362_C286 
                 1.0 
                 0.9 
                 1.0 
                 — 
                 — 
                 — 
               
               
                 O60825_C158 
                 — 
                 — 
                 0.9 
                 — 
                 1.3 
                 — 
               
               
                 Q8NBS9_C350 
                 1.1 
                 1.1 
                 — 
                 0.8 
                 — 
                 2.6 
               
               
                 Q9NYL2_C22 
                 0.7 
                 — 
                 1.2 
                 — 
                 — 
                 1.5 
               
               
                 P97707_C9 
                 — 
                 — 
                 1.2 
                 — 
                 1.2 
                 1.9 
               
               
                 Q93009_C223 
                 1.1 
                 1.0 
                 1.0 
                 — 
                 — 
                 — 
               
               
                 O14929_C101 
                 — 
                 — 
                 1.0 
                 — 
                 — 
                 1.3 
               
               
                 Q9UPQ0_C140 
                 0.7 
                 — 
                 — 
                 — 
                 — 
                 2.5 
               
               
                 Q96NY7_C487 
                 — 
                 — 
                 — 
                 0.5 
                 — 
                 14.9 
               
               
                 Q9NQ88_C114 
                 0.4 
                 — 
                 0.9 
                 — 
                 — 
                 — 
               
               
                 Q14790_C360 
                 0.4 
                 — 
                 1.6 
                 0.5 
                 — 
                 3.2 
               
               
                 P04183_C230 
                 — 
                 — 
                 1.2 
                 — 
                 2.1 
                 1.6 
               
               
                 P68366_C54 
                 0.3 
                 — 
                 1.0 
                 — 
                 1.1 
                 — 
               
               
                 Q13428_C1298 
                 1.0 
                 0.9 
                 — 
                 — 
                 2.2 
                 — 
               
               
                 Q5MNZ6_C63 
                 — 
                 1.7 
                 — 
                 — 
                 — 
                 1.6 
               
               
                 O14980_C528 
                 — 
                 — 
                 1.1 
                 — 
                 — 
                 — 
               
               
                 Q86W42_C35 
                 1.3 
                 1.3 
                 — 
                 0.5 
                 — 
                 1.6 
               
               
                 Q9Y6G9_C51 
                 0.6 
                 0.7 
                 — 
                 — 
                 1.6 
                 1.8 
               
               
                 Q9NY27_C22 
                 — 
                 — 
                 1.7 
                 — 
                 — 
                 — 
               
               
                 Q8NFN5_C255 
                 — 
                 — 
                 1.6 
                 — 
                 — 
                 — 
               
               
                 Q9Y676_C128 
                 1.0 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 P35658_C728 
                 — 
                 — 
                 1.7 
                 0.7 
                 — 
                 6.4 
               
               
                 Q9NTX5_C133 
                 1.5 
                 — 
                 — 
                 — 
                 — 
                 1.0 
               
               
                 Q15118_C71 
                 1.5 
                 — 
                 1.8 
                 — 
                 — 
                 — 
               
               
                 Q00765_C18 
                 1.1 
                 — 
                 1.4 
                 — 
                 — 
                 1.1 
               
               
                 P22307_C71 
                 20.0 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 O75521_C312 
                 1.1 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 P49189_C288 
                 — 
                 — 
                 — 
                 — 
                 — 
                 20.0 
               
               
                 Q5T440_C170 
                 — 
                 — 
                 1.3 
                 — 
                 — 
                 2.5 
               
               
                 Q15084_C190 
                 1.0 
                 — 
                 1.0 
                 1.0 
                 — 
                 — 
               
               
                 Q96C19_C172 
                 — 
                 — 
                 1.2 
                 1.6 
                 — 
                 — 
               
               
                 P22061_C102 
                 2.2 
                 — 
                 1.2 
                 — 
                 — 
                 — 
               
               
                 Q9NP73_C86 
                 0.4 
                 — 
                 2.0 
                 — 
                 — 
                 — 
               
               
                 Q9BRF8_C54 
                 — 
                 — 
                 1.5 
                 — 
                 — 
                 1.8 
               
               
                 Q6ICB0_C108 
                 1.9 
                 — 
                 1.0 
                 1.2 
                 1.3 
                 — 
               
               
                 P29590_C389 
                 0.5 
                 — 
                 — 
                 1.1 
                 — 
                 — 
               
               
                 P07858_C211 
                 0.8 
                 — 
                 — 
                 — 
                 — 
                 2.2 
               
               
                 Q9NX18_C83 
                 1.5 
                 — 
                 1.9 
                 — 
                 — 
                 — 
               
               
                 P46109_C249 
                 — 
                 — 
                 4.2 
                 — 
                 — 
                 — 
               
               
                 P45984_C177 
                 0.5 
                 — 
                 1.7 
                 — 
                 — 
                 2.0 
               
               
                 P19447_C342 
                 — 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 P42166_C341 
                 0.6 
                 — 
                 — 
                 — 
                 2.0 
                 — 
               
               
                 Q8N1F7_C522 
                 — 
                 — 
                 1.7 
                 — 
                 3.6 
                 1.7 
               
               
                 Q86UY8_C276 
                 1.7 
                 — 
                 — 
                 — 
                 — 
                 0.8 
               
               
                 Q8WWI1_C228 
                 0.8 
                 — 
                 1.0 
                 — 
                 — 
                 — 
               
               
                 Q9NWA0_C139 
                 1.3 
                 — 
                 0.7 
                 — 
                 — 
                 1.6 
               
               
                 P09110_C381 
                 — 
                 0.8 
                 — 
                 0.7 
                 — 
                 — 
               
               
                 Q2NL82_C126 
                 0.4 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q5JPI3_C308 
                 0.7 
                 — 
                 1.3 
                 — 
                 — 
                 — 
               
               
                 P23919_C163 
                 0.2 
                 0.4 
                 — 
                 — 
                 1.0 
                 — 
               
               
                 Q96EB1_C218 
                 0.6 
                 — 
                 1.1 
                 — 
                 — 
                 — 
               
               
                 Q96FX7_C209 
                 — 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 O14933_C98 
                 — 
                 — 
                 2.4 
                 — 
                 1.9 
                 — 
               
               
                 Q29RF7_C242 
                 0.9 
                 1.0 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q96T76_C819 
                 0.5 
                 — 
                 — 
                 20.0 
                 20.0 
                 — 
               
               
                 P23919_C117 
                 — 
                 — 
                 1.6 
                 — 
                 — 
                 2.5 
               
               
                 Q15149_C4574 
                 1.3 
                 — 
                 — 
                 — 
                 — 
                 1.4 
               
               
                 Q96RP9_C153 
                 1.6 
                 — 
                 1.2 
                 — 
                 — 
                 — 
               
               
                 P04818_C199 
                 0.5 
                 — 
                 2.5 
                 — 
                 — 
                 — 
               
               
                 P27708_C73 
                 0.5 
                 — 
                 1.8 
                 — 
                 — 
                 — 
               
               
                 P55265_C1224 
                 1.4 
                 — 
                 1.8 
                 — 
                 — 
                 1.6 
               
               
                 Q9Y3D2_C105 
                 1.5 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 O00244_C12 
                 0.4 
                 — 
                 1.4 
                 — 
                 — 
                 1.8 
               
               
                 Q8WV74_C207 
                 2.2 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q9NRW3_C130 
                 1.3 
                 — 
                 13.3 
                 — 
                 — 
                 — 
               
               
                 P24468_C326 
                 1.2 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 P42166_C684 
                 — 
                 — 
                 — 
                 — 
                 3.3 
                 — 
               
               
                 Q96EY5_C231 
                 0.6 
                 — 
                 1.1 
                 — 
                 — 
                 1.2 
               
               
                 P14635_C238 
                 — 
                 — 
                 — 
                 — 
                 — 
                 1.2 
               
               
                 Q8NDH3_C81 
                 — 
                 — 
                 — 
                 1.0 
                 — 
                 — 
               
               
                 Q9P0J1_C149 
                 — 
                 — 
                 — 
                 1.0 
                 — 
                 — 
               
               
                 Q96P48_C900 
                 — 
                 — 
                 1.1 
                 1.1 
                 — 
                 1.7 
               
               
                 Q96HE7_C37 
                 — 
                 — 
                 2.1 
                 0.6 
                 — 
                 — 
               
               
                 Q07065_C100 
                 — 
                 — 
                 — 
                 — 
                 — 
                 1.7 
               
               
                 Q9BRJ7_C88 
                 — 
                 — 
                 1.7 
                 — 
                 2.9 
                 — 
               
               
                 O75439_C265 
                 1.6 
                 0.6 
                 — 
                 1.0 
                 1.4 
                 — 
               
               
                 O43175_C369 
                 — 
                 — 
                 1.1 
                 20.0 
                 20.0 
                 — 
               
               
                 Q9UNI6_C265 
                 0.6 
                 0.8 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q06203_C100 
                 0.8 
                 — 
                 1.6 
                 0.6 
                 1.2 
                 — 
               
               
                 A0AVT1_C347 
                 0.8 
                 — 
                 — 
                 — 
                 1.9 
                 — 
               
               
                 Q86X76_C203 
                 — 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q6XZF7_C691 
                 — 
                 — 
                 — 
                 2.3 
                 — 
                 2.5 
               
               
                 Q15398_C129 
                 0.5 
                 — 
                 1.2 
                 — 
                 2.4 
                 1.3 
               
               
                 O75717_C773 
                 — 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q01433_C107 
                 0.4 
                 — 
                 — 
                 0.7 
                 — 
                 — 
               
               
                 Q8WV9_C464 
                 — 
                 — 
                 — 
                 — 
                 — 
                 2.2 
               
               
                 O14733_C131 
                 — 
                 — 
                 1.0 
                 — 
                 — 
                 — 
               
               
                 Q14137_C404 
                 0.6 
                 — 
                 1.5 
                 — 
                 — 
                 — 
               
               
                 Q96RU2_C171 
                 1.1 
                 1.1 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q9Y679_C391 
                 1.2 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 P51610_C1872 
                 — 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 P22307_C307 
                 — 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q9BTE3_C325 
                 — 
                 1.0 
                 — 
                 1.9 
                 3.5 
                 — 
               
               
                 Q9HA64_C24 
                 — 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q5TFE4_C119 
                 — 
                 — 
                 — 
                 3.1 
                 — 
                 — 
               
               
                 Q96N67_C2125 
                 0.9 
                 — 
                 — 
                 0.8 
                 — 
                 — 
               
               
                 P52948_C1312 
                 1.3 
                 — 
                 — 
                 — 
                 — 
                 1.8 
               
               
                 Q5UIP0_C2298 
                 — 
                 — 
                 — 
                 — 
                 — 
                 3.4 
               
               
                 P51812_C436 
                 — 
                 — 
                 1.3 
                 — 
                 — 
                 — 
               
               
                 Q92616_C1692 
                 0.5 
                 — 
                 — 
                 0.6 
                 2.0 
                 1.2 
               
               
                 Q15345_C297 
                 — 
                 — 
                 — 
                 0.9 
                 — 
                 1.9 
               
               
                 Q9NPH0_C267 
                 1.3 
                 — 
                 2.1 
                 — 
                 — 
                 — 
               
               
                 P04183_C66 
                 — 
                 — 
                 1.6 
                 0.7 
                 — 
                 — 
               
               
                 P42166_C629 
                 — 
                 — 
                 1.6 
                 — 
                 — 
                 — 
               
               
                 Q15013_C124 
                 1.0 
                 1.0 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q9Y5Y2_C72 
                 — 
                 — 
                 1.1 
                 — 
                 — 
                 — 
               
               
                 O15446_C86 
                 — 
                 — 
                 — 
                 — 
                 — 
                 1.6 
               
               
                 Q13630_C116 
                 — 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q8IYQ7_C324 
                 — 
                 — 
                 — 
                 — 
                 — 
                 1.4 
               
               
                 P05091_C319 
                 — 
                 — 
                 10.5 
                 — 
                 — 
                 — 
               
               
                 Q29RF7_C532 
                 — 
                 — 
                 — 
                 5.1 
                 8.1 
                 — 
               
               
                 Q9Y570_C381 
                 — 
                 — 
                 1.2 
                 — 
                 — 
                 — 
               
               
                 Q14980_C961 
                 2.4 
                 — 
                 — 
                 1.1 
                 — 
                 4.8 
               
               
                 P53384_C235 
                 — 
                 — 
                 — 
                 0.7 
                 — 
                 — 
               
               
                 Q15003_C418 
                 — 
                 — 
                 1.4 
                 — 
                 — 
                 — 
               
               
                 P53634_C258 
                 — 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q8NFF5_C499 
                 — 
                 — 
                 3.4 
                 — 
                 — 
                 — 
               
               
                 Q9ULA0_C144 
                 — 
                 — 
                 1.3 
                 — 
                 — 
                 — 
               
               
                 P22307_C94 
                 — 
                 20.0 
                 — 
                 — 
                 — 
                 — 
               
               
                 O15294_C620 
                 — 
                 — 
                 2.6 
                 1.1 
                 — 
                 — 
               
               
                 Q9Y5S2_C1517 
                 — 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q8TD19_C623 
                 — 
                 — 
                 — 
                 0.7 
                 1.4 
                 — 
               
               
                 Q8N2W9_C326 
                 — 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q13158_C98 
                 0.6 
                 — 
                 1.3 
                 0.9 
                 — 
                 — 
               
               
                 Q9UKX7_C151 
                 — 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q6PCB5_C280 
                 1.0 
                 — 
                 1.4 
                 — 
                 — 
                 — 
               
               
                 P10398_C597 
                 — 
                 — 
                 1.2 
                 — 
                 — 
                 — 
               
               
                 Q9UL40_C68 
                 1.9 
                 — 
                 2.4 
                 — 
                 — 
                 — 
               
               
                 P46013_C903 
                 — 
                 — 
                 1.6 
                 — 
                 — 
                 — 
               
               
                 Q16667_C39 
                 — 
                 — 
                 1.7 
                 — 
                 — 
                 — 
               
               
                 O75150_C890 
                 1.2 
                 — 
                 — 
                 0.7 
                 — 
                 — 
               
               
                 Q00610_C870 
                 — 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q9Y5T5_C205 
                 1.2 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 O95881_C66 
                 — 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q7Z5K2_C160 
                 — 
                 — 
                 0.7 
                 — 
                 — 
                 — 
               
               
                 P42166_C518 
                 — 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q9Y2S7_C143 
                 — 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 E2QRD5_C183 
                 — 
                 — 
                 — 
                 0.8 
                 — 
                 — 
               
               
                 O95833_C22 
                 — 
                 — 
                 — 
                 0.5 
                 — 
                 — 
               
               
                 O94953_C694 
                 — 
                 — 
                 1.1 
                 — 
                 — 
                 — 
               
               
                 O00541_C272 
                 — 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q9NXJ5_C149 
                 — 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q8N5L8_C131 
                 — 
                 — 
                   
                 — 
                 — 
                 1.7 
               
               
                 Q8IZ73_C246 
                 — 
                 — 
                 — 
                 0.4 
                 1.0 
                 — 
               
               
                 Q99798_C385 
                 — 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q9GZR2_C382 
                 — 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q13613_C117 
                 — 
                 — 
                 1.5 
                 — 
                 — 
                 — 
               
               
                 Q9NUI1_C22 
                 — 
                 — 
                 — 
                 0.7 
                 — 
                 — 
               
               
                 Q02556_C306 
                 — 
                 — 
                 1.4 
                 — 
                 2.0 
                 — 
               
               
                 Q9UPT9_C171 
                 — 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q8N999_C302 
                 — 
                 0.6 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q8IU81_C363 
                 — 
                 — 
                 — 
                 0.7 
                 — 
                 — 
               
               
                 Q9C0I1_C152 
                 — 
                 — 
                 4.6 
                 — 
                 — 
                 — 
               
               
                 Q9P2X3_C195 
                 — 
                 — 
                 — 
                 0.5 
                 — 
                 — 
               
               
                 Q6QNY0_C168 
                 — 
                 — 
                 1.6 
                 — 
                 — 
                 — 
               
               
                 Q15796_C81 
                 — 
                 — 
                 1.3 
                 — 
                 — 
                 — 
               
               
                 Q9NZB2_C531 
                 — 
                 — 
                 — 
                 — 
                 — 
                 2.4 
               
