# Patent

## Title
Crystallization and structure of a plant peptide deformylase

## Abstract

This invention relates to the crystal structure of a plant peptide deformylase polypeptide and methods of using the structure to design compounds that modulate the activity of the polypeptide.

## Background
CROSS REFERENCE TO RELATED APPLICATIONS
This application is a divisional of U.S. application Ser. No. 11/542,989, filed Oct. 3, 2006, which claims priority to U.S. Provisional Application Ser. No. 60/835,823 filed Aug. 4, 2006, the entire contents of which are herein expressly incorporated herein by reference.


STATEMENTS REGARDING FEDERALLY SPONSORED RESEARCH
The invention was funded in part by Grant No. MCB-MCB-0240165 awarded by the National Science Foundation (NSF). The government may have certain rights in the invention.


TECHNICAL FIELD
This invention relates to the crystallization and structure of plant peptide deformylase and methods of using the structure.
BACKGROUND
Peptide deformylase (DEF; EC 3.5.1.88) is a metallopeptidase that catalyzes the removal of an N-formyl group from N-formyl methionine, which is the initiating amino acid residue for prokaryotically translated proteins. DEF is an essential enzyme and mutations, deletions, or insertions in the DEF gene, or inhibition of enzymatic activity, are lethal to prokaryotic organisms. For decades DEF was believed to be exclusively restricted to prokaryotes because protein translation in eukaryotic organisms initiates with an unformylated methionine residue. The restriction to prokaryotic organisms and the essentiality of DEF have made this enzyme the molecular target of many research efforts directed towards the development of broad-spectrum antibiotics, which would have little or no mammalian toxicity. In 2000 the existence of DEF in the chloroplasts of higher plants was reported, and it was also discovered that actinonin, a potent inhibitor of DEF, was phytotoxic to all plant species. The lethality of actinonin to a wide range of plants, including many agriculturally significant weed species, suggests that DEF is an essential and highly conserved enzyme in plants, and inhibitors targeting this enzyme could potentially serve as a new class of broad-spectrum herbicides as well as selectable markers.
Accordingly, plant peptide deformylase (DEF) polypeptides provide an attractive target for crystallization and structural studies which can lead to the identification and synthesis of new broad-spectrum herbicides and selectable markers with high specificity towards plant DEF.
SUMMARY
Provided herein are crystalline forms of a peptide deformylase, and atomic coordinates derived therefrom, useful for designing and identifying compounds that modulate the activity of the peptide deformylase. Accordingly, in one embodiment, a crystalline form of a polypeptide comprising the amino acid residues of SEQ ID NO:1, is provided. In some aspects, the crystalline form includes a structure characterized by tetragonal space group symmetry P41212 and unit cell of dimensions a, b, and c. In some aspects, a is about 40 Å to about 60 Å, b is about 40 Å to about 60 Å, and c is about 120 Å to about 160 Å. In other aspects, α=β=γ=90°. In some aspects, the polypeptide is a peptide deformylase isolated from Arabidopsis thaliana. 
In some embodiments, the crystalline form includes a coordinated metal ion selected from the group of consisting of Fe, Zn, and Ni, and any combination thereof. In one aspect, the metal ion is coordinated by amino acid residues Cys171, His 213, and His217 of SEQ ID NO:1.
In another embodiment, a crystalline form of a polypeptide including a structure defined by one or more structure coordinates of Arabidopsis thaliana peptide deformylase amino acid residues Gly121, Gly123, Leu124, Gln128, Glu169, Gly170, Cys171, Leu172, His213, Glu214, His 217, and Tyr178 according to Table 1, is provided. In general, structures derived from these crystalline forms encompass structures having coordinates that differ by a root mean square deviation of less than about 1.5 Å, 0.75 Å, or 0.35 Å, or any deviation in this range, when superimposed on the non-hydrogen atom positions of the corresponding atomic coordinates of Table 1. In some aspects, amino acid residues Gly121, Gly123, Leu124, Gln128, Glu169, Gly170, Cys171, Leu172, His213, Glu214, His217, and Tyr178 include the active site of the peptide deformylase. In some aspects, the polypeptide includes an amino acid sequence having at least 75%, at least 85%, or at least 95%, or any percent in this range, amino acid sequence identity to SEQ ID NO:1.
In other embodiments, a crystalline form of a polypeptide provided herein also includes a ligand complexed with the polypeptide. In some aspects, the ligand is a small molecule.
In another embodiment, a crystalline form of a polypeptide that includes the amino acid residues of SEQ ID NO:1 and an atomic structure characterized by the coordinates of Table 1, is provided.
In yet another embodiment, a machine-readable medium embedded with information that corresponds to a three-dimensional structural representation of a crystalline form of a polypeptide as provided herein.
In one embodiment, a computer system including a database containing information on the three dimensional structure of a crystalline form of an Arabidopsis thaliana peptide deformylase polypeptide and a user interface to view the information, is provided. In some aspects, the computer system includes information related to diffraction data obtained from a crystalline form comprising SEQ ID NO:1. In other aspects, the computer system of includes information related to an electron density map of a crystal comprising SEQ ID NO:1.
In another aspect, a computer system provided herein includes information related to the structure coordinates of Table 1 or homologous structure coordinates for the amino acid residues of SEQ ID NO:1 that have a root mean square deviation of non-hydrogen atoms of less than about 1.5 Å, 0.75 Å, 0.35 Å, or any percent in this range, when superimposed on the non-hydrogen atom positions of the corresponding atomic coordinates of Table 1.
In other aspects, a computer system provided herein includes information related to the structure coordinates for one or more amino acid residues Gly121, Gly123, Leu124, Gln128, Glu169, Gly170, Cys171, Leu172, His213, Glu214, His 217, and Tyr178 according to Table 1, or similar structure coordinates for the amino acids including a root mean square deviation of non-hydrogen atoms of less than about 1.5 Å, 0.75 Å, 0.35 Å, or any percent in this range, when superimposed on the non-hydrogen atom positions of the corresponding atomic coordinates of Table 1.
In another embodiment, a method of identifying a candidate compound that binds to the active site of Arabidopsis thaliana peptide deformylase polypeptide, is provided. The method includes comparing the atomic structure of the compound with a three-dimensional structure of a crystalline form of an Arabidopsis thaliana peptide deformylase polypeptide and computationally identifying a candidate compound for an ability to bind to the Arabidopsis thaliana peptide deformylase. In some aspects, the candidate compound binds to the active site of the Arabidopsis thaliana peptide deformylase. In other aspects, comparing the atomic structure of the compound with a three-dimensional structure of a crystalline form of an Arabidopsis thaliana peptide deformylase polypeptide includes employing a computational means to perform a fitting operation between the compound and at least one binding site of the peptide deformylase.
In some embodiments, the candidate compound identified by a computational method provided herein can be synthesized and screened for the ability to bind a plant peptide deformylase in vitro or in vivo. In some aspects, the compound is an herbicide.
In another embodiment, a method of identifying a candidate compound that binds to the active site of Arabidopsis thaliana peptide deformylase polypeptide, is provided. The method includes comparing the atomic structure of the compound with a three-dimensional structural representation of a crystalline form provided herein and computationally identifying a candidate compound for an ability to bind to the active site of Arabidopsis thaliana peptide deformylase.
In yet another embodiment, a method of computationally designing a candidate compound that binds to Arabidopsis thaliana peptide deformylase polypeptide, is provided. The method includes comparing the atomic structure of chemical entities, or fragments thereof, with a three-dimensional structural representation of a crystalline form of a polypeptide provided herein; identifying chemical entities capable of associating with the three-dimensional structural representation of a crystalline form of a polypeptide; and assembling the chemical entities, or fragments thereof, into a single molecule to provide the structure of the candidate compound. In some aspects, the candidate compound binds to the active site of Arabidopsis thaliana peptide deformylase.
In another embodiment, a method of identifying a region of Arabidopsis thaliana peptide deformylase polypeptide that contacts a compound, is provided. The method includes obtaining X-ray diffraction data for a crystal of Arabidopsis thaliana peptide deformylase; obtaining X-ray diffraction data for a complex of a Arabidopsis thaliana peptide deformylase and the compound; subtracting the X-ray diffraction data from the peptide deformylase with the X-ray diffraction data obtained from the complex to obtain the difference in the X-ray diffraction data; obtaining phases that correspond to X-ray diffraction data obtained for the peptide deformylase; correlating the data to generate a difference Fourier image of the compound; and locating the region of Arabidopsis thaliana peptide deformylase contacted by the compound. In some aspects, the compound is actinonin.