               
                 Q9HB90_C377 
                 — 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q9BR61_C267 
                 — 
                 — 
                 2.5 
                 — 
                 — 
                 — 
               
               
                 Pl6455_C145 
                 — 
                 — 
                 — 
                 — 
                 1.2 
                 — 
               
               
                 Q86UV5_C39 
                 — 
                 — 
                 — 
                 — 
                 1.3 
                 — 
               
               
                 A2A288_C367 
                 — 
                 — 
                 1.3 
                 — 
                 1.9 
                 — 
               
               
                 Q8NEC7_C140 
                 — 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q6PJG6_C673 
                 — 
                 — 
                 4.6 
                 — 
                 20.0 
                 — 
               
               
                 Q13232_C158 
                 — 
                 — 
                 1.5 
                 — 
                 — 
                 — 
               
               
                 Q86X76_C165 
                 — 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 P42695_C541 
                 — 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 P41226_C599 
                 — 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q99986_C50 
                 — 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q8WUM4_C90 
                 0.6 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 P29590_C213 
                 0.8 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q9P0K7_C973 
                 — 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 P53992_C78 
                 — 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q13867_C73 
                 — 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q8ND24_C655 
                 — 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q96EK4_C48 
                 — 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q96IV0_C309 
                 — 
                 — 
                 3.0 
                 — 
                 — 
                 — 
               
               
                 Q5T1V6_C414 
                 — 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q9UHQ1_C99 
                 — 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 O43396_C34 
                 — 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q8IV53_C174 
                 — 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                 Q8N9T8_C673 
                 — 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                   
               
            
           
           
               
               
               
               
               
               
               
            
               
                   
                   
                 38_200 μM —   
                 41_200 μM —   
                 45_200 μM —   
                 51_200 μM —   
                 56_200 μM —   
               
               
                   
                 Identifier 
                 insitu_231 
                 insitu_231 
                 insitu_231 
                 insitu_231 
                 insitu_231 
               
               
                   
                   
               
               
                   
                 P04406_C152 
                 0.9 
                 0.6 
                 20.0 
                 1.0 
                 0.9 
               
               
                   
                 P61978_C132 
                 1.0 
                 0.9 
                 9.3 
                 1.2 
                 0.8 
               
               
                   
                 Q13526_C113 
                 1.0 
                 0.6 
                 10.0 
                 1.4 
                 — 
               
               
                   
                 P24752_C119 
                 1.2 
                 1.9 
                 12.4 
                 0.7 
                 0.8 
               
               
                   
                 P24752_C413 
                 1.1 
                 0.9 
                 20.0 
                 1.1 
                 0.7 
               
               
                   
                 Q9NUY8_C283 
                 1.0 
                 0.7 
                 2.7 
                 2.1 
                 0.9 
               
               
                   
                 P13667_C206 
                 0.9 
                 1.0 
                 1.9 
                 5.3 
                 0.8 
               
               
                   
                 P12268_C140 
                 1.2 
                 0.7 
                 1.9 
                 1.0 
                 1.1 
               
               
                   
                 Q15365_C194 
                 2.5 
                 0.3 
                 1.5 
                 0.6 
                 1.2 
               
               
                   
                 Q9NVC6_C649 
                 1.2 
                 0.8 
                 20.0 
                 — 
                 0.8 
               
               
                   
                 P42166_C561 
                 20.0 
                 0.7 
                 20.0 
                 1.3 
                 1.1 
               
               
                   
                 Q9Y696_C35 
                 1.0 
                 0.6 
                 1.4 
                 2.6 
                 0.9 
               
               
                   
                 P10599_C32 
                 2.1 
                 0.4 
                 5.7 
                 13.9 
                 1.5 
               
               
                   
                 P31943_C267 
                 1.2 
                 1.0 
                 3.6 
                 1.3 
                 0.8 
               
               
                   
                 Q86SX6_C67 
                 1.0 
                 1.0 
                 9.1 
                 1.0 
                 0.8 
               
               
                   
                 P15121_C299 
                 1.0 
                 0.9 
                 1.0 
                 0.9 
                 0.9 
               
               
                   
                 P52597_C267 
                 1.8 
                 0.8 
                 4.1 
                 1.3 
                 0.9 
               
               
                   
                 Q9ULV4_C420 
                 1.4 
                 0.8 
                 3.2 
                 1.1 
                 1.0 
               
               
                   
                 P62888_C92 
                 3.2 
                 0.8 
                 2.2 
                 0.9 
                 0.9 
               
               
                   
                 Q9NQR4_C153 
                 1.1 
                 0.7 
                 2.0 
                 0.6 
                 0.8 
               
               
                   
                 P42765_C92 
                 0.9 
                 1.1 
                 15.1 
                 1.1 
                 — 
               
               
                   
                 Q15084_C55 
                 0.8 
                 0.9 
                 2.0 
                 5.0 
                 0.8 
               
               
                   
                 Q96HE7_C241 
                 1.6 
                 0.7 
                 2.1 
                 1.7 
                 0.9 
               
               
                   
                 Q99439_C164 
                 1.5 
                 0.4 
                 1.8 
                 — 
                 1.2 
               
               
                   
                 P25205_C119 
                 0.9 
                 0.9 
                 6.2 
                 2.6 
                 1.0 
               
               
                   
                 Q9NS86_C187 
                 2.0 
                 0.6 
                 3.1 
                 2.0 
                 1.2 
               
               
                   
                 Q15233_C145 
                 0.9 
                 1.1 
                 3.7 
                 1.6 
                 0.8 
               
               
                   
                 Q9BRA2_C43 
                 1.1 
                 0.6 
                 8.0 
                 — 
                 3.9 
               
               
                   
                 P35611_C68 
                 1.4 
                 0.9 
                 20.0 
                 1.0 
                 0.8 
               
               
                   
                 O75521_C380 
                 0.9 
                 1.1 
                 1.2 
                 1.0 
                 1.1 
               
               
                   
                 Q9BXW7_C392 
                 0.8 
                 1.0 
                 4.9 
                 1.1 
                 0.8 
               
               
                   
                 P30101_C406 
                 0.8 
                 1.0 
                 2.6 
                 6.0 
                 0.7 
               
               
                   
                 Q96AB3_C114 
                 1.2 
                 0.7 
                 3.1 
                 0.8 
                 — 
               
               
                   
                 P13667_C555 
                 0.8 
                 1.0 
                 2.6 
                 6.0 
                 0.7 
               
               
                   
                 Q09161_C44 
                 1.2 
                 0.8 
                 2.5 
                 1.2 
                 1.0 
               
               
                   
                 P78417_C32 
                 1.0 
                 0.3 
                 1.9 
                 — 
                 1.3 
               
               
                   
                 Q9ULW0_C536 
                 1.2 
                 1.2 
                 20.0 
                 1.4 
                 — 
               
               
                   
                 Q9NRG0_C55 
                 1.0 
                 0.9 
                 20.0 
                 1.1 
                 1.0 
               
               
                   
                 Q96T76_C848 
                 — 
                 0.7 
                 20.0 
                 — 
                 1.4 
               
               
                   
                 Q8TAQ2_C145 
                 1.3 
                 1.2 
                 2.9 
                 1.2 
                 0.8 
               
               
                   
                 Q9BVC5_C10 
                 0.9 
                 1.0 
                 3.4 
                 1.0 
                 0.8 
               
               
                   
                 Q7Z2W4_C645 
                 0.9 
                 0.9 
                 4.6 
                 1.6 
                 0.9 
               
               
                   
                 Q9BQ69_C186 
                 3.6 
                 1.2 
                 3.3 
                 1.2 
                 0.8 
               
               
                   
                 Q16831_C162 
                 1.4 
                 0.8 
                 1.3 
                 1.1 
                 1.1 
               
               
                   
                 P30101_C57 
                 0.9 
                 1.3 
                 2.6 
                 — 
                 0.7 
               
               
                   
                 P12268_C331 
                 1.3 
                 0.8 
                 4.1 
                 — 
                 — 
               
               
                   
                 O95571_C170 
                 — 
                 1.1 
                 3.1 
                 — 
                 0.8 
               
               
                   
                 O00299_C24 
                 1.0 
                 0.6 
                 — 
                 — 
                 0.9 
               
               
                   
                 O14879_C343 
                 — 
                 0.3 
                 4.0 
                 1.3 
                 1.2 
               
               
                   
                 Q96CM8_C64 
                 1.1 
                 0.8 
                 20.0 
                 — 
                 0.8 
               
               
                   
                 P51946_C244 
                 1.0 
                 1.2 
                 2.4 
                 0.7 
                 1.0 
               
               
                   
                 P49588_C773 
                 0.7 
                 0.7 
                 10.1 
                 — 
                 — 
               
               
                   
                 Q96RN5_C618 
                 1.4 
                 — 
                 20.0 
                 2.1 
                 0.8 
               
               
                   
                 O15294_C758 
                 — 
                 0.9 
                 2.9 
                 1.1 
                 1.0 
               
               
                   
                 P46734_C207 
                 1.5 
                 0.7 
                 1.5 
                 0.7 
                 1.3 
               
               
                   
                 Q96S55_C272 
                 1.3 
                 0.8 
                 2.5 
                 0.9 
                 0.9 
               
               
                   
                 O95229_C54 
                 — 
                 0.6 
                 — 
                 1.0 
                 1.0 
               
               
                   
                 O60610_C1227 
                 0.3 
                 0.6 
                 3.0 
                 — 
                 1.2 
               
               
                   
                 Q13428_C38 
                 1.1 
                 1.1 
                 2.8 
                 1.1 
                 0.8 
               
               
                   
                 Q9Y277_C65 
                 20.0 
                 1.4 
                 — 
                 — 
                 0.9 
               
               
                   
                 P57764_C268 
                 1.8 
                 0.6 
                 20.0 
                 1.8 
                 0.8 
               
               
                   
                 Q9Y3A3_C134 
                 1.0 
                 0.9 
                 2.3 
                 — 
                 0.9 
               
               
                   
                 Q02252_C317 
                 2.4 
                 0.8 
                 2.6 
                 — 
                 — 
               
               
                   
                 Q9NYL9_C132 
                 2.6 
                 0.3 
                 0.9 
                 0.8 
                 — 
               
               
                   
                 P83731_C6 
                 2.1 
                 0.3 
                 1.2 
                 — 
                 — 
               
               
                   
                 O95336_C32 
                 2.8 
                 0.6 
                 — 
                 — 
                 0.9 
               
               
                   
                 O13155_C291 
                 1.7 
                 0.7 
                 7.3 
                 1.1 
                 1.1 
               
               
                   
                 Q13418_C346 
                 1.0 
                 0.6 
                 — 
                 0.8 
                 — 
               
               
                   
                 A6NDU8_C179 
                 1.4 
                 0.6 
                 20.0 
                 — 
                 1.2 
               
               
                   
                 Q9UKF6_C498 
                 — 
                 1.0 
                 20.0 
                 — 
                 1.0 
               
               
                   
                 Q96F86_C413 
                 — 
                 — 
                 20.0 
                 20.0 
                 1.2 
               
               
                   
                 P42224_C492 
                 — 
                 0.6 
                 20.0 
                 2.4 
                 1.2 
               
               
                   
                 P11216_C326 
                 1.2 
                 0.7 
                 5.3 
                 0.8 
                 — 
               
               
                   
                 P21980_C277 
                 1.4 
                 0.6 
                 1.1 
                 1.0 
                 — 
               
               
                   
                 O9HAV7_C124 
                 1.0 
                 0.6 
                 2.1 
                 — 
                 0.7 
               
               
                   
                 P24752_C126 
                 — 
                 0.8 
                 — 
                 — 
                 0.8 
               
               
                   
                 Q9NQ88_C161 
                 — 
                 — 
                 20.0 
                 — 
                 1.4 
               
               
                   
                 Q13155_C23 
                 1.4 
                 — 
                 4.4 
                 1.2 
                 0.9 
               
               
                   
                 Q9NQW6_C712 
                 1.5 
                 0.7 
                 5.9 
                 — 
                 1.0 
               
               
                   
                 P51649_C340 
                 — 
                 — 
                 2.4 
                 — 
                 — 
               
               
                   
                 Q15021_C439 
                 1.1 
                 0.8 
                 — 
                 1.1 
                 1.2 
               
               
                   
                 Q5T0N5_C69 
                 1.5 
                 0.6 
                 5.4 
                 1.7 
                 1.0 
               
               
                   
                 P38606_C138 
                 2.1 
                 0.8 
                 — 
                 10.6 
                 1.1 
               
               
                   
                 Q9HCC0_C216 
                 — 
                 1.0 
                 7.0 
                 0.9 
                 0.7 
               
               
                   
                 Q9NQC3_C1101 
                 20.0 
                 1.0 
                 — 
                 1.2 
                 0.8 
               
               
                   
                 P35754_C23 
                 0.9 
                 0.5 
                 16.3 
                 — 
                 0.9 
               
               
                   
                 Q99757_C90 
                 3.6 
                 0.5 
                 6.7 
                 5.0 
                 — 
               
               
                   
                 Q9Y3D0_C93 
                 2.4 
                 0.6 
                 20.0 
                 20.0 
                 — 
               
               
                   
                 Q9UMS0_C213 
                 3.5 
                 0.9 
                 7.1 
                 1.8 
                 0.7 
               
               
                   
                 Q9NXV6_C516 
                 1.8 
                 0.9 
                 — 
                 — 
                 — 
               
               
                   
                 Q96RS6_C376 
                 1.3 
                 0.7 
                 — 
                 — 
                 — 
               
               
                   
                 Q14997_C1840 
                 20.0 
                 0.9 
                 — 
                 20.0 
                 — 
               
               
                   
                 P50570_C271 
                 0.9 
                 0.5 
                 15.4 
                 1.1 
                 — 
               
               
                   
                 Q86YH6_C71 
                 — 
                 0.9 
                 20.0 
                 — 
                 1.0 
               
               
                   
                 Q99497_C106 
                 1.1 
                 0.6 
                 20.0 
                 1.4 
                 — 
               
               
                   
                 Q9UJW0_C258 
                 — 
                 0.7 
                 2.7 
                 1.1 
                 1.3 
               
               
                   
                 Q9BUH6_C180 
                 1.4 
                 0.6 
                 5.5 
                 — 
                 1.3 
               
               
                   
                 P24752_C196 
                 1.0 
                 0.9 
                 — 
                 — 
                 0.8 
               
               
                   
                 Q13162_C51 
                 2.4 
                 — 
                 2.3 
                 — 
                 1.0 
               
               
                   
                 Q9BTA9_C553 
                 1.1 
                 1.0 
                 19.1 
                 1.2 
                 0.9 
               
               
                   
                 P48643_C253 
                 1.1 
                 0.8 
                 1.2 
                 0.8 
                 0.9 
               
               
                   
                 O75362_C286 
                 — 
                 1.0 
                 20.0 
                 — 
                 0.9 
               
               
                   
                 O60825_C158 
                 — 
                 0.7 
                 1.3 
                 0.9 
                 1.2 
               
               
                   
                 Q8NBS9_C350 
                 — 
                 0.9 
                 2.1 
                 — 
                 0.8 
               
               
                   
                 Q9NYL2_C22 
                 — 
                 0.6 
                 2.3 
                 — 
                 1.0 
               
               
                   
                 P277Q07_C9 
                 1.8 
                 0.4 
                 — 
                 — 
                 — 
               
               
                   
                 Q93009_C223 
                 0.8 
                 — 
                 20.0 
                 1.0 
                 — 
               
               
                   
                 O14929_C101 
                 1.1 
                 0.6 
                 20.0 
                 — 
                 — 
               
               
                   
                 Q9UPQ0_C140 
                 2.5 
                 0.5 
                 20.0 
                 — 
                 1.1 
               
               
                   
                 Q96NY7_C487 
                 — 
                 0.4 
                 1.8 
                 — 
                 1.3 
               
               
                   
                 Q9NQ88_C114 
                 — 
                 0.6 
                 4.6 
                 — 
                 — 
               
               
                   
                 Q14790_C360 
                 1.0 
                 0.5 
                 20.0 
                 — 
                 1.2 
               
               
                   
                 P04183_C230 
                 2.8 
                 0.6 
                 2.0 
                 0.7 
                 — 
               
               
                   
                 P68366_C54 
                 2.0 
                 — 
                 — 
                 — 
                 — 
               
               
                   
                 Q13428_C1298 
                 2.0 
                 1.0 
                 4.7 
                 — 
                 — 
               
               
                   
                 Q5MNZ6_C63 
                 — 
                 0.8 
                 2.6 
                 — 
                 0.7 
               
               
                   
                 O14980_C528 
                 2.1 
                 0.9 
                 — 
                 1.1 
                 — 
               
               
                   
                 Q86W42_C35 
                 0.8 
                 1.1 
                 20.0 
                 1.4 
                 0.7 
               
               
                   
                 Q9Y6G9_C51 
                 — 
                 0.7 
                 — 
                 — 
                 — 
               
               
                   
                 Q9NY27_C22 
                 1.0 
                 0.8 
                 20.0 
                 2.2 
                 — 
               
               
                   
                 Q8NFH5_C255 
                 1.1 
                 0.8 
                 5 5 
                 — 
                 — 
               
               
                   
                 Q9Y676_C128 
                 1.0 
                 — 
                 2.0 
                 1.0 
                 — 
               
               
                   
                 P35658_C728 
                 — 
                 1.1 
                 3.1 
                 — 
                 — 
               
               
                   
                 Q9NTX5_C133 
                 — 
                 — 
                 4.2 
                 — 
                 0.9 
               
               
                   
                 Q15118_C71 
                 1.3 
                 — 
                 20.0 
                 — 
                 — 
               
               
                   
                 Q00765_C18 
                 — 
                 — 
                 20.0 
                 — 
                 0.9 
               
               
                   
                 P22307_C71 
                 — 
                 1.2 
                 16.8 
                 5.6 
                 — 
               
               
                   
                 O75521_C312 
                 1.1 
                 — 
                 0.7 
                 — 
                 0.9 
               
               
                   
                 P49189_C288 
                 0.7 
                 0.8 
                 20.0 
                 — 
                 0.9 
               
               
                   
                 Q5T440_C170 
                 — 
                 0.7 
                 3.5 
                 — 
                 1.0 
               
               
                   
                 Q15084_C190 
                 1.0 
                 0.9 
                 2.8 
                 — 
                 — 
               
               
                   
                 Q96C19_C172 
                 0.7 
                 0.5 
                 — 
                 1.2 
                 — 
               
               
                   
                 P22061_C102 
                 — 
                 0.7 
                 — 
                 — 
                 — 
               
               
                   
                 Q9NP73_C86 
                 1.3 
                 0.5 
                 20.0 
                 1.3 
                 — 
               
               
                   
                 Q9BRF8_C54 
                 — 
                 0.7 
                 20.0 
                 — 
                 — 
               
               
                   
                 Q6ICB0_C108 
                 1.1 
                 — 
                 3.1 
                 1.1 
                 — 
               
               
                   
                 P29590_C389 
                 2.2 
                 0.4 
                 3.4 
                 0.9 
                 — 
               
               
                   
                 P07858_C211 
                 1.8 
                 0.4 
                 2.4 
                 — 
                 — 
               
               
                   
                 Q9NX18_C83 
                 — 
                 — 
                 3.7 
                 1.0 
                 0.7 
               
               
                   
                 P46109_C249 
                 1.6 
                 — 
                 20.0 
                 — 
                 0.8 
               
               
                   
                 P45984_C177 
                 — 
                 0.5 
                 — 
                 — 
                 1.1 
               
               
                   
                 P19447_C342 
                 1.0 
                 0.7 
                 5.9 
                 — 
                 0.7 
               
               
                   
                 P42166_C341 
                 — 
                 0.5 
                 — 
                 1.2 
                 — 
               
               
                   
                 Q8N1F7_C522 
                 1.7 
                 0.8 
                 20.0 
                 — 
                 — 
               
               
                   
                 Q86UY8_C276 
                 — 
                 1.7 
                 2.1 
                 1.2 
                 — 
               
               
                   
                 Q8WWI1_C228 
                 — 
                 0.8 
                 20.0 
                 — 
                 — 
               
               
                   
                 Q9NWA0_C139 
                 — 
                 0.8 
                 — 
                 — 
                 1.1 
               
               
                   
                 P09110_C381 
                 0.8 
                 0.9 
                 1.2 
                 — 
                 0.8 
               
               
                   
                 Q2NL82_C126 
                 0.9 
                 0.8 
                 20.0 
                 1.9 
                 — 
               
               
                   
                 Q5JPI3_C308 
                 — 
                 0.7 
                 — 
                 — 
                 0.7 
               
               
                   
                 P23919_C163 
                 5.7 
                 0.2 
                 — 
                 — 
                 0.9 
               
               
                   
                 Q96EB1_C218 
                 1.3 
                 — 
                 20.0 
                 — 
                 — 
               
               
                   
                 Q96FX7_C209 
                 1.0 
                 — 
                 20.0 
                 — 
                 0.9 
               
               
                   
                 O14933_C98 
                 1.6 
                 0.5 
                 20.0 
                 — 
                 — 
               
               
                   
                 Q29RF7_C242 
                 1.0 
                 — 
                 — 
                 1.8 
                 1.0 
               
               
                   
                 Q96T76_C819 
                 4.6 
                 0.6 
                 20.0 
                 — 
                 0.9 
               
               
                   
                 P23919_C117 
                 4.4 
                 — 
                 — 
                 — 
                 — 
               
               
                   
                 Q15149_C4574 
                 — 
                 0.9 
                 — 
                 — 
                 1.0 
               
               
                   
                 Q96RP9_C153 
                 — 
                 1.1 
                 — 
                 — 
                 — 
               
               
                   
                 P04818_C199 
                 20.0 
                 0.7 
                 20.0 
                 20.0 
                 — 
               
               
                   
                 P27708_C73 
                 — 
                 0.7 
                 — 
                 — 
                 — 
               
               
                   
                 P55265_C1224 
                 — 
                 — 
                 20.0 
                 1.3 
                 — 
               
               
                   
                 Q9Y3D2_C105 
                 1.6 
                 1.2 
                 20.0 
                 — 
                 — 
               
               
                   
                 O00244_C12 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                   
                 Q8WV74_C207 
                 — 
                 0.9 
                 20.0 
                 — 
                 — 
               
               
                   
                 Q9NRW3_C130 
                 — 
                 0.9 
                 20.0 
                 — 
                 0.9 
               
               
                   
                 P24468_C326 
                 — 
                 0.8 
                 20.0 
                 — 
                 — 
               
               
                   
                 P42166_C684 
                 3.0 
                 — 
                 6.8 
                 1.2 
                 1.1 
               
               
                   
                 Q96EY5_C231 
                 1.8 
                 — 
                 — 
                 — 
                 — 
               
               
                   
                 P14635_C238 
                 1.8 
                 0.5 
                 — 
                 — 
                 — 
               
               
                   
                 Q8NDH3_C81 
                 2.0 
                 — 
                 — 
                 — 
                 1.0 
               
               
                   
                 Q9P0J1_C149 
                 — 
                 0.9 
                 20.0 
                 — 
                 0.8 
               
               
                   
                 Q96P48_C900 
                 — 
                 0.5 
                 — 
                 — 
                 — 
               
               
                   
                 Q96HE7_C37 
                 3.4 
                 0.4 
                 20.0 
                 — 
                 — 
               
               
                   
                 Q07065_C100 
                 — 
                 1.0 
                 20.0 
                 — 
                 — 
               
               
                   
                 Q9BRJ7_C88 
                 — 
                 0.4 
                 — 
                 1.6 
                 1.0 
               
               
                   
                 O75439_C265 
                 — 
                 1.3 
                 — 
                 — 
                 — 
               
               
                   
                 O43175_C369 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                   
                 Q9UNI6_C265 
                 1.0 
                 1.0 
                 7.5 
                 — 
                 — 
               
               
                   
                 Q06203_C100 
                 1.2 
                 — 
                 — 
                 — 
                 — 
               
               
                   
                 A0AVT1_C347 
                 — 
                 0.6 
                 — 
                 — 
                 — 
               
               
                   
                 Q86X76_C203 
                 — 
                 1.3 
                 20.0 
                 — 
                 0.8 
               
               
                   
                 Q6XZF7_C691 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                   
                 Q15398_C129 
                 1.4 
                 — 
                 — 
                 7.4 
                 1.3 
               
               
                   
                 O75717_C773 
                 2.3 
                 1.0 
                 3.6 
                 — 
                 0.9 
               
               
                   
                 Q01433_C107 
                 — 
                 0.5 
                 — 
                 — 
                 — 
               
               
                   
                 Q8WVV9_C464 
                 1.5 
                 — 
                 20.0 
                 3.2 
                 — 
               
               
                   
                 O14733_C131 
                 20.0 
                 0.8 
                 — 
                 — 
                 — 
               
               
                   
                 Q14137_C404 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                   
                 Q96RU2_C171 
                 0.8 
                 — 
                 — 
                 — 
                 — 
               
               
                   
                 Q9Y679_C391 
                 — 
                 — 
                 20.0 
                 20.0 
                 0.7 
               
               
                   
                 P51610_C1872 
                 1.3 
                 0.5 
                 — 
                 — 
                 — 
               
               
                   
                 P22307_C307 
                 — 
                 1.1 
                 — 
                 — 
                 — 
               
               
                   
                 Q9BTE3_C325 
                 2.2 
                 0.6 
                 20.0 
                 — 
                 — 
               
               
                   
                 Q9HA64_C24 
                 1.7 
                 — 
                 — 
                 — 
                 1.0 
               
               
                   
                 Q5TFE4_C119 
                 — 
                 0.5 
                 — 
                 — 
                 — 
               
               
                   
                 Q96N67_C2125 
                 1.5 
                 0.7 
                 — 
                 — 
                 0.9 
               
               
                   
                 P52948_C1312 
                 1.3 
                 — 
                 — 
                 — 
                 — 
               
               
                   
                 Q5UIP0_C2298 
                 — 
                 1.2 
                 20.0 
                 — 
                 — 
               
               
                   
                 P51812_C436 
                 — 
                 4.5 
                 — 
                 — 
                 — 
               
               
                   
                 Q92616_C1692 
                 — 
                 0.7 
                 — 
                 — 
                 — 
               
               
                   
                 Q15345_C297 
                 1.4 
                 0.8 
                 — 
                 — 
                 — 
               
               
                   
                 Q9NPH0_C267 
                 — 
                 — 
                 20.0 
                 — 
                 — 
               
               
                   
                 P04183_C66 
                 — 
                 0.4 
                 — 
                 — 
                 — 
               
               
                   
                 P42166_C629 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                   
                 Q15013_C124 
                 — 
                 — 
                 20.0 
                 1.2 
                 — 
               
               
                   
                 Q9Y5Y2_C72 
                 1.7 
                 — 
                 — 
                 — 
                 — 
               
               
                   
                 O15446_C86 
                 — 
                 — 
                 4.6 
                 — 
                 — 
               
               
                   
                 Q13630_C116 
                 — 
                 — 
                 20.0 
                 — 
                 — 
               
               
                   
                 Q8IYQ7_C324 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                   
                 P05091_C319 
                 — 
                 0.9 
                 20.0 
                 — 
                 — 
               
               
                   
                 Q29RF7_C532 
                 — 
                 0.8 
                 — 
                 — 
                 — 
               
               
                   
                 Q9Y570_C381 
                 — 
                 0.2 
                 — 
                 — 
                 — 
               
               
                   
                 Q14980_C961 
                 2.6 
                 — 
                 — 
                 — 
                 — 
               
               
                   
                 P53384_C235 
                 2.0 
                 0.2 
                 — 
                 — 
                 — 
               
               
                   
                 Q15003_C418 
                 — 
                 — 
                 20.0 
                 — 
                 1.3 
               
               
                   
                 P53634_C258 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                   
                 Q8NFF5_C499 
                 — 
                 — 
                 — 
                 — 
                 1.3 
               
               
                   
                 Q9ULA0_C144 
                 — 
                 0.8 
                 — 
                 — 
                 0.9 
               
               
                   
                 P22307_C94 
                 — 
                 — 
                 20.0 
                 — 
                 — 
               
               
                   
                 O15294_C620 
                 — 
                 1.0 
                 — 
                 — 
                 — 
               
               
                   
                 Q9Y5S2_C1517 
                 — 
                 0.4 
                 20.0 
                 — 
                 — 
               
               
                   
                 Q8TD19_C623 
                 — 
                 0.6 
                 — 
                 — 
                 — 
               
               
                   
                 Q8N2W9_C326 
                 0.9 
                 0.8 
                 — 
                 — 
                 — 
               
               
                   
                 Q13158_C98 
                 1.5 
                 — 
                 — 
                 — 
                 — 
               
               
                   
                 Q9UKX7_C151 
                 — 
                 0.8 
                 — 
                 — 
                 — 
               
               
                   
                 Q6PCB5_C280 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                   
                 P10398_C597 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                   
                 Q9UL40_C68 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                   
                 P46013_C903 
                 1.1 
                 1.0 
                 20.0 
                 1.1 
                 — 
               
               
                   
                 Q16667_C39 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                   
                 O75150_C890 
                 — 
                 1.3 
                 — 
                 — 
                 — 
               
               
                   
                 Q00610_C870 
                 20.0 
                 — 
                 — 
                 — 
                 — 
               
               
                   
                 Q9Y5T5_C205 
                 1.5 
                 — 
                 — 
                 — 
                 — 
               
               
                   
                 O95881_C66 
                 1.0 
                 1.0 
                 — 
                 — 
                 — 
               
               
                   
                 Q7Z5K2_C160 
                 — 
                 1.0 
                 — 
                 — 
                 — 
               
               
                   
                 P42166_C518 
                 2.2 
                 — 
                 — 
                 — 
                 — 
               
               
                   
                 Q9Y2S7_C143 
                 — 
                 1.2 
                 — 
                 — 
                 0.8 
               
               
                   
                 E2QRD5_C183 
                 — 
                 0.5 
                 — 
                 — 
                 — 
               
               
                   
                 O95833_C22 
                 — 
                 — 
                 13.8 
                 — 
                 — 
               
               
                   
                 O94953_C694 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                   
                 O00541_C272 
                 — 
                 0.9 
                 — 
                 — 
                 — 
               
               
                   
                 Q9NXJ5_C149 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                   
                 Q8N5L8_C131 
                 — 
                 — 
                 7.3 
                 — 
                 — 
               
               
                   
                 Q8IZ73_C246 
                 1.7 
                 — 
                 — 
                 — 
                 — 
               
               
                   
                 Q99798_C385 
                 — 
                 0.1 
                 — 
                 — 
                 — 
               
               
                   
                 Q9GZR2_C382 
                 — 
                 — 
                 20.0 
                 — 
                 — 
               
               
                   
                 Q13613_C117 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                   
                 Q9NUI1_C22 
                 — 
                 — 
                 17.0 
                 — 
                 — 
               
               
                   
                 Q02556_C306 
                 — 
                   
                 — 
                 — 
                 — 
               
               
                   
                 Q9UPT9_C171 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                   
                 Q8N999_C302 
                 — 
                 0.3 
                 20.0 
                 — 
                 — 
               
               
                   
                 Q8IU81_C363 
                 1.3 
                 — 
                 1.7 
                 — 
                 — 
               
               
                   
                 Q9C0I1_C152 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                   
                 Q9P2X3_C195 
                 — 
                 — 
                 20.0 
                 — 
                 — 
               
               
                   
                 Q6QNY0_C168 
                 1.0 
                 — 
                 — 
                 — 
                 — 
               
               
                   
                 Q15796_C81 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                   
                 Q9NZB2_C531 
                 — 
                 — 
                 — 
                 — 
                 0.6 
               
               
                   
                 Q9HB90_C377 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                   
                 Q9BR61_C267 
                 — 
                 0.5 
                 — 
                 — 
                 — 
               
               
                   
                 Pl6455_C145 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                   
                 Q86UV5_C39 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                   
                 A2A288_C367 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                   
                 Q8NEC7_C140 
                 — 
                 — 
                 20.0 
                 — 
                 — 
               
               
                   
                 Q6PJG6_C673 
                 — 
                 — 
                 — 
                 — 
                 0.9 
               
               
                   
                 Q13232_C158 
                 — 
                 — 
                 8.8 
                 — 
                 — 
               
               
                   
                 Q86X76_C165 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                   
                 P42695_C541 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                   
                 P41226_C599 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                   
                 Q99986_C50 
                 — 
                 — 
                 4.1 
                 — 
                 — 
               
               
                   
                 Q8WUM4_C90 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                   
                 P29590_C213 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                   
                 Q9P0K7_C973 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                   
                 P53992_C78 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                   
                 Q13867_C73 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                   
                 Q8ND24_C655 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                   
                 Q96EK4_C48 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                   
                 Q96IV0_C309 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                   
                 Q5T1V6_C414 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                   
                 Q9UHQ1_C99 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                   
                 O43396_C34 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                   
                 Q8IV53_C174 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                   
                 Q8N9T8_C673 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                   
                   
               
            
           
         
       
     
     Table 3 illustrates a list of cysteine containing proteins and potential cysteine site of conjugation. 
     