In another embodiment, a method of modifying an inhibitor of Arabidopsis thaliana peptide deformylase activity, is provided. The method includes obtaining a crystal including an Arabidopsis thaliana peptide deformylase polypeptide and an inhibitor; obtaining the atomic coordinates of the crystal; correlating the atomic coordinate data with one or more molecular modeling techniques; identifying at least one modification predicted to effect the interaction of the inhibitor with the polypeptide; and modifying the inhibitor based on the prediction. In one aspect, the modification is a computer generated modification. In other aspects, the modification is a physical modification made to the structure of the inhibitor. In one aspect, the crystal comprises the amino acid residues of SEQ ID NO:1.
In other aspects, the one or more molecular modeling techniques are selected from the group consisting of graphic molecular modeling and computational chemistry. In another aspect, obtaining the atomic coordinates of the crystal includes detecting the interaction of the inhibitor to one or more amino acid residues Gly121, Gly123, Leu124, Gln128, Glu169, Gly170, Cys171, Leu172, His213, Glu214, His217, and Tyr178 of SEQ ID NO:1.
The details of one or more embodiments of the disclosure are set forth in the accompanying drawings and the description below. Other features, objects, and advantages will be apparent from the description and drawings, and from the claims.



BRIEF DESCRIPTION OF DRAWINGS
FIG. 1A depicts a polyacrylamide gel showing that limited trypsinolysis creates a core protein that retained activity and remained soluble in the absence of high salt concentrations.
FIG. 1B depicts the amino acid sequence of the AtDEF peptide (SEQ ID NO: 1).
FIG. 2A depicts a ribbon representation of crystallized AtDEF2. The cylinders represent helices and the arrows represent sheets.
FIG. 2B depicts a slab view of the ribbon representation of trypsinolyzed AtDEF2 highlighting the active-site-metal binding ligands (1 Cys and 2 His) from motifs II and III, respectively (EGCLS (SEQ ID NO: 15) and QHEXXH (SEQ ID NO: 16)).
FIG. 3 depicts a graph of substrate specificity comparison of AtDEF1 and AtDEF2.
FIG. 4 depicts a comparison of amino acid sequence conservation of the three motifs in AtDEF1 and 2 and bacterial DEFs (SEQ ID NOS: 2-5).
FIG. 5 depicts a molecular model of the N-terminal residues from the D1 polypeptide docked into the active site of Arabidopsis thaliana peptide deformylase.
FIG. 6 depicts a phylogenetic analyses comparing Motif 1 (SEQ ID NO: 6), Motif 2 (SEQ ID NO:7) and Motif 3 (SEQ ID NO: 8) of plant AtDEF1 peptide deformylase with the amino acid sequence of other peptide deformylase sequences.
FIG. 7 depicts a phylogenetic analyses comparing Motif 1 (SEQ ID NO: 9), Motif 2 (SEQ ID NO: 10) and Motif 3 (SEQ ID NO: 11) of plant AtDEF2 peptide deformylase with the amino acid sequence of other peptide deformylase sequences.
FIG. 8 depicts a phylogenetic analyses comparing Motif 1 (SEQ ID NO: 12), Motif 2 (SEQ ID NO: 13) and Motif 3 (SEQ ID NO: 14) of various peptide deformylase amino acid sequences.



Like reference symbols in the various drawings indicate like elements.
DETAILED DESCRIPTION
Provided herein are novel crystalline forms of peptide deformylase polypeptides and atomic coordinate information related to such crystals. Also provided are methods of using such information to identify, design and/or modify compounds that modulate the activity of a peptide deformylase. In addition, computer systems that include such information are provided. The crystal structures and information derived therefrom are suitable for designing and identifying, for example, broad spectrum herbicides. Such herbicides can be used, for example, to inhibit or prevent the growth of undesirable vegetation.
The crystal structure is based, at least in part, on the discovery of a plant nuclear gene that encodes a chloroplast targeted peptide deformylase polypeptide. The gene has substantial homology to bacterial peptide deformylase. The deduced translation of this nucleic acid sequence reveals the presence of three conserved protein motifs associated with prokaryotic peptide deformylase (see e.g., FIGS. 6, 7, and 8). Nucleic acid and amino acid sequences for plant peptide deformylases are disclosed in U.S. Pat. No. 6,730,634, issued May 4, 2004, and U.S. Patent Application Publication No. 20040088755, the contents of which are incorporated herein by reference.