       
         
           
               
               
               
               
             
               
                   
               
               
                   
                   
                 Cysteine 
                   
               
               
                 Identifier 
                 Protein Name 
                 Location 
                 Protein Class 
               
               
                   
               
             
            
               
                 O00170 
                 AIP AH receptor-interacting protein 
                 C122 
                 Uncategorized 
               
               
                 O00541 
                 PES1 Pescadillo homolog 
                 C272; C361 
                 Uncategorized 
               
               
                 O00622 
                 CYR61 Protein CYR61 
                 C39; C70; C134 
                 Uncategorized 
               
               
                 O14920 
                 IKBKB Inhibitor of nuclear factor kappa-B 
                 C464 
                 Enzyme 
               
               
                   
                 kinase subunit 
                   
                   
               
               
                 O14933 
                 UBE2L6 Ubiquitin/ISG15-conjugating enzyme 
                 C98 
                 Enzyme 
               
               
                   
                 E2 L6 PCTK 
                   
                   
               
               
                 O14980 
                 XPO1 Exportin-1 
                 C34; C528; 
                 Uncategorized 
               
               
                   
                   
                 C1070 
                   
               
               
                 O75362 
                 ZNF217 Zinc finger protein 217 
                 C286 
                 Transcription 
               
               
                   
                   
                   
                 factors and 
               
               
                   
                   
                   
                 regulators 
               
               
                 O94953 
                 KDM4B Lysine-specific demethylase 4B 
                 C694 
                 Enzyme 
               
               
                 P00813 
                 ADA Adenosine deaminase 
                 C75 
                 Enzyme 
               
               
                 P04150 
                 NR3C1 Glucocorticoid receptor 
                 C302; C622 
                 Transcription 
               
               
                   
                   
                   
                 factors and 
               
               
                   
                   
                   
                 regulators 
               
               
                 P09086 
                 POU2F2 POU domain, class 2, transcription 
                 C346 
                 Transcription 
               
               
                   
                 factor 2 
                   
                 factors and 
               
               
                   
                   
                   
                 regulators 
               
               
                 P09211 
                 GSTP1 Glutathione S-transferase P 
                 C48 
                 Enzyme 
               
               
                 P14598 
                 NCF1 Neutrophil cytosol factor 1 
                 C378 
                 Adapter, 
               
               
                   
                   
                   
                 scaffolding, 
               
               
                   
                   
                   
                 modulator 
               
               
                   
                   
                   
                 proteins 
               
               
                 P15374 
                 UCHL3 Ubiquitin carboxyl-terminal hydrolase 
                 C95 
                 Enzyme 
               
               
                   
                 isozyme L3 
                   
                   
               
               
                 P16455 
                 MGMT Methylated-DNA--protein-cysteine 
                 C145; C150 
                 Enzyme 
               
               
                   
                 methyltransferase 
                   
                   
               
               
                 P17812 
                 CTP synthase 1 
                 C491 
                 Enzyme 
               
               
                 P19447 
                 ERCC3 TFIIH basal transcription factor 
                 C342 
                 Enzyme 
               
               
                   
                 complex helicase 
                   
                   
               
               
                 P21580 
                 TNFAIP3 Tumor necrosis factor alpha-induced 
                 C54 
                 Enzyme 
               
               
                   
                 protein 3 
                   
                   
               
               
                 P24752 
                 ACAT1 Acetyl-CoA acetyltransferase, 
                 C119; C126; 
                 Enzyme 
               
               
                   
                 mitochondrial 
                 C196; C413 
                   
               
               
                 P40261 
                 Nicotinamide N-methyltransferase 
                 C165 
                 Enzyme 
               
               
                 P40763 
                 STAT3 Signal transducer and activator of 
                 C259 
                 Transcription 
               
               
                   
                 transcription 3 
                   
                 factors and 
               
               
                   
                   
                   
                 regulators 
               
               
                 P41226 
                 UBA7 Ubiquitin-like modifier-activating 
                 C599 
                 Enzyme 
               
               
                   
                 enzyme 7 
                   
                   
               
               
                 P42575 
                 CASP2 Caspase-2 
                 C370 
                 Enzyme 
               
               
                 P43403 
                 ZAP70 Tyrosine-protein kinase ZAP-70 
                 C117 
                 Enzyme 
               
               
                 P48200 
                 IREB2 Iron-responsive element-binding 
                 C137 
                 Transcription 
               
               
                   
                 protein 2 
                   
                 factors and 
               
               
                   
                   
                   
                 regulators 
               
               
                 P48735 
                 IDH2 Isocitrate dehydrogenase 
                 C308 
                 Enzyme 
               
               
                 P50851 
                 LRBA Lipopolysaccharide-responsive and 
                 C1704; C2675 
                 Uncategorized 
               
               
                   
                 beige-like anchor protein 
                   
                   
               
               
                 P51617 
                 IRAK1 Interleukin-1 receptor-associated 
                 C608 
                 Enzyme 
               
               
                   
                 kinase 1 
                   
                   
               
               
                 P61081 
                 NEDD8-conjugating enzyme Ubc12 
                 C47 
                 Enzyme 
               
               
                 P61088 
                 Ubiquitin-conjugating enzyme E2 N 
                 C87 
                 Enzyme 
               
               
                 P63244 
                 GNB2L1 Guanine nucleotide-binding protein 
                 C182 
                 Channels, 
               
               
                   
                 subunit beta-2-like 1 
                   
                 Transporters, 
               
               
                   
                   
                   
                 Receptors 
               
               
                 P68036 
                 UBE2L3 Ubiquitin-conjugating enzyme E2 L3 
                 C86 
                 Enzyme 
               
               
                 Q00535 
                 CDK5 Cyclin-dependent kinase 5 
                 C157 
                 Enzyme 
               
               
                 Q01201 
                 RELB Transcription factor RelB 
                 C109 
                 Transcription 
               
               
                   
                   
                   
                 factors and 
               
               
                   
                   
                   
                 regulators 
               
               
                 Q02556 
                 IRF8 Interferon regulatory factor 8 
                 C306 
                 Transcription 
               
               
                   
                   
                   
                 factors and 
               
               
                   
                   
                   
                 regulators 
               
               
                 Q04759 
                 PRKCQ Protein kinase C theta type 
                 C14; C17 
                 Enzyme 
               
               
                 Q06124 
                 Tyrosine-protein phosphatase non-receptor 
                 C573 
                 Enzyme 
               
               
                   
                 type 11 
                   
                   
               
               
                 Q09472 
                 EP300 Histone acetyltransferase p300 
                 C1738 
                 Enzyme 
               
               
                 Q14790 
                 CASP8 Caspase-8 
                 C360 
                 Enzyme 
               
               
                 Q15084 
                 PDIA6 Protein disulfide-isomerase A6 
                 C55; C58; C190; 
                 Enzyme 
               
               
                   
                   
                 C193 
                   
               
               
                 Q15306 
                 IRF4 Interferon regulatory factor 4 
                 C194 
                 Transcription 
               
               
                   
                   
                   
                 factors and 
               
               
                   
                   
                   
                 regulators 
               
               
                 Q15910 
                 EZH2 Histone-lysine N-methyltransferase 
                 C503 
                 Enzyme 
               
               
                   
                 EZH2 
                   
                   
               
               
                 Q16186 
                 Proteasomal ubiquitin receptor ADRM1 
                 C88 
                 Channels, 
               
               
                   
                   
                   
                 Transporters, 
               
               
                   
                   
                   
                 Receptors 
               
               
                 Q16763 
                 UBE2S Ubiquitin-conjugating enzyme E2 S 
                 C118 
                 Enzyme 
               
               
                 Q16822 
                 PCK2 Phosphoenolpyruvate carboxykinase 
                 C306 
                 Enzyme 
               
               
                 Q16875 
                 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 
                 C155 
                 Enzyme 
               
               
                   
                 3 
                   
                   
               
               
                 Q16877 
                 PFKFB4 6-phosphofructo-2-kinase/fructose- 
                 C159 
                 Enzyme 
               
               
                   
                 2,6-bisphosphata 
                   
                   
               
               
                 Q6L8Q7 
                 PDE12 2,5-phosphodiesterase 12 
                 C108 
                 Enzyme 
               
               
                 Q70CQ2 
                 USP34 Ubiquitin carboxyl-terminal hydrolase 
                 C741; C1090 
                 Enzyme 
               
               
                   
                 34 
                   
                   
               
               
                 Q7Z2W4 
                 ZC3HAV1 Zinc finger CCCH-type antiviral 
                 C645 
                 Transcription 
               
               
                   
                 protein 1 
                   
                 factors and 
               
               
                   
                   
                   
                 regulators 
               
               
                 Q86UV5 
                 USP48 Ubiquitin carboxyl-terminal hydrolase 
                 C39 
                 Enzyme 
               
               
                   
                 48 
                   
                   
               
               
                 Q8TAQ2 
                 SMARCC2 SWI/SNF complex subunit 
                 C145 
                 Transcription 
               
               
                   
                 SMARCC2 
                   
                 factors and 
               
               
                   
                   
                   
                 regulators 
               
               
                 Q92851 
                 Caspase-10 
                 C401 
                 Enzyme 
               
               
                 Q93009 
                 USP7 Ubiquitin carboxyl-terminal hydrolase 7 
                 C223; C315 
                 Enzyme 
               
               
                 Q96FA3 
                 PELI1 E3 ubiquitin-protein ligase pellino 
                 C282 
                 Enzyme 
               
               
                   
                 homolog 1 
                   
                   
               
               
                 Q96GG9 
                 DCUN1D1 DCN1-like protein 1 
                 C115 
                 Uncategorized 
               
               
                 Q96JH7 
                 VCPIP1 Deubiquitinating protein VCIP135 
                 C219 
                 Enzyme 
               
               
                 Q96RU2 
                 USP28 Ubiquitin carboxyl-terminal hydrolase 
                 C171; C733 
                 Enzyme 
               
               
                   
                 28 
                   
                   
               
               
                 Q99873 
                 PRMT1 Protein arginine N-methyltransferase 
                 C109 
                 Enzyme 
               
               
                   
                 1 
                   
                   
               
               
                 Q9C0C9 
                 UBE2O Ubiquitin-conjugating enzyme E2 O 
                 C375 
                 Enzyme 
               
               
                 Q9HB90 
                 RRAGC Ras-related GTP-binding protein C 
                 C358; C377 
                 Channels, 
               
               
                   
                   
                   
                 transporters, and 
               
               
                   
                   
                   
                 receptors 
               
               
                 Q9NRW4 
                 Dual specificity protein phosphatase 22 
                 C124 
                 Enzyme 
               
               
                 Q9NWZ3 
                 IRAK4 Interleukin-1 receptor-associated 
                 C13 
                 Enzyme 
               
               
                   
                 kinase 4 
                   
                   
               
               
                 Q9NYL2 
                 MLTK Mitogen-activated protein kinase 
                 C22 
                 Enzyme 
               
               
                   
                 kinase kinase MLT 
                   
                   
               
               
                 Q9UPT9 
                 USP22 Ubiquitin carboxyl-terminal hydrolase 
                 C44; C171 
                 Enzyme 
               
               
                   
                 22 
                   
                   
               
               
                 Q9Y3Z3 
                 SAMHD1 SAM domain and HD domain-containing 
                 C522 
                 Enzyme 
               
               
                   
                 protein 1 
                   
                   
               
               
                 Q9Y4C1 
                 KDM3A Lysine-specific demethylase 3A 
                 C251 
                 Enzyme 
               
               
                 Q9Y5T5 
                 USP16 Ubiquitin carboxyl-terminal hydrolase 
                 C205 
                 Enzyme 
               
               
                   
                 16 
               
               
                   
               
            
           
         
       
     
     Table 4 shows representative cysteines with known covalent ligands targeted by fragment electrophiles in isoTOP-ABPP experiments. 
     
       
         
           
               
               
               
               
               
               
             
               
                   
               
               
                   
                   
                   
                 Other cysteines 
                 Previous 
                   
               
               
                   
                 Liganded 
                   
                 quantified by 
                 covalent 
                 Cysteine 
               
               
                 Protein 
                 cysteine 
                 Fragment(s) 
                 isoTOP-ABPP 
                 inhibitor(s) 
                 location 
               
               
                   
               
             
            
               
                 BTK 
                 C481 
                 2, 3, 14, 31 
                 C145, C337 
                 Ibrutinib 
                 Active site 
               
               
                 TGM2 
                 C277 
                 12, 14, 32 
                 C10, C27, C230, 
                 18d 
                 Active Site 
               
               
                   
                   
                   
                 C269, C290, C336, 
                   
                   
               
               
                   
                   
                   
                 C370, C524, C545, 
                   
                   
               
               
                   
                   
                   
                 C620 
                   
                   
               
               
                 Map2k7 
                 C131 
                 2, 3, 11, 14, 20, 
                 C260, C280 
                 Ibrutinib 
                 Active Site 
               
               
                   
                   
                 21, 38 
                   
                   
                   
               
               
                 XPO1 
                 C528 
                 2, 3, 5, 14, 24, 
                 C34, C119, C164, 
                 KPT-330 
                 Non-active 
               
               
                   
                   
                 31, 43, 56 
                 C199, C327, C498, 
                   
                 site 
               
               
                   
                   
                   
                 C723, C1070 
                   
                   
               
               
                 Casp5 
                 C315 
                 3, 50 
                 — 
                 Z-WEHD-CHO/FMK 
                 Active Site 
               
               
                   
                   
                   
                   
                 (“WEHD” disclosed as 
                   
               
               
                   
                   
                   
                   
                 SEQ ID NO: 863) 
                   
               
               
                 Casp8 
                 C360 
                 2, 4, 11 
                 C236, C409 
                 Z-VAD-FMK, 
                 Active Site 
               
               
                   
                   
                   
                   
                 CV8/9-AOMK 
                   
               
               
                 ERCC3 
                 C342 
                 2, 3, 5, 8, 14, 21 
                 — 
                 Triptolide 
                 Active Site 
               
               
                 Park 7 
                 C106 
                 2, 9, 8, 11, 13, 
                 , C46, C53 
                 WRR-086 
                 Active Site 
               
               
                 (Toxoplasma 
                   
                 43, 45, 50, 52 
                   
                   
                   
               
               
                 DJ-1) 
                   
                   
                   
                   
                   
               
               
                 GSTO1 
                 C32 
                 2-13, 16, 18-22, 
                 C90, C192, C237 
                 KT53 
                 Active Site 
               
               
                   
                   
                 33, 27-30, 32-34, 
                   
                   
                   
               
               
                   
                   
                 36, 39, 43, 
                   
                   
                   
               
               
                   
                   
                 49, 50, 52, 54, 
                   
                   
                   
               
               
                   
                   
                 55 
                   
                   
                   
               
               
                 ALDH2 
                 C319 
                 3, 8-10, 12, 27, 
                 C66, C179, C386, 
                 Disulfiram 
                 Active Site 
               
               
                   
                   
                 28, 32, 39, 40, 
                 C472 
                   
                   
               
               
                   
                   
                 43, 49, 50 
                   
                   
                   
               
               
                 CTSZ 
                 C92 
                 4, 11, 20, 28, 32 
                 C89, C126, C132, 
                 Cy5DCG04 
                 Active Site 
               
               
                   
                   
                   
                 C154, C170, C173, 
                   
                   
               
               
                   
                   
                   
                 C179, C214 
               
               
                   
               
            
           
         
       
     
     Table 5 shows Reactive docking results for liganded cysteines. 
     