It is to be understood that the crystalline form of a plant peptide deformylase from which the atomic structure coordinates of the invention can be obtained is not limited to wild-type Arabidopsis thaliana peptide deformylase polypeptide, or a truncated form of the polypeptide (see e.g., SEQ ID NO:1) as provided herein. Indeed, the crystals may comprise mutants of wild-type Arabidopsis thaliana peptide deformylase or the sequence of amino acids set forth in SEQ ID NO:1. Mutants can be obtained by replacing at least one amino acid residue in the sequence of the wild-type Arabidopsis thaliana peptide deformylase or the sequence of amino acids set forth in SEQ ID NO:1 with a different amino acid residue, or by adding or deleting one or more amino acid residues within the wild-type sequence and/or at the N- and/or C-terminus of the wild-type Arabidopsis thaliana peptide deformylase or the sequence of amino acids set forth in SEQ ID NO:1. Preferably, such mutants will crystallize under crystallization conditions that are substantially similar to those used to crystallize the wild-type Arabidopsis thaliana peptide deformylase or the sequence of amino acids set forth in SEQ ID NO:1.
The types of mutants contemplated by this invention include conservative mutants, non-conservative mutants, deletion mutants, truncated mutants, extended mutants, methionine mutants, selenomethionine mutants, cysteine mutants and selenocysteine mutants. A mutant may have, but need not have, Arabidopsis thaliana peptide deformylase activity. Preferably, a mutant displays biological activity that is substantially similar to that of the wild-type polypeptide or that of SEQ ID NO:1.
It will be recognized by one of skill in the art that the types of mutants contemplated herein are not mutually exclusive; that is, for example, a polypeptide having a conservative mutation in one amino acid may in addition have a truncation of residues at the N-terminus.
In addition, conservative or non-conservative amino acid substitutions can be made to amino acids of wild-type Arabidopsis thaliana peptide deformylase or the sequence of amino acids set forth in SEQ ID NO:1 that are implicated in the active site of the polypeptide (e.g., amino acid residues Gly121, Gly123, Leu124, Gln128, Glu169, Gly170, Cys171, Leu172, His213, Glu214, His217, and Tyr178 of SEQ ID NO:1). Such conservative or non-conservative substitutions can affect, e.g., the affinity with which wild-type Arabidopsis thaliana peptide deformylase or the sequence of amino acids set forth in SEQ ID NO:1 binds to a substrate. In certain embodiments, the conservative or non-conservative amino acid substitutions can increase the affinity with which wild-type Arabidopsis thaliana peptide deformylase or the sequence of amino acids set forth in SEQ ID NO:1 binds to a substrate.
Conservative amino acid substitutions are well-known in the art, and include substitutions made on the basis of a similarity in polarity, charge, solubility, hydrophobicity and/or the hydrophilicity of the amino acid residues involved. Typical conservative substitutions are those in which the amino acid is substituted with a different amino acid that is a member of the same class or category, as those classes are defined herein. Thus, typical conservative substitutions include aromatic to aromatic, apolar to apolar, aliphatic to aliphatic, acidic to acidic, basic to basic, polar to polar, etc. Other conservative amino acid substitutions are well known in the art. It will be recognized by those of skill in the art that generally, a total of about 20% or fewer, typically about 10% or fewer, most usually about 5% or fewer, of the amino acids in the wild-type polypeptide sequence can be conservatively substituted with other amino acids without deleteriously affecting the biological activity and/or three-dimensional structure of the molecule, provided that such substitutions do not involve residues that are critical for activity. The following abbreviations are used for amino acids throughout this disclosure: A=Ala=Alanine, T=Thr=Threonine, V=Val=Valine, C=Cys=Cysteine, L=Leu=Leucine, Y=Tyr=Tyrosine, I=Ile=Isoleucine, N=Asn=Asparagine, P=Pro=Proline, Q=Gln=Glutamine, F=Phe=Phenylalanine, D=Asp=Aspartic Acid, W=Trp=Tryptophan, E=Glu=Glutamic Acid, M=Met=Methionine, K=Lys=Lysine, G=Gly=Glycine, R=Arg=Arginine, S=Ser=Serine, H=His=Histidine.