       
         
           
               
               
               
               
               
               
             
               
                   
               
               
                   
                   
                 Most ligandable 
                   
                 Most ligandable 
                   
               
               
                   
                   
                 cysteine by 
                 Cysteine 
                 cysteine by 
                   
               
               
                 Protein 
                 PDB ID: 
                 docking 
                 location 
                 isoTOP-ABPP 
                 Match 
               
               
                   
               
             
            
               
                 Aldh2 
                 1O05 
                 C319 
                 Active site 
                 C319 
                 Yes 
               
               
                 BTK 
                 1K2P 
                 C481 
                 Active site 
                 C481 
                 Yes 
               
               
                 CASP8 
                 1QTN 
                 C360 
                 Active Site 
                 C360 
                 Yes 
               
               
                 CCNB1 
                 2JGZ 
                 C238 
                 Non-active site 
                 C238 
                 Yes 
               
               
                 CDKN3 
                 1FQ1 
                 C39 
                 Non-active site 
                 C39 
                 Yes 
               
               
                 CLIC4 
                 2AEH 
                 C35 
                 Non-active site 
                 C35 
                 Yes 
               
               
                 DTYMK 
                 1E2G 
                 C163 
                 Non-active site 
                 C163 
                 Yes 
               
               
                 IDH1 
                 3MAP 
                 C269 
                 Non-active site 
                 C269 
                 Yes 
               
               
                 IMPDH2 
                 1NF7 
                 C331 
                 Active site 
                 C331, C140 
                 Yes 
               
               
                 GLRX5 
                 2WUL 
                 C67 
                 Active site 
                 C67 
                 Yes 
               
               
                 GSTO1 
                 1EEM 
                 C32 
                 Active site 
                 C32 
                 Yes 
               
               
                 NME3 
                 1ZS6 
                 C158 
                 Non-active site 
                 C158 
                 Yes 
               
               
                 PKM 
                 4JPG 
                 C423 
                 Non-active site 
                 C423 
                 Yes 
               
               
                 SRC 
                 2SRC 
                 C277 
                 Active Site 
                 C277 
                 Yes 
               
               
                 TIGAR 
                 3DCY 
                 C114 
                 Non-active site 
                 C114, C161 
                 Yes 
               
               
                 TXNDC 
                 1WOU 
                 C43 
                 Active site 
                 C43 
                 Yes 
               
               
                 UGDH 
                 3ITK 
                 C276 
                 Active site 
                 C276 
                 Yes 
               
               
                 UPP1 
                 3EUF 
                 C162 
                 Non-active site 
                 C162 
                 Yes 
               
               
                 XPO1 
                 3GB8 
                 C528 
                 Non-active site 
                 C528 
                 Yes 
               
               
                 CDK5 
                 1UNG 
                 C157 
                 Non-active site 
                 C269 
                 Second 
               
               
                 EDC3 
                 3D3K 
                 C311 
                 Non-active site 
                 C137, C413, C499 
                 Second 
               
               
                 NR2F2 
                 3CJW 
                 C213 
                 Non-active site 
                 C326, C213 (in situ) 
                 Second 
               
               
                 PDCD6IP 
                 2R02 
                 C231 
                 Non-active site 
                 C90 
                 Second 
               
               
                 PRMT1 
                 1ORI 
                 C285 
                 Active site 
                 C109 
                 Second 
               
               
                 UBE2S 
                 1ZDN 
                 C118 
                 Non-active site 
                 C95 
                 Second 
               
               
                 FNBP1 
                 2EFL 
                 C145 
                 Non-active site 
                 C70 
                 No 
               
               
                 HAT1 
                 2P0W 
                 C120 
                 Non-active site 
                 C101 
                 No 
               
               
                 MAPK9 
                 3NPC 
                 C163 
                 Active site 
                 C177 
                 No 
               
               
                 STAT1 
                 1YVL 
                 C543 
                 Non-active site 
                 C492, C255 
                 No 
               
               
                   
               
            
           
         
       
     
     Table 6 shows site of fragment labeling for recombinant proteins. The underlines portion indicates the fragment-modified cysteines. 
     
       
         
           
               
               
               
               
               
               
               
               
             
               
                   
               
               
                   
                   
                   
                   
                   
                 M + H 
                 M + H 
                   
               
               
                   
                   
                   
                   
                 SEQ 
                 calculated 
                 observed 
                   
               
               
                 Protein 
                 Cysteine 
                 Fragment # 
                 Peptide 
                 ID NO: 
                 (m/z) 
                 (m/z) 
                 Charge 
               
               
                   
               
             
            
               
                 IMPDH2 
                 C140 
                 14 
                 R.HGF C GIPITDTGR.M 
                  45 
                  715.86 
                  715.86 
                 2 
               
               
                   
               
               
                 TIGAR 
                 C114 
                  5 
                 R.EE C PVFTPPGGETLDQVK.M 
                 143 
                 1123.97 
                 1123.97 
                 2 
               
               
                   
               
               
                 CASP8 
                 C360 
                  7 
                 K.VFFIQA C QGDNYQK.G 
                 335 
                  660.98 
                  660.98 
                 3 
               
               
                   
               
               
                 IDH1 
                 C269 
                 20 
                 K.SEGGFIWA C K.N 
                 260 
                  702.84 
                  702.84 
                 2 
               
               
                   
               
            
           
         
       
     
     Table 7 illustrates a list of DMF-sensitive Cys residues in human T cells, defined as Cys residues that showed R values (DMSO/DMF)&gt;4 in isoTOP-ABPP experiments comparing DMSO-versus DMF-treated T cells. 
     
       
         
           
               
               
               
               
               
               
             
               
                   
               
               
                   
                   
                   
                   
                 Conserved 
                 Role in 
               
               
                 Name 
                 Full name 
                 Protein function 
                 Residue 
                 in mice 
                 immunology 
               
               
                   
               
             
            
               
                 ADA 
                 Adenosine 
                 Adenosine 
                 C75 
                 yes 
                 Positive regulator 
               
               
                   
                 deaminase 
                 deaminase 
                   
                   
                 of T cell co-activation 
               
               
                 AGFG2 
                 Arf-GAP domain 
                 GTPase activator 
                 C39 
                 yes 
                 Unknown 
               
               
                   
                 and FG repeat- 
                   
                   
                   
                   
               
               
                   
                 containing protein 2 
                   
                   
                   
                   
               
               
                 AIP 
                 AH receptor- 
                 Transcription factor 
                 C122 
                 yes 
                 Unknown 
               
               
                   
                 interacting protein 
                 binding 
                   
                   
                   
               
               
                 CRKL 
                 Crk-like protein 
                 Poly(A) RNA 
                 C249 
                 yes 
                 Unknown 
               
               
                   
                   
                 binding 
                   
                   
                   
               
               
                 FLII 
                 Protein flightless-1 
                 Actin binding 
                 C46 
                 yes 
                 Unknown 
               
               
                   
                 homolog 
                   
                   
                   
                   
               
               
                 GAK 
                 Cyclin-G-associated 
                 Serine/threonine 
                 C87 
                 yes 
                 Unknown 
               
               
                   
                 kinase 
                 protein kinase 
                   
                   
                   
               
               
                 HUWE1 
                 E3 ubiquitin-protein 
                 E3 ubiquitin- 
                 C3372 
                 yes 
                 Unknown 
               
               
                   
                 ligase HUWE1 
                 protein ligase 
                   
                   
                   
               
               
                 IKBKB 
                 Inhibitor of nuclear 
                 Serine kinase 
                 C464 
                 yes 
                 Phosphorylates 
               
               
                   
                 factor kappa-B 
                   
                   
                   
                 IkB-α in NF-κB 
               
               
                   
                 kinase subunit 
                   
                   
                   
                 pathway 
               
               
                 1L16 
                 Pro-interleukin-16 
                 Cytokine 
                 C1004 
                 yes 
                 Influences 
               
               
                   
                   
                   
                   
                   
                 migration of 
               
               
                   
                   
                   
                   
                   
                 CD4+ 
               
               
                   
                   
                   
                   
                   
                 lymphocytes 
               
               
                 IRF4 
                 Interferon 
                 DNA binding 
                 C194 
                 yes 
                 Regulates 
               
               
                   
                 regulatory factor 4 
                   
                   
                   
                 dendritic cell and 
               
               
                   
                   
                   
                   
                   
                 B cell 
               
               
                   
                   
                   
                   
                   
                 development, as 
               
               
                   
                   
                   
                   
                   
                 well as T/B cell 
               
               
                   
                   
                   
                   
                   
                 differentiation 
               
               
                 IRF8 
                 Interferon 
                 DNA binding 
                 C306 
                 yes 
                 Plays a negative 
               
               
                   
                 regulatory factor 8 
                   
                   
                   
                 regulatory role in 
               
               
                   
                   
                   
                   
                   
                 immune cells. 
               
               
                   
                   
                   
                   
                   
                 Binds to upstream 
               
               
                   
                   
                   
                   
                   
                 regulatory region 
               
               
                   
                   
                   
                   
                   
                 of MHC class I 
               
               
                   
                   
                   
                   
                   
                 genes. Regulates 
               
               
                   
                   
                   
                   
                   
                 the development 
               
               
                   
                   
                   
                   
                   
                 and differentiation 
               
               
                   
                   
                   
                   
                   
                 of myeloid cells. 
               
               
                 KIAA0528 
                 Uncharacterized 
                 Calcium-dependent 
                 C993 
                 yes 
                 Unknown 
               
               
                   
                 protein 
                 phospholipid 
                   
                   
                   
               
               
                   
                   
                 binding 
                   
                   
                   
               
               
                 LAS1L 
                 Ribosomal 
                 Poly(A) RNA 
                 C456 
                 yes 
                 Unknown 
               
               
                   
                 biogenesis protein 
                 binding 
                   
                   
                   
               
               
                 MARS2 
                 Methionine--tRNA 
                 Methionine-tRNA 
                 C425 
                 yes 
                 Unknown 
               
               
                   
                 ligase, 
                 ligase 
                   
                   
                   
               
               
                   
                 mitochondrial 
                   
                   
                   
                   
               
               
                 MAT2A 
                 S-adenosylmethionine 
                 Methionine 
                 C56 
                 yes 
                 Unknown 
               
               
                   
                 synthase isoform 
                 adenosyltransferase 
                   
                   
                   
               
               
                   
                 type-2 
                   
                   
                   
                   
               
               
                 MAT2A 
                 S-adenosylmethionine 
                 Methionine 
                 C104 
                 yes 
                 Unknown 
               
               
                   
                 synthase isoform 
                 adenosyltransferase 
                   
                   
                   
               
               
                   
                 type-2 
                   
                   
                   
                   
               
               
                 MTCH2 
                 Mitochondrial 
                 Induces 
                 C296 
                 yes 
                 Unknown 
               
               
                   
                 carrier homolog 2 
                 mitochondrial 
                   
                   
                   
               
               
                   
                   
                 depolarization 
                   
                   
                   
               
               
                 PGP 
                 Phosphoglycolate 
                 Phosphatase 
                 C297 
                 yes 
                 Unknown 
               
               
                   
                 phosphatase 
                   
                   
                   
                   
               
               
                 PML 
                 Protein 
                 RNA/DNA binding 
                 C479 
                 yes 
                 Modulates TGF- 
               
               
                   
                 Promyelocytic 
                   
                   
                   
                 beta signaling, 
               
               
                   
                 leukemia 
                   
                   
                   
                 induced by 
               
               
                   
                   
                   
                   
                   
                 interferon to 
               
               
                   
                   
                   
                   
                   
                 promote antiviral 
               
               
                   
                   
                   
                   
                   
                 responses 
               
               
                 PRKCQ 
                 Protein kinase C 
                 Serine/threonine 
                 C14 
                 yes 
                 Promotes TCR 
               
               
                   
                 theta type 
                 protein kinase 
                   
                   
                 signaling through 
               
               
                   
                   
                   
                   
                   
                 activation of NF- 
               
               
                   
                   
                   
                   
                   
                 κB and other 
               
               
                   
                   
                   
                   
                   
                 transcription 
               
               
                   
                   
                   
                   
                   
                 factors 
               
               
                 PYGB 
                 Glycogen 
                 Phosphorylase 
                 C326 
                 yes 
                 Unknown 
               
               
                   
                 phosphorylase, 
                   
                   
                   
                   
               
               
                   
                 brain form 
                   
                   
                   
                   
               
               
                 RARS 
                 Arginine--tRNA 
                 tRNA binding 
                 C32 
                 yes 
                 Unknown 
               
               
                   
                 ligase, cytoplasmic 
                   
                   
                   
                   
               
               
                 SON 
                 Protein SON 
                 RNA/DNA binding 
                 C92 
                 yes 
                 Unknown 
               
               
                 SYNE2 
                 Nesprin-2 
                 Actin binding 
                 C553 
                 yes 
                 Unknown 
               
               
                 TDRKH 
                 Tudor and KH 
                 RNA binding 
                 C109 
                 yes 
                 Unknown 
               
               
                   
                 domain-containing 
                   
                   
                   
                   
               
               
                   
                 protein 
                   
                   
                   
                   
               
               
                 THNSL1 
                 Threonine synthase- 
                 Threonine synthase 
                 C324 
                 yes 
                 Unknown 
               
               
                   
                 like 1 
                   
                   
                   
                   
               
               
                 THOC1 
                 THO complex 
                 RNA/DNA binding 
                 C49 
                 yes 
                 Unknown 
               
               
                   
                 subunit 1 
                   
                   
                   
                   
               
               
                 TNFAIP3 
                 Tumor necrosis 
                 Ubiquitin-specific 
                 C54 
                 yes 
                 Inhibits NF-κB 
               
               
                   
                 factor alpha-induced 
                 protease 
                   
                   
                 signaling upon 
               
               
                   
                 protein 3 
                   
                   
                   
                 TCR-mediated T 
               
               
                   
                   
                   
                   
                   
                 cell activation 
               
               
                 UBR4 
                 E3 ubiquitin-protein 
                 Ubiquitin ligase 
                 C2554 
                 yes 
                 Unknown 
               
               
                   
                 ligase 
                   
                   
                   
                   
               
               
                 USP7 
                 Ubiquitin carboxyl- 
                 Ubiquitin-specific 
                 C315 
                 yes 
                 Deubiquitinates 
               
               
                   
                 terminal hydrolase 7 
                 protease 
                   
                   
                 FOXP3, 
               
               
                   
                   
                   
                   
                   
                 increasing Treg 
               
               
                   
                   
                   
                   
                   
                 suppressive 
               
               
                   
                   
                   
                   
                   
                 capacity 
               
               
                 VDAC3 
                 Voltage-dependent 
                 Mitochondrial 
                 C65 
                 yes 
                 Unknown 
               
               
                   
                 anion-selective 
                 outer membrane 
                   
                   
                   
               
               
                   
                 channel protein 
                 channel 
                   
                   
                   
               
               
                 VDAC3 
                 Voltage-dependent 
                 Voltage-gated 
                 C36 
                 yes 
                 Unknown 
               
               
                   
                 anion-selective 
                 anion channel 
                   
                   
                   
               
               
                   
                 channel protein 
                   
                   
                   
                   
               
               
                 ZC3HAV1 
                 Zinc finger CCCH- 
                 Poly(A) RNA 
                 C645 
                 yes 
                 Inhibits viral 
               
               
                   
                 type antiviral 
                 binding 
                   
                   
                 replication 
               
               
                   
                 protein 1 
                   
                   
                   
                   
               
               
                 ZNF346 
                 Zinc finger protein 
                 RNA binding 
                 C68 
                 yes 
                 Unknown 
               
               
                   
                 346 
                   
                   
                   
                   
               
               
                 AARS 
                 Alanine--tRNA 
                 Alanine-tRNA 
                 C773 
                 no 
                 Unknown 
               
               
                   
                 ligase, cytoplasmic 
                 ligase 
                   
                   
                   
               
               
                 APOBEC3C 
                 Probable DNA dC- 
                 Cytidine deaminase 
                 C130 
                 no 
                 Inhibits retrovirus 
               
               
                   
                 dU- editing enzyme 
                   
                   
                   
                 replication 
               
               
                 BCL2A1 
                 Bcl-2-related 
                 Scaffolding protein 
                 C55 
                 no 
                 Expression 
               
               
                   
                 protein A1 
                   
                   
                   
                 induced by 
               
               
                   
                   
                   
                   
                   
                 inflammatory 
               
               
                   
                   
                   
                   
                   
                 cytokines 
               
               
                 BCL2A1 
                 Bcl-2-related 
                 Scaffolding protein 
                 C19 
                 no 
                 Unknown 
               
               
                   
                 protein A1 
                   
                   
                   
                   
               
               
                 CHRAC1 
                 Chromatin 
                 Chromatin 
                 C55 
                 no 
                 Unknown 
               
               
                   
                 accessibility 
                 remodeling 
                   
                   
                   
               
               
                   
                 complex protein 1 
                   
                   
                   
                   
               
               
                 DCXR 
                 L-xylulose 
                 Xylulose reductase 
                 C244 
                 no 
                 Unknown 
               
               
                   
                 reductase 
                   
                   
                   
                   
               
               
                 GHDC 
                 GH3 domain- 
                 Uncharacterized 
                 C502 
                 no 
                 Unknown 
               
               
                   
                 containing protein 
                   
                   
                   
                   
               
               
                 IRAK4 
                 Interleukin-1 
                 Serine/threonine 
                 C13 
                 no 
                 Helps initiate 
               
               
                   
                 receptor-associated 
                 protein kinase 
                   
                   
                 innate immune 
               
               
                   
                 kinase 4 
                   
                   
                   
                 response by 
               
               
                   
                   
                   
                   
                   
                 promoting 
               
               
                   
                   
                   
                   
                   
                 ubiquitination of 
               
               
                   
                   
                   
                   
                   
                 IRAK1 upon TLR 
               
               
                   
                   
                   
                   
                   
                 activation. Also 
               
               
                   
                   
                   
                   
                   
                 implicated in T 
               
               
                   
                   
                   
                   
                   
                 cell activation 
               
               
                 NADSYN1 
                 Glutamine- 
                 NAD(+) synthase 
                 C428 
                 no 
                 Unknown 
               
               
                   
                 dependent NAD(+) 
                   
                   
                   
                   
               
               
                   
                 synthetase 
                   
                   
                   
                   
               
               
                 PGLS 
                 6-phospho- 
                 Hydrolysis of 6- 
                 C32 
                 no 
                 Unknown 
               
               
                   
                 gluconolactonase 
                 phosphogluconolactone 
                   
                   
                   
               
               
                 PRKDC 
                 DNA-dependent 
                 Serine/threonine 
                 C4045 
                 no 
                 Regulates DNA 
               
               
                   
                 protein kinase 
                 protein kinase 
                   
                   
                 damage response, 
               
               
                   
                 catalytic subunit 
                   
                   
                   
                 involved in V(D)J 
               
               
                   
                   
                   
                   
                   
                 recombination 
               
               
                 PUSL1 
                 tRNA pseudouridine 
                 Pseudouridine 
                 C292 
                 no 
                 Unknown 
               
               
                   
                 synthase-like 1 
                 synthase 
                   
                   
                   
               
               
                 RIN3 
                 Ras and Rab 
                 GTPase activator 
                 C942 
                 no 
                 Unknown 
               
               
                   
                 interactor 3 
                   
                   
                   
                   
               
               
                 SCLY 
                 Selenocysteine lyase 
                 Selenocysteine 
                 C22 
                 no 
                 Unknown 
               
               
                   
                   
                 lyase 
                   
                   
                   
               
               
                 SPCS2 
                 Signal peptidase 
                 Peptidase 
                 C17 
                 no 
                 Unknown 
               
               
                   
                 complex subunit 2 
                   
                   
                   
                   
               
               
                 TRNT1 
                 CCA tRNA 
                 tRNA binding 
                 C373 
                 no 
                 Mutations lead to 
               
               
                   
                 nucleotidyltransferase 
                   
                   
                   
                 B-cell 
               
               
                   
                 1, mitochondrial 
                   
                   
                   
                 immunodeficiency 
               
               
                   
                   
                   
                   
                   
                 as well as 
               
               
                   
                   
                   
                   
                   
                 progressive 
               
               
                   
                   
                   
                   
                   
                 reductions in T 
               
               
                   
                   
                   
                   
                   
                 and NK cells 
               
               
                   
                   
                   
                   
                   
                 (OMIM number 
               
               
                   
                   
                   
                   
                   
                 616084) 
               
               
                 TUBGCP3 
                 Gamma-tubulin 
                 Gamma-tubulin 
                 C194 
                 no 
                 Unknown 
               
               
                   
                 complex component 
                 binding 
                   
                   
                   
               
               
                   
                 3 
                   
                   
                   
                   
               
               
                 UBE2L6 
                 Ubiquitin/ISG 15- 
                 Ubiquitin- 
                 C98 
                 no 
                 Acts as an E2 
               
               
                   
                 conjugating enzyme 
                 conjugating 
                   
                   
                 enzyme for an 
               
               
                   
                 E2 L6 
                 enzyme 
                   
                   
                 IFN-induced 
               
               
                   
                   
                   
                   
                   
                 ubiquitin-like 
               
               
                   
                   
                   
                   
                   
                 protein 
               
               
                   
               
            
           
         
       
     
     Table 8 illustrates an exemplary list of DMF sensitive cysteine-containing proteins in human T cell targets. Table 8 further shows the accession number (or the protein identifier) of the protein. 
     
       
         
           
               
               
               
               
               
               
               
               
               
             
               
                   
               
               
                   
                   
                 SEQ 
                   
                   
                   
                   
                   
                   
               
               
                   
                   
                 ID 
                 DMF_50 
                 DMF_50 
                 DMF_50 
                 DMF_25 
                 DMF_10 
                 MMF_50 
               
               
                 Identifier 
                 Protein Name 
                 NO: 
                 μM_4 h 
                 μM_2 h 
                 μM_1 h 
                 μM_4 h 
                 μM_4h 
                 μM_4 h 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
               
               
               
               
               
            
               
                 Q9NRW3_C130 
                 APOBEC3C Probable DNA dC- 
                 805 
                 20 
                 20 
                 8.6 
                 — 
                 1.92 
                 1.48 
               
               
                   
                 dU-editing enzyme APOBEC-3C 
               
               
                 Q9NWZ3_C13 
                 IRAK4 Interleukin-1 receptor- 
                 806 
                 20 
                 — 
                 8.3 
                 — 
                 — 
                 1.48 
               
               
                   
                 associated kinase 4 
               
               
                 Q9Y2W6_C109 
                 TDRKH Tudor and KH domain- 
                 807 
                 20 
                 20 
                 4 
                 — 
                 2.34 
                 1.36 
               
               
                   
                 containing protein 
               
               
                 Q6IA69_C428 
                 NADSYN1 Glutamine-dependent 
                 808 
                 20 
                 2.31 
                 1.81 
                 — 
                 1.43 
                 1.33 
               
               
                   
                 NAD(+) synthetase 
               
               
                 O14920_C464 
                 IKBKB Inhibitor of nuclear factor 
                 809 
                 20 
                 10.12 
                 3.96 
                 — 
                 2.59 
                 — 
               
               
                   
                 kappa-B kinase subunit 
               
               
                 P00513_C75 
                 ADA Adenosine deaminase 
                 810 
                 20 
                 5.08 
                 2.51 
                 — 
                 2.29 
                 — 
               
               
                 Q9Y277_C65 
                 VDAC3 Voltage-dependent anion- 
                 811 
                 15.94 
                 7.53 
                 3.35 
                 5.64 
                 1.73 
                 1.39 
               
               
                   
                 selective channel protein 
               
               
                 P49588_C773 
                 AARS Alanine-t-RNA ligase, 
                 812 
                 12.75 
                 10.16 
                 9.34 
                 — 
                 2.84 
                 1.24 
               
               
                   
                 cytoplasmic 
               
               
                 O14933_C98 
                 UBE2L6 Ubiquitin/ISG15- 
                 813 
                 12.55 
                 2.92 
                 2.44 
                 — 
                 1.49 
                 1.7 
               
               
                   
                 conjugating enzyme E2 L6 
               
               
                 O95336_C32 
                 PGLS 6-phosphogluconolactonase 
                 814 
                 11.51 
                 9.49 
                 3.42 
                 5.32 
                 1.9 
                 1.26 
               
               
                 A6NDG6_C297 
                 PGP Phosphoglycolate phosphatase 
                 815 
                 10.77 
                 4.21 
                 3.06 
                 — 
                 — 
                 1.52 
               
               
                 Q7Z6Z7_C3372 
                 HUWE1 E3 ubiquitin-protein ligase 
                 816 
                 10.48 
                 4.43 
                 2.28 
                 — 
                 1.58 
                 1.2 
               
               
                   
                 HUWE1 
               
               
                 Q16548_C55 
                 BCL2A1 Bcl-2-related protein A1 
                 817 
                 7.18 
                 — 
                 — 
                 — 
                 — 
                 0.97 
               
               
                 P11216_C326 
                 PYGB Glycogen phosphorylase, 
                 818 
                 6.76 
                 3.73 
                 2.47 
                 3.53 
                 1.65 
                 1.29 
               
               
                   
                 brain form 
               
               
                 O95081_C39 
                 AGFG2 Arf-GAP domain and FG 
                 819 
                 6.39 
                 3.85 
                 — 
                 — 
                 1.42 
                 1.24 
               
               
                   
                 repeat-containing protein 2 
               
               
                 Q7Z2W4_C645 
                 ZC3HAV1 Zinc finger CCCH-type 
                 820 
                 6.28 
                 3.13 
                 2.36 
                 2.52 
                 1.46 
                 1.3 
               
               
                   
                 antiviral protein 1 
               
               
                 O00170_C122 
                 AIP AH receptor-interacting protein 
                 821 
                 6.14 
                 3.05 
                 — 
                 — 
                 — 
                 1.24 
               
               
                 Q96Q11_C373 
                 TRNT1 CCA tRNA 
                 822 
                 5.83 
                 2.66 
                 1.97 
                 — 
                 — 
                 1.29 
               
               
                   
                 nucleotidyltransferase 1, 
               
               
                   
                 mitochondrial 
               
               
                 Q8TB24_C942 
                 RIN3 Ras and Rab interactor 3 
                 823 
                 5.7 
                 3 
                 — 
                 — 
                 — 
                 1.23 
               
               
                 Q9Y4W2_C456 
                 LAS1L Ribosomal biogenesis 
                 824 
                 5.61 
                 3.42 
                 1.8 
                 — 
                 1.29 
                 1.14 
               
               
                   
                 protein LAS1L 
               
               
                 Q02556_C306 
                 IRF8 Interferon regulatory factor 8 
                 825 
                 5.32 
                 — 
                 1.66 
                 — 
                 1.9 
                 — 
               
               
                 Q96GW9_C425 
                 MARS2 Methionine--tRNA ligase, 
                 826 
                 5.3 
                 4.16 
                 2.23 
                 2.86 
                 1.84 
                 1.3 
               
               
                   
                 mitochondrial A 
               
               
                 Q15306_C194 
                 IRF4 Interferon regulatory factor 4 
                 827 
                 5.25 
                 3.13 
                 1.32 
                 1.78 
                 1.69 
                 1.33 
               
               
                 Q15005_C17 
                 SPCS2 Signal peptidase complex 
                 828 
                 5.09 
                 3.86 
                 2.25 
                 2.41 
                 1.42 
                 1.32 
               
               
                   
                 subunit 2 
               
               
                 P54136_C32 
                 RARS Arginine--tRNA ligase, cytoplasmic 
                 829 
                 5.02 
                 3.58 
                 2.58 
                 4.03 
                 0.62 
                 1.78 
               
               
                 Q96CW5_C194 
                 TUBGCP3 Gamma-tubulin complex 
                 830 
                 4.94 
                 2.44 
                 — 
                 — 
                 — 
                 — 
               
               
                   
                 component 3 
               
               
                 P46109_C249 
                 CRKL Crk-like protein 
                 831 
                 4.86 
                 3.21 
                 2.21 
                 — 
                 1.38 
                 1.27 
               
               
                 Q8N0Z8_C292 
                 PUSL1 tRNA pseudouridine 
                 832 
                 4.68 
                 — 
                 — 
                 — 
                 — 
                 1.36 
               
               
                   
                 synthase-like 1 
               
               
                 Q5T4S7_C2554 
                 UBR4 E3 ubiquitin-protein ligase 
                 833 
                 4.63 
                 2.1 
                 1.6 
                 — 
                 1.52 
                 1.2 
               
               
                   
                 UBR4 
               
               
                 Q9UL40_C68 
                 ZNF346 Zinc finger protein 346 
                 834 
                 4.6 
                 3.91 
                 2.5 
                 — 
                 1.98 
                 1.26 
               
               
                 Q13045_C46 
                 FLII Protein flightless-1 homolog 
                 835 
                 4.5 
                 3.57 
                 2.05 
                 — 
                 1.55 
                 1.27 
               
               
                 Q86YS7_C993 
                 KIAA0528 Uncharacterized protein 
                 836 
                 4.38 
                 — 
                 — 
                 — 
                 1.4 
                 1.4 
               
               
                   
                 KIAA0528 
               
               
                 Q9Y6C9_C296 
                 MITCH2 Mitochondrial carrier 
                 837 
                 4.3 
                 2.44 
                 1.81 
                 — 
                 1.68 
                 1.35 
               
               
                   
                 homolog 2 
               
               
                 Q7Z4W1_C244 
                 DCXR L-xylulose reductase 
                 838 
                 4.24 
                 2.76 
                 1.29 
                 — 
                 2.3 
                 — 
               
               
                 Q04759_C14 
                 PRKCQ Protein kinase C theta type 
                 839 
                 4.21 
                 2.92 
                 — 
                 3.29 
                 1.62 
                 1.14 
               
               
                 P18583_C92 
                 SON Protein SON 
                 840 
                 4.17 
                 6.31 
                 2.5 
                 — 
                 — 
                 1.31 
               
               
                 P31153_C56 
                 MAT2A S-adenosylmethionine 
                 841 
                 4.17 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                   
                 synthase isoform type-2 
               
               
                 Q16548_C19 
                 BCL2A1 Bcl-2-related protein A1 
                 842 
                 4.16 
                 2.09 
                 — 
                 2.19 
                 1.15 
                 1.28 
               
               
                 Q14005_C1004 
                 IL16 Pro-interleukin-16 
                 843 
                 4.13 
                 3.32 
                 1.95 
                 — 
                 1.37 
                 1.31 
               
               
                 P31153_C104 
                 MAT2A S-adenosylmethionine 
                 844 
                 4.11 
                 — 
                 — 
                 — 
                 1.5 
                 1.31 
               
               
                   
                 synthase isoform type-2 
               
               
                 Q9Y277_C36 
                 VDAC3 Voltage-dependent anion- 
                 845 
                 4.11 
                 3.98 
                 3.21 
                 — 
                 — 
                 1.18 
               
               
                   
                 selective channel protein 
               
               
                 Q8WXH0_C553 
                 SYNE2 Nesprin-2 
                 846 
                 4.05 
                 3.29 
                 — 
                 — 
                 1.61 
                 — 
               
               
                 Q96I15_C22 
                 SCLY Selenocysteine lyase 
                 847 
                 4.04 
                 2.16 
                 1.9 
                 2.16 
                 1.31 
                 1.27 
               
               
                 P29590_C479 
                 PML Protein PML 
                 848 
                 — 
                 4.57 
                 — 
                 2.17 
                 2.1 
                 1.27 
               
               
                 Q8IYQ7_C324 
                 THNSL1 Threonine synthase-like 1 
                 849 
                 — 
                 19.36 
                 15.93 
                 — 
                 — 
                 1.4 
               
               
                 Q93009_C315 
                 USP7 Ubiquitin carboxvy-terminal 
                 850 
                 — 
                 14.06 
                 5.33 
                 — 
                 1.9 
                 1.4 
               
               
                   
                 hydrolase 7 
               
               
                 P21580_C54 
                 TNFAIP3 Tumor necrosis factor 
                 851 
                 — 
                 5.34 
                 — 
                 — 
                 1.58 
                 — 
               
               
                   
                 alpha-induced protein 3 
               
               
                 O14976_C87 
                 GAK Cyclin-G-associated kinase 
                 852 
                 — 
                 4.79 
                 — 
                 — 
                 1.36 
                 — 
               
               
                 Q96FV9_C49 
                 THOC1 THO complex subunit 1 
                 853 
                 — 
                 5.7 
                 3.93 
                 — 
                 — 
                 0.97 
               
               
                 ki 
                   
                 854 
                 — 
                 10.53 
                 4.14 
                 — 
                 — 
                 1.23 
               
               
                 Q9NRG0_C55 
                 CHRAC1 Chromatin accessibility 
                 855 
                 — 
                 11.72 
                 12.59 
                 — 
                 5.07 
                 1.27 
               
               
                   
                 complex protein 1 
               
               
                 Q8N2G8_C502 
                 GHDC GH3 domain-containing 
                 856 
                 — 
                 20 
                 4.23 
                 — 
                 — 
                 — 
               
               
                   
                 protein 
               
               
                   
               
            
           
         
       
     
     Table 9 illustrates the full protein sequence of exemplary cysteine-containing proteins described herein. The cysteine residue of interest is denoted with (*). 
     