In some embodiments, it may be desirable to make mutations in the active site of a polypeptide, e.g., to reduce or completely eliminate deformylase activity. Mutations that will reduce or completely eliminate the activity of a particular protein will be apparent to those of skill in the art. For example, the amino acids identified in Table 1 could be mutated in order to reduce or eliminate the binding activity of wild-type Arabidopsis thaliana peptide deformylase or the sequence of amino acids set forth in SEQ ID NO:1.
The amino acid residue Cys (C) is unusual in that it can form disulfide bridges with other Cys (C) residues or other sulfhydryl-containing amino acids (“cysteine-like amino acids”). The ability of Cys (C) residues and other cysteine-like amino acids to exist in a polypeptide in either the reduced free —SH or oxidized disulfide-bridged form affects whether Cys (C) residues contribute net hydrophobic or hydrophilic character to a polypeptide.
While in most instances the amino acids of wild-type Arabidopsis thaliana peptide deformylase or the sequence of amino acids set forth in SEQ ID NO:1 will be substituted with genetically-encoded amino acids, in certain circumstances mutants may include genetically non-encoded amino acids. Alternatively, in instances where the mutant will be prepared in whole or in part by chemical synthesis, virtually any non-encoded amino acids may be used, ranging from D-isomers of the genetically encoded amino acids to non-encoded naturally-occurring natural and synthetic amino acids.
Conservative amino acid substitutions for many of the commonly known non-genetically encoded amino acids are well known in the art. Conservative substitutions for other non-encoded amino acids can be determined based on their physical properties as compared to the properties of the genetically encoded amino acids.
In some instances, it may be particularly advantageous or convenient to substitute, delete from and/or add amino acid residues to wild-type Arabidopsis thaliana peptide deformylase or the sequence of amino acids set forth in SEQ ID NO:1 in order to provide convenient cloning sites in cDNA encoding the polypeptide, to aid in purification of the polypeptide, etc. Such substitutions, deletions and/or additions that do not substantially alter the three dimensional structure of the native Arabidopsis thaliana peptide deformylase or the sequence of amino acids set forth in SEQ ID NO:1 will be apparent to those having skills in the art. These substitutions, deletions and/or additions include, but are not limited to, His tags, BirA tags, intein-containing self-cleaving tags, maltose binding protein fusions, glutathione S-transferase protein fusions, antibody fusions, green fluorescent protein fusions, signal peptide fusions, biotin accepting peptide fusions, and the like.
Mutations may also be introduced into a polypeptide sequence where there are residues, e.g., cysteine residues, that interfere with crystallization. Such cysteine residues can be substituted with an appropriate amino acid that does not readily form covalent bonds with other amino acid residues under crystallization conditions; e.g., by substituting the cysteine with Ala, Ser or Gly. Any cysteine located in a non-helical or non-beta-stranded segment, based on secondary structure assignments, are good candidates for replacement.
It should be noted that the mutants contemplated herein need not exhibit deformylase activity. Indeed, amino acid substitutions, additions or deletions that interfere with the binding activity of wild-type Arabidopsis thaliana peptide deformylase or the sequence of amino acids set forth in SEQ ID NO:1 are specifically contemplated by the invention. Such crystalline polypeptides, or the atomic structure coordinates obtained therefrom, can be used to provide phase information to aid the determination of the three-dimensional X-ray structures of other related or non-related crystalline polypeptides.
Also contemplated are homologs of the Arabidopsis thaliana peptide deformylase. The present invention provides a computer-assisted method for homology modeling an Arabidopsis thaliana peptide deformylase homolog including: aligning the amino acid sequence of an Arabidopsis thaliana peptide deformylase homolog with the amino acid sequence of Arabidopsis thaliana peptide deformylase SEQ ID NO:1 and incorporating the sequence of the Arabidopsis thaliana peptide deformylase homolog into a model of Arabidopsis thaliana peptide deformylase derived from structure coordinates set forth in Table 1 to yield a preliminary model of the Arabidopsis thaliana peptide deformylase homolog; subjecting the preliminary model to energy minimization to yield an energy minimized model; remodeling regions of the energy minimized model where stereochemistry restraints are violated to yield a final model of the Arabidopsis thaliana peptide deformylase homolog.