       
         
           
               
               
               
               
               
             
               
                   
               
               
                 Protein 
                   
                 Cysteine 
                   
                   
               
               
                 Identifier 
                   
                 Residue 
                   
                 SEQ 
               
               
                 (Accession No.) 
                 Protein Name 
                 Number 
                 Sequence 
                 ID NO: 
               
               
                   
               
             
            
               
                 O75874 
                 Isocitrate 
                 C269 
                 MSKKISGGSV VEMQGDEMTR IIWELIKEKL 
                 1 
               
               
                   
                 dehydrogenase 
                   
                 IFPYVELDLH SYDLGIENRD ATNDQVTKDA 
                   
               
               
                   
                 1 (IDH1) 
                   
                 AEAIKKHNVG VKCATITPDE KRVEEFKLKQ 
                   
               
               
                   
                   
                   
                 MWKSPNGTIR NILGGTVFRE AIICKNIPRL 
                   
               
               
                   
                   
                   
                 VSGWVKPIII GRHAYGDQVR ATDFVVPGPG 
                   
               
               
                   
                   
                   
                 KVEITYTPSD GTQKVTYLVH NFEEGGGVAM 
                   
               
               
                   
                   
                   
                 GMYNQDKSIE DFAHSSFQMA LSKGWPLYLS 
                   
               
               
                   
                   
                   
                 TKNTILKKYD GRFKDIFQEI YDKQYKSQFE 
                   
               
               
                   
                   
                   
                 AQKIWYEHRL IDDMVAQAMK SEGGFIWAC*K 
                   
               
               
                   
                   
                   
                 NYDGDVQSDS VAQGYGSLGM MTSVLVCPDG 
                   
               
               
                   
                   
                   
                 KTVEAEAAHG TVTRHYRMYQ KGQETSTNPI 
                   
               
               
                   
                   
                   
                 ASIFAWTRGL AHRAKLDNNK ELAFFANALE 
                   
               
               
                   
                   
                   
                 EVSIETIEAG FMTKDLAACI KGLPNVQRSD 
                   
               
               
                   
                   
                   
                 YLNTFEFMDK LGENLKIKLA QAKL 
                   
               
               
                   
               
               
                 P48735 
                 Isocitrate 
                 C308 
                 MAGYLRVVRS LCRASGSRPA WAPAALTAPT 
                 2 
               
               
                   
                 dehydrogenase 
                   
                 SQEQPRRHYA DKRIKVAKPV VEMDGDEMTR 
                   
               
               
                   
                 2 (IDH2) 
                   
                 IIWQFIKEKL ILPHVDIQLK YFDLGLPNRD 
                   
               
               
                   
                   
                   
                 QTDDQVTIDS ALATQKYSVA VKCATITPDE 
                   
               
               
                   
                   
                   
                 ARVEEFKLKK MWKSPNGTIR NILGGTVFRE 
                   
               
               
                   
                   
                   
                 PIICKNIPRL VPGWTKPITI GRHAHGDQYK 
                   
               
               
                   
                   
                   
                 ATDFVADRAG TFKMVFTPKD GSGVKEWEVY 
                   
               
               
                   
                   
                   
                 NFPAGGVGMG MYNTDESISG FAHSCFQYAI 
                   
               
               
                   
                   
                   
                 QKKWPLYMST KNTILKAYDG RFKDIFQEIF 
                   
               
               
                   
                   
                   
                 DKHYKTDFDK NKIWYEHRLI DDMVAQVLKS 
                   
               
               
                   
                   
                   
                 SGGFVWAC*KN YDGDVQSDIL AQGFGSLGLM 
                   
               
               
                   
                   
                   
                 TSVLVCPDGK TIEAEAAHGT VTRHYREHQK 
                   
               
               
                   
                   
                   
                 GRPTSTNPIA SIFAWTRGLE HRGKLDGNQD 
                   
               
               
                   
                   
                   
                 LIRFAQMLEK VCVETVESGA MTKDLAGCIH 
                   
               
               
                   
                   
                   
                 GLSNVKLNEH FLNTTDFLDT IKSNLDRALG 
                   
               
               
                   
                   
                   
                 RQ 
                   
               
               
                   
               
               
                 Q14790 
                 CASP8 
                 C360 
                 MDFSRNLYDI GEQLDSEDLA SLKFLSLDYI 
                 3 
               
               
                   
                   
                   
                 PQRKQEPIKD ALMLFQRLQE KRMLEESNLS 
                   
               
               
                   
                   
                   
                 FLKELLFRIN RLDLLITYLN TRKEEMEREL 
                   
               
               
                   
                   
                   
                 QTPGRAQISA YRVMLYQISE EVSRSELRSF 
                   
               
               
                   
                   
                   
                 KFLLQEEISK CKLDDDMNLL DIFIEMEKRV 
                   
               
               
                   
                   
                   
                 ILGEGKLDIL KRVCAQINKS LLKIINDYEE 
                   
               
               
                   
                   
                   
                 FSKERSSSLE GSPDEFSNGE ELCGVMTISD 
                   
               
               
                   
                   
                   
                 SPREQDSESQ TLDKVYQMKS KPRGYCLIIN 
                   
               
               
                   
                   
                   
                 NHNFAKAREK VPKLHSIRDR NGTHLDAGAL 
                   
               
               
                   
                   
                   
                 TTTFEELHFE IKPHDDCTVE QIYEILKIYQ 
                   
               
               
                   
                   
                   
                 LMDHSNMDCF ICCILSHGDK GIIYGTDGQE 
                   
               
               
                   
                   
                   
                 APIYELTSQF TGLKCPSLAG KPKVFFIQAC* 
                   
               
               
                   
                   
                   
                 QGDNYQKGIP VETDSEEQPY LEMDLSSPQT 
                   
               
               
                   
                   
                   
                 RYIPDEADFL LGMATVNNCV SYRNPAEGTW 
                   
               
               
                   
                   
                   
                 YIQSLCQSLR ERCPRGDDIL TILTEVNYEV 
                   
               
               
                   
                   
                   
                 SNKDDKKNMG KQMPQPTFTL RKKLVFPSD 
                   
               
               
                   
               
               
                 Q92851 
                 CASP10 
                 C401 
                 MKSQGQHWYS SSDKNCKVSF REKLLIIDSN 
                 4 
               
               
                   
                   
                   
                 LGVQDVENLK FLCIGLVPNK KLEKSSSASD 
                   
               
               
                   
                   
                   
                 VFEHLLAEDL LSEEDPFFLA ELLYIIRQKK 
                   
               
               
                   
                   
                   
                 LLQHLNCTKE EVERLLPTRQ RVSLFRNLLY 
                   
               
               
                   
                   
                   
                 ELSEGIDSEN LKDMIFLLKD SLPKTEMTSL 
                   
               
               
                   
                   
                   
                 SFLAFLEKQG KIDEDNLTCL EDLCKTVVPK 
                   
               
               
                   
                   
                   
                 LLRNIEKYKR EKAIQIVTPP VDKEAESYQG 
                   
               
               
                   
                   
                   
                 EEELVSQTDV KTFLEALPQE SWQNKHAGSN 
                   
               
               
                   
                   
                   
                 GNRATNGAPS LVSRGMQGAS ANTLNSETST 
                   
               
               
                   
                   
                   
                 KRAAVYRMNR NHRGLCVIVN NHSFTSLKDR 
                   
               
               
                   
                   
                   
                 QGTHKDAEIL SHVFQWLGFT VHIHNNVTKV 
                   
               
               
                   
                   
                   
                 EMEMVLQKQK CNPAHADGDC FVFCILTHGR 
                   
               
               
                   
                   
                   
                 FGAVYSSDEA LIPIREIMSH FTALQCPRLA 
                   
               
               
                   
                   
                   
                 EKPKLFFIQA C* QGEEIQPSV SIEADALNPE 
                   
               
               
                   
                   
                   
                 QAPTSLQDSI PAEADFLLGL ATVPGYVSFR 
                   
               
               
                   
                   
                   
                 HVEEGSWYIQ SLCNHLKKLV PRMLKFLEKT 
                   
               
               
                   
                   
                   
                 MEIRGRKRTV WGAKQISATS LPTAISAQTP 
                   
               
               
                   
                   
                   
                 RPPMRRWSSV S 
                   
               
               
                   
               
               
                 Q99873 
                 PRMT1 
                 C109 
                 MENFVATLAN GMSLQPPLEE VSCGQAESSE 
                 5 
               
               
                   
                   
                   
                 KPNAEDMTSK DYYFDSYAHF GIHEEMLKDE 
                   
               
               
                   
                   
                   
                 VRTLTYRNSM FHNRHLFKDK VVLDVGSGTG 
                   
               
               
                   
                   
                   
                 ILCMFAAKAG ARKVIGIEC* S SISDYAVKIV 
                   
               
               
                   
                   
                   
                 KANKLDHVVT IIKGKVEEVE LPVEKVDIII 
                   
               
               
                   
                   
                   
                 SEWMGYCLFY ESMLNTVLYA RDKWLAPDGL 
                   
               
               
                   
                   
                   
                 IFPDRATLYV TAIEDRQYKD YKIHWWENVY 
                   
               
               
                   
                   
                   
                 GFDMSCIKDV AIKEPLVDVV DPKQLVTNAC 
                   
               
               
                   
                   
                   
                 LIKEVDIYTV KVEDLTFTSP FCLQVKRNDY 
                   
               
               
                   
                   
                   
                 VHALVAYFNI EFTRCHKRTG FSTSPESPYT 
                   
               
               
                   
                   
                   
                 HWKQTVFYME DYLTVKTGEE IFGTIGMRPN 
                   
               
               
                   
                   
                   
                 AKNNRDLDFT IDLDFKGQLC ELSCSTDYRM 
                   
               
               
                   
                   
                   
                 R 
                   
               
               
                   
               
               
                 Q9NYL2 
                 MAP3 kinase 
                 C22 
                 MSSLGASFVQ IKFDDLQFFE NC*GGGSFGSV 
                 6 
               
               
                   
                 MLTK (or ZAK) 
                   
                 YRAKWISQDK EVAVKKLLKI EKEAEILSVL 
                   
               
               
                   
                   
                   
                 SHRNIIQFYG VILEPPNYGI VTEYASLGSL 
                   
               
               
                   
                   
                   
                 YDYINSNRSE EMDMDHIMTW ATDVAKGMHY 
                   
               
               
                   
                   
                   
                 LHMEAPVKVI HRDLKSRNVV IAADGVLKIC 
                   
               
               
                   
                   
                   
                 DFGASRFHNH TTHMSLVGTF PWMAPEVIQS 
                   
               
               
                   
                   
                   
                 LPVSETCDTY SYGVVLWEML TREVPFKGLE 
                   
               
               
                   
                   
                   
                 GLQVAWLVVE KNERLTIPSS CPRSFAELLH 
                   
               
               
                   
                   
                   
                 QCWEADAKKR PSFKQIISIL ESMSNDTSLP 
                   
               
               
                   
                   
                   
                 DKCNSFLHNK AEWRCEIEAT LERLKKLERD 
                   
               
               
                   
                   
                   
                 LSFKEQELKE RERRLKMWEQ KLTEQSNTPL 
                   
               
               
                   
                   
                   
                 LPSFEIGAWT EDDVYCWVQQ LVRKGDSSAE 
                   
               
               
                   
                   
                   
                 MSVYASLFKE NNITGKRLLL LEEEDLKDMG 
                   
               
               
                   
                   
                   
                 IVSKGHIIHF KSAIEKLTHD YINLFHFPPL 
                   
               
               
                   
                   
                   
                 IKDSGGEPEE NEEKIVNLEL VFGFHLKPGT 
                   
               
               
                   
                   
                   
                 GPQDCKWKMY MEMDGDEIAI TYIKDVTFNT 
                   
               
               
                   
                   
                   
                 NLPDAEILKM TKPPFVMEKW IVGIAKSQTV 
                   
               
               
                   
                   
                   
                 ECTVTYESDV RTPKSTKHVH SIQWSRTKPQ 
                   
               
               
                   
                   
                   
                 DEVKAVQLAI QTLFTNSDGN PGSRSDSSAD 
                   
               
               
                   
                   
                   
                 CQWLDTLRMR QIASNTSLQR SQSNPILGSP 
                   
               
               
                   
                   
                   
                 FFSHFDGQDS YAAAVRRPQV PIKYQQITPV 
                   
               
               
                   
                   
                   
                 NQSRSSSPTQ YGLTKNFSSL HLNSRDSGFS 
                   
               
               
                   
                   
                   
                 SGNTDTSSER GRYSDRSRNK YGRGSISLNS 
                   
               
               
                   
                   
                   
                 SPRGRYSGKS QHSTPSRGRY PGKFYRVSQS 
                   
               
               
                   
                   
                   
                 ALNPHQSPDF KRSPRDLHQP NTIPGMPLHP 
                   
               
               
                   
                   
                   
                 ETDSRASEED SKVSEGGWTK VENRKKPHRP 
                   
               
               
                   
                   
                   
                 SPAKTNKERA RGDHRGWRNF 
                   
               
               
                   
               
               
                 P12268 
                 IMPDH2 
                 C140, C331 
                 MADYLISGGT SYVPDDGLTA QQLFNCGDGL 
                 7 
               
               
                   
                   
                   
                 TYNDFLILPG YIDFTADQVD LTSALTKKIT 
                   
               
               
                   
                   
                   
                 LKTPLVSSPM DTVTEAGMAI AMALTGGIGF 
                   
               
               
                   
                   
                   
                 IHHNCTPEFQ ANEVRKVKKY EQGFITDPVV 
                   
               
               
                   
                   
                   
                 LSPKDRVRDV FEAKARHGFC* GIPITDTGRM 
                   
               
               
                   
                   
                   
                 GSRLVGIISS RDIDFLKEEE HDCFLEEIMT 
                   
               
               
                   
                   
                   
                 KREDLVVAPA GITLKEANEI LQRSKKGKLP 
                   
               
               
                   
                   
                   
                 IVNEDDELVA IIARTDLKKN RDYPLASKDA 
                   
               
               
                   
                   
                   
                 KKQLLCGAAI GTHEDDKYRL DLLAQAGVDV 
                   
               
               
                   
                   
                   
                 VVLDSSQGNS IFQINMIKYI KDKYPNLQVI 
                   
               
               
                   
                   
                   
                 GGNVVTAAQA KNLIDAGVDA LRVGMGSGSI 
                   
               
               
                   
                   
                   
                 C*ITQEVLACG RPQATAVYKV SEYARRFGVP 
                   
               
               
                   
                   
                   
                 VIADGGIQNV GHIAKALALG ASTVMMGSLL 
                   
               
               
                   
                   
                   
                 AATTEAPGEY FFSDGIRLKK YRGMGSLDAM 
                   
               
               
                   
                   
                   
                 DKHLSSQNRY FSEADKIKVA QGVSGAVQDK 
                   
               
               
                   
                   
                   
                 GSIHKFVPYL IAGIQHSCQD IGAKSLTQVR 
                   
               
               
                   
                   
                   
                 AMMYSGELKF EKRTSSAQVE GGVHSLHSYE 
                   
               
               
                   
                   
                   
                 KRLF 
                   
               
               
                   
               
               
                 Q9NQ88 
                 TIGAR 
                 C114, C161 
                 MARFALTVVR HGETRFNKEK IIQGQGVDEP 
                 8 
               
               
                   
                   
                   
                 LSETGFKQAA AAGIFLNNVK FTHAFSSDLM 
                   
               
               
                   
                   
                   
                 RTKQTMHGIL ERSKFCKDMT VKYDSRLRER 
                   
               
               