As used herein, the term “homolog” refers to the polypeptide molecule or the nucleic acid molecule which encodes the polypeptide, or a functional domain from said polypeptide from a first source having at least about 30%, 40% or 50% sequence identity, or at least about 60%, 70% or 75% sequence identity, or at least about 80% sequence identity, or more preferably at least about 85% sequence identity, or even more preferably at least about 90% sequence identity, and most preferably at least about 95%, 97% or 99% amino acid or nucleotide sequence identity, with the polypeptide, encoding nucleic acid molecule or any functional domain thereof, from a second source. The second source may be a version of the molecule from the first source that has been genetically altered by any available means to change the primary amino acid or nucleotide sequence or may be from the same or a different species than that of the first source. Homology modeling is further discussed below.
Accordingly, provided herein are crystalline forms of a plant peptide deformylase. Referring to FIG. 1A, limited trypsinolysis creates a core protein that retained activity and remained soluble in the absence of high salt concentrations. Analysis of wild-type and proteolyzed AtDEF2 on an 8-16% gradient SDS-PAGE. Trypsinolysis produces a truncated DEF2 with a mobility shift corresponding to a 3 kDa loss in molecular mass from AtDEF2, a 24.598 kDa enzyme. The truncated DEF2, which loses its hexahistidyl sequence, was subsequently separated from undigested DEF2 by loading the digested sample onto a HiTrap® affinity column (Amersham Pharmacia) and collecting the flowthrough. Undigested DEF2 remained bound to the column. Referring to FIG. 1B, the amino acid sequence of the truncated DEF2 polypeptide is provided.
It is understood that the term “crystalline form” includes a polypeptide associated with a plant peptide deformylase can include just the polypeptide, or the polypeptide complexed with a metal, a ligand, or any other chemical entity suitable for crystallization with the polypeptide. An exemplary polypeptide includes Arabidopsis thaliana peptide deformylase, or fragments thereof, suitable for crystallization. Such fragments include optionally, the crystal may include a coordinated metal ion selected from the group of consisting of Fe, Zn, Ni, or combinations thereof. Thus, “crystalline form” and “crystal” refer to a composition comprising a polypeptide complex in crystalline form. The term “crystal” includes native crystals, heavy-atom derivative crystals and poly-crystals. “Native Crystal” refers to a crystal wherein the polypeptide complex is substantially pure.
Referring to FIG. 2A, the crystal structure of DEF2 was determined by molecular replacement and refined to a resolution of 2.7 Å. “Molecular Replacement” refers to the method of calculating initial phases for a new crystal of a polypeptide whose structure coordinates are unknown by orienting and positioning a polypeptide whose structure coordinates are known within the unit cell of the new crystal so as to best account for the observed diffraction pattern of the new crystal. Phases are then calculated from the oriented and positioned polypeptide and combined with observed amplitudes to provide an approximate Fourier synthesis of the structure of the polypeptides comprising the new crystal (Jones et al., 1991, Acta Crystallogr. 47:753-70; Brunger et al., 1998, Acta Crystallogr. D. Biol. Crystallogr. 54:905-21).
The overall fold of the enzyme resembles the α+β conformation of known bacterial peptide deformylases, with an r.m.s deviation of about 1.04 Å on main chain atoms relative to the E. coli enzyme. The largest differences occur in the orientation of the C-terminal helix (helix 3) and the conformation of the loop between β strands 2 and 3, which form part of the five-stranded central sheet. Motif I, II and III are colored blue, green and pink, respectively. The active site metal, modeled as zinc due to the conditions of crystallization, is a space-filled sphere in the middle of the structure. Referring to FIG. 2B, a slab view of the ribbon representation of trypsinolyzed AtDEF2 highlighting the active-site-metal binding ligands (1 Cys and 2 His) from motifs II and III, respectively (EGCLS (SEQ ID NO: 2) and QHEXXH (SEQ ID NO: 3)) is provided. As used herein, the term “active site” refers to regions on a protein or a structural motif of a protein that are directly involved in the function or activity of the peptide deformylase.
As used herein, the terms “binding site” or “binding pocket” refer to a region of a polypeptide or a molecular complex comprising the polypeptide that, as a result of the primary amino acid sequence of the polypeptide and/or its three-dimensional shape, favorably associates with another chemical entity or compound including ligands or inhibitors.
The crystalline form can include the tetragonal space group symmetry P41212 and includes a unit cell having dimensions a, b, and c; wherein a is about 40 Å to about 60 Å, b is about 40 Å to about 60 Å, and c is about 120 Å to about 160 Å; and wherein alpha=beta=gamma=90 degree. In some aspects, a is about 49 Å to about 52 Å, b is about 49 Å to about 52 Å, and c is about 143 Å to about 147 Å.