                   
                   
                   
                 KYGVVEGKAL SELRAMAKAA REEC*PVFTPP 
                   
               
               
                   
                   
                   
                 GGETLDQVKM RGIDFFEFLC QLILKEADQK 
                   
               
               
                   
                   
                   
                 EQFSQGSPSN C*LETSLAEIF PLGKNHSSKV 
                   
               
               
                   
                   
                   
                 NSDSGIPGLA ASVLVVSHGA YMRSLFDYFL 
                   
               
               
                   
                   
                   
                 TDLKCSLPAT LSRSELMSVT PNTGMSLFII 
                   
               
               
                   
                   
                   
                 NFEEGREVKP TVQCICMNLQ DHLNGLTETR 
                   
               
               
                   
               
               
                 Q04759 
                 PKCθ 
                 C14, C17 
                 MSPFLRIGLS NFDC*GSC*QSC QGEAVNPYCA 
                 9 
               
               
                   
                   
                   
                 VLNKEYVESE NGQMYIQKKP TMYPPWDSTF 
                   
               
               
                   
                   
                   
                 DAHINKGRVM QIIVKGKNVD LISETTVELY 
                   
               
               
                   
                   
                   
                 SLAERCRKNN GKTEIWLELK PQGRMLMNAR 
                   
               
               
                   
                   
                   
                 YFLEMSDTKD MNEFETEGFF ALHQRRGAIK 
                   
               
               
                   
                   
                   
                 QAKVHHVKCH EFTATFFPQP TFCSVCHEFV 
                   
               
               
                   
                   
                   
                 WGLNKQGYQC RQCNAAIHKK CIDKVIAKCT 
                   
               
               
                   
                   
                   
                 GSAINSRETM FHKERFKIDM PHRFKVYNYK 
                   
               
               
                   
                   
                   
                 SPTFCEHCGT LLWGLARQGL KCDACGMNVH 
                   
               
               
                   
                   
                   
                 HRCQTKVANL CGINQKLMAE ALAMIESTQQ 
                   
               
               
                   
                   
                   
                 ARCLRDTEQI FREGPVEIGL PCSIKNEARP 
                   
               
               
                   
                   
                   
                 PCLPTPGKRE PQGISWESPL DEVDKMCHLP 
                   
               
               
                   
                   
                   
                 EPELNKERPS LQIKLKIEDF ILHKMLGKGS 
                   
               
               
                   
                   
                   
                 FGKVFLAEFK KTNQFFAIKA LKKDVVLMDD 
                   
               
               
                   
                   
                   
                 DVECTMVEKR VLSLAWEHPF LTHMFCTFQT 
                   
               
               
                   
                   
                   
                 KENLFFVMEY LNGGDLMYHI QSCHKFDLSR 
                   
               
               
                   
                   
                   
                 ATFYAAEIIL GLQFLHSKGI VYRDLKLDNI 
                   
               
               
                   
                   
                   
                 LLDKDGHIKI ADFGMCKENM LGDAKTNTFC 
                   
               
               
                   
                   
                   
                 GTPDYIAPEI LLGQKYNHSV DWWSFGVLLY 
                   
               
               
                   
                   
                   
                 EMLIGQSPFH GQDEEELFHS IRMDNPFYPR 
                   
               
               
                   
                   
                   
                 WLEKEAKDLL VKLFVREPEK RLGVRGDIRQ 
                   
               
               
                   
                   
                   
                 HPLFREINWE ELERKEIDPP FRPKVKSPFD 
                   
               
               
                   
                   
                   
                 CSNFDKEFLN EKPRLSFADR ALINSMDQNM 
                   
               
               
                   
                   
                   
                 FRNFSFMNPG MERLIS 
               
               
                   
               
            
           
         
       
     
     Table 10A-Table 10E illustrate a list of cysteine containing proteins and potential cysteine site of conjugation separated by protein class. Table 10 Å illustrates cysteine containing enzymes and potential cysteine conjugation site. Table 10B shows a list of cysteine containing transcription factors and regulators. Table 10C shows an exemplary list of cysteine containing channels, transporters and receptors. Table 10D illustrates an exemplary cysteine containing adapter, scaffolding, and modulator protein. Table 10E provides an exemplary list of uncategorized cysteine containing proteins. 
     
       
         
           
               
               
               
               
             
               
                 TABLE 10A 
               
               
                   
               
               
                   
                   
                 Cysteine 
                 Protein 
               
               
                 Identifier 
                 Protein Name 
                 Location 
                 Class 
               
               
                   
               
             
            
               
                 O14920 
                 IKBKB Inhibitor of nuclear factor kappa-B kinase subunit 
                 C464 
                 Enzyme 
               
               
                 O14933 
                 UBE2L6 Ubiquitin/ISG15-conjugating enzyme E2 L6 PCTK 
                 C98 
                 Enzyme 
               
               
                 O94953 
                 KDM4B Lysine-specific demethylase 4B 
                 C694 
                 Enzyme 
               
               
                 P00813 
                 ADA Adenosine deaminase 
                 C75 
                 Enzyme 
               
               
                 P09211 
                 GSTP1 Glutathione S-transferase P 
                 C48 
                 Enzyme 
               
               
                 P15374 
                 UCHL3 Ubiquitin carboxyl-terminal hydrolase isozyme L3 
                 C95 
                 Enzyme 
               
               
                 P16455 
                 MGMT Methylated-DNA--protein-cysteine methyltransferase 
                 C145; 
                 Enzyme 
               
               
                   
                   
                 C150 
                   
               
               
                 P17812 
                 CTP synthase 1 
                 C491 
                 Enzyme 
               
               
                 P19447 
                 ERCC3 TFIIH basal transcription factor complex helicase 
                 C342 
                 Enzyme 
               
               
                 P21580 
                 TNFAIP3 Tumor necrosis factor alpha-induced protein 3 
                 C54 
                 Enzyme 
               
               
                 P24752 
                 ACAT1 Acetyl-CoA acetyltransferase, mitochondrial 
                 C119; 
                 Enzyme 
               
               
                   
                   
                 C126; 
                   
               
               
                   
                   
                 C196; 
                   
               
               
                   
                   
                 C413 
                   
               
               
                 P40261 
                 Nicotinamide N-methyltransferase 
                 C165 
                 Enzyme 
               
               
                 P41226 
                 UBA7 Ubiquitin-like modifier-activating enzyme 7 
                 C599 
                 Enzyme 
               
               
                 P42575 
                 CASP2 Caspase-2 
                 C370 
                 Enzyme 
               
               
                 P43403 
                 ZAP70 Tyrosine-protein kinase ZAP-70 
                 C117 
                 Enzyme 
               
               
                 P48735 
                 IDH2 Isocitrate dehydrogenase 
                 C308 
                 Enzyme 
               
               
                 P51617 
                 IRAKI Interleukin-1 receptor-associated kinase 1 
                 C608 
                 Enzyme 
               
               
                 P61081 
                 NEDD8-conjugating enzyme Ubc12 
                 C47 
                 Enzyme 
               
               
                 P61088 
                 Ubiquitin-conjugating enzyme E2 N 
                 C87 
                 Enzyme 
               
               
                 P68036 
                 UBE2L3 Ubiquitin-conjugating enzyme E2 L3 
                 C86 
                 Enzyme 
               
               
                 Q00535 
                 CDK5 Cyclin-dependent kinase 5 
                 C157 
                 Enzyme 
               
               
                 Q04759 
                 PRKCQ Protein kinase C theta type 
                 C14; C17 
                 Enzyme 
               
               
                 Q06124 
                 Tyrosine-protein phosphatase non-receptor type 11 
                 C573 
                 Enzyme 
               
               
                 Q09472 
                 EP300 Histone acetyltransferase p300 
                 C1738 
                 Enzyme 
               
               
                 Q14790 
                 CASP8 Caspase-8 
                 C360 
                 Enzyme 
               
               
                 Q15084 
                 PDIA6 Protein disulfide-isomerase A6 
                 C55; C58; 
                 Enzyme 
               
               
                   
                   
                 C190; 
                   
               
               
                   
                   
                 C193 
                   
               
               
                 Q15910 
                 EZH2 Histone-lysine N-methyltransferase EZH2 
                 C503 
                 Enzyme 
               
               
                 Q16763 
                 UBE2S Ubiquitin-conjugating enzyme E2 S 
                 C118 
                 Enzyme 
               
               
                 Q16822 
                 PCK2 Phosphoenolpyruvate carboxykinase 
                 C306 
                 Enzyme 
               
               
                 Q16875 
                 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 
                 C155 
                 Enzyme 
               
               
                 Q16877 
                 PFKFB4 6-phosphofructo-2-kinase/fructose-2,6-bisphosphata 
                 C159 
                 Enzyme 
               
               
                 Q6L8Q7 
                 PDE12 2,5-phosphodiesterase 12 
                 C108 
                 Enzyme 
               
               
                 Q70CQ2 
                 USP34 Ubiquitin carboxyl-terminal hydrolase 34 
                 C741; 
                 Enzyme 
               
               
                   
                   
                 C1090 
                   
               
               
                 Q86UV5 
                 USP48 Ubiquitin carboxyl-terminal hydrolase 48 
                 C39 
                 Enzyme 
               
               
                 Q92851 
                 Caspase-10 
                 C401 
                 Enzyme 
               
               
                 Q93009 
                 USP7 Ubiquitin carboxyl-terminal hydrolase 7 
                 C223; 
                 Enzyme 
               
               
                   
                   
                 C315 
                   
               
               
                 Q96FA3 
                 PELI1 E3 ubiquitin-protein ligase pellino homolog 1 
                 C282 
                 Enzyme 
               
               
                 Q96JH7 
                 VCPIP1 Deubiquitinating protein VCIP135 
                 C219 
                 Enzyme 
               
               
                 Q96RU2 
                 USP28 Ubiquitin carboxyl-terminal hydrolase 28 
                 C171; 
                 Enzyme 
               
               
                   
                   
                 C733 
                   
               
               
                 Q99873 
                 PRMT1 Protein arginine N-methyltransferase 1 
                 C109 
                 Enzyme 
               
               
                 Q9C0C9 
                 UBE2O Ubiquitin-conjugating enzyme E2 O 
                 C375 
                 Enzyme 
               
               
                 Q9NRW4 
                 Dual specificity protein phosphatase 22 
                 C124 
                 Enzyme 
               
               
                 Q9NWZ3 
                 IRAK4 Interleukin-1 receptor-associated kinase 4 
                 C13 
                 Enzyme 
               
               
                 Q9NYL2 
                 MLTK Mitogen-activated protein kinase kinase kinase MLT 
                 C22 
                 Enzyme 
               
               
                 Q9UPT9 
                 USP22 Ubiquitin carboxyl-terminal hydrolase 22 
                 C44; 
                 Enzyme 
               
               
                   
                   
                 C171 
                   
               
               
                 Q9Y3Z3 
                 SAMHD1 SAM domain and HD domain-containing protein 1 
                 C522 
                 Enzyme 
               
               
                 Q9Y4C1 
                 KDM3A Lysine-specific demethylase 3A 
                 C251 
                 Enzyme 
               
               
                 Q9Y5T5 
                 USP16 Ubiquitin carboxyl-terminal hydrolase 16 
                 C205 
                 Enzyme 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
             
               
                 TABLE 10B 
               
               
                   
               
               
                   
                   
                 Cysteine 
                   
               
               
                 Identifier 
                 Protein Name 
                 Location 
                 Protein Class 
               
               
                   
               
             
            
               
                 O75362 
                 ZNF217 Zinc finger protein 217 
                 C286 
                 Transcription 
               
               
                   
                   
                   
                 factors and 
               
               
                   
                   
                   
                 regulators 
               
               
                 P04150 
                 NR3C1 Glucocorticoid receptor 
                 C302; C622 
                 Transcription 
               
               
                   
                   
                   
                 factors and 
               
               
                   
                   
                   
                 regulators 
               
               
                 P09086 
                 POU2F2 POU domain, class 2, transcription factor 2 
                 C346 
                 Transcription 
               
               
                   
                   
                   
                 factors and 
               
               
                   
                   
                   
                 regulators 
               
               
                 P40763 
                 STAT3 Signal transducer and activator of transcription 3 
                 C259 
                 Transcription 
               
               
                   
                   
                   
                 factors and 
               
               
                   
                   
                   
                 regulators 
               
               
                 P48200 
                 IREB2 Iron-responsive element-binding protein 2 
                 C137 
                 Transcription 
               
               
                   
                   
                   
                 factors and 
               
               
                   
                   
                   
                 regulators 
               
               
                 Q01201 
                 RELB Transcription factor RelB 
                 C109 
                 Transcription 
               
               
                   
                   
                   
                 factors and 
               
               
                   
                   
                   
                 regulators 
               
               
                 Q02556 
                 IRF8 Interferon regulatory factor 8 
                 C306 
                 Transcription 
               
               
                   
                   
                   
                 factors and 
               
               
                   
                   
                   
                 regulators 
               
               
                 Q15306 
                 IRF4 Interferon regulatory factor 4 
                 C194 
                 Transcription 
               
               
                   
                   
                   
                 factors and 
               
               
                   
                   
                   
                 regulators 
               
               
                 Q7Z2W4 
                 ZC3HAV1 Zinc finger CCCH-type antiviral protein 1 
                 C645 
                 Transcription 
               
               
                   
                   
                   
                 factors and 
               
               
                   
                   
                   
                 regulators 
               
               
                 Q8TAQ2 
                 SMARCC2 SWI/SNF complex subunit SMARCC2 
                 C145 
                 Transcription 
               
               
                   
                   
                   
                 factors and 
               
               
                   
                   
                   
                 regulators 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
             
               
                 TABLE 10C 
               
               
                   
               
               
                   
                   
                 Cysteine 
                   
               
               
                 Identifier 
                 Protein Name 
                 Location 
                 Protein Class 
               
               
                   
               
             
            
               
                 P63244 
                 GNB2L1 Guanine nucleotide-binding protein subunit 
                 C182 
                 Channels, 
               
               
                   
                 beta-2-like 1 
                   
                 Transporters, 
               
               
                   
                   
                   
                 Receptors 
               
               
                 Q16186 
                 Proteasomal ubiquitin receptor ADRM1 
                 C88 
                 Channels, 
               
               
                   
                   
                   
                 Transporters, 
               
               
                   
                   
                   
                 Receptors 
               
               
                 Q9HB90 
                 RRAGC Ras-related GTP-binding protein C 
                 C358; C377 
                 Channels, 
               
               
                   
                   
                   
                 transporters, 
               
               
                   
                   
                   
                 and receptors 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
             
               
                 TABLE 10D 
               
               
                   
               
               
                   
                   
                 Cysteine 
                   
               
               
                 Identifier 
                 Protein Name 
                 Location 
                 Protein Class 
               
               
                   
               
             
            
               
                 P14598 
                 NCF1 Neutrophil cytosol factor 1 
                 C378 
                 Adapter, 
               
               
                   
                   
                   
                 scaffolding, 
               
               
                   
                   
                   
                 modulator 
               
               
                   
                   
                   
                 proteins 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
             
               
                 TABLE 10E 
               
               
                   
               
               
                   
                   
                 Cysteine 
                   
               
               
                 Identifier 
                 Protein Name 
                 Location 
                 Protein Class 
               
               
                   
               
             
            
               
                 O00170 
                 AIP AH receptor-interacting protein 
                 C122 
                 Uncategorized 
               
               
                 O00541 
                 PES1 Pescadillo homolog 
                 C272; C361 
                 Uncategorized 
               
               
                 O00622 
                 CYR61 Protein CYR61 
                 C39; C70; C134 
                 Uncategorized 
               
               
                 O14980 
                 XPO1 Exportin-1 
                 C34; C528; 
                 Uncategorized 
               
               
                   
                   
                 C1070 
                   
               
               
                 P50851 
                 LRBA Lipopolysaccharide-responsive and beige- 
                 C1704; C2675 
                 Uncategorized 
               
               
                   
                 like anchor protein 
                   
                   
               
               
                 Q96GG9 
                 DCUN1D1 DCN1-like protein 1 
                 C115 
                 Uncategorized 
               
               
                   
               
            
           
         
       
     
     The examples and embodiments described herein are for illustrative purposes only and various modifications or changes suggested to persons skilled in the art are to be included within the spirit and purview of this application and scope of the appended claims.