“Unit Cell” refers to the smallest and simplest volume element (i.e., parallel piped-shaped block) of a crystal that is completely representative of the unit or pattern of the crystal, such that the entire crystal can be generated by translation of the unit cell. The dimensions of the unit cell are defined by six numbers: dimensions a, b and c and angles α, β and γ (Blundel et al., 1976, Protein Crystallography, Academic Press). A crystal is an efficiently packed array of many unit cells. “Tetragonal Unit Cell” refers to a unit cell in which a≠b≠c; and α=β=γ90°. “Crystal lattice” refers to the array of points defined by the vertices of packed unit cells. “Space group” refers to the set of symmetry operations of a unit cell. In a space group designation (e.g., C2) the capital letter indicates the lattice type and the other symbols represent symmetry operations that can be carried out on the unit cell without changing its appearance. “Asymmetric Unit” refers to the largest aggregate of molecules in the unit cell that possesses no symmetry elements that are part of the space group symmetry, but that can be juxtaposed on other identical entities by symmetry operations.
When a crystal is placed in an X-ray beam, the incident X-rays interact with the electron cloud of the molecules that make up the crystal, resulting in X-ray scatter. The combination of X-ray scatter with the lattice of the crystal gives rise to nonuniformity of the scatter; areas of high intensity are called diffracted X-rays. The angle at which diffracted beams emerge from the crystal can be computed by treating diffraction as if it were reflection from sets of equivalent, parallel planes of atoms in a crystal (Bragg's Law). The most obvious sets of planes in a crystal lattice are those that are parallel to the faces of the unit cell. These and other sets of planes can be drawn through the lattice points. Each set of planes is identified by three indices, hkl. The h index gives the number of parts into which the a edge of the unit cell is cut, the k index gives the number of parts into which the b edge of the unit cell is cut, and the l index gives the number of parts into which the c edge of the unit cell is cut by the set of hkl planes. Thus, for example, the 235 planes cut the a edge of each unit cell into halves, the b edge of each unit cell into thirds, and the c edge of each unit cell into fifths. Planes that are parallel to the bc face of the unit cell are the 100 planes; planes that are parallel to the ac face of the unit cell are the 010 planes; and planes that are parallel to the ab face of the unit cell are the 001 planes.
When a detector is placed in the path of the diffracted X-rays, in effect cutting into the sphere of diffraction, a series of spots, or reflections, are recorded to produce a “still” diffraction pattern. Each reflection is the result of X-rays reflecting off one set of parallel planes, and is characterized by an intensity, which is related to the distribution of molecules in the unit cell, and hkl indices, which correspond to the parallel planes from which the beam producing that spot was reflected. If the crystal is rotated about an axis perpendicular to the X-ray beam, a large number of reflections is recorded on the detector, resulting in a diffraction pattern.
The unit cell dimensions and space group of a crystal can be determined from its diffraction pattern. First, the spacing of reflections is inversely proportional to the lengths of the edges of the unit cell. Therefore, if a diffraction pattern is recorded when the X-ray beam is perpendicular to a face of the unit cell, two of the unit cell dimensions may be deduced from the spacing of the reflections in the x and y directions of the detector, the crystal-to-detector distance, and the wavelength of the X-rays. Those of skill in the art will appreciate that, in order to obtain all three unit cell dimensions, the crystal can be rotated such that the X-ray beam is perpendicular to another face of the unit cell. Second, the angles of a unit cell can be determined by the angles between lines of spots on the diffraction pattern. Third, the absence of certain reflections and the repetitive nature of the diffraction pattern, which may be evident by visual inspection, indicate the internal symmetry, or space group, of the crystal. Therefore, a crystal may be characterized by its unit cell and space group, as well as by its diffraction pattern.
Once the dimensions of the unit cell are determined, the likely number of polypeptides in the asymmetric unit can be deduced from the size of the polypeptide, the density of the average protein, and the typical solvent content of a protein crystal, which is usually in the range of 30-70% of the unit cell volume (Matthews, 1968, J. Mol. Biol. 33:491-497).
The diffraction pattern of a crystal is related to the three-dimensional shape of the molecules that constitute the crystal by a Fourier transform. It has been established that diffraction patterns of a crystal can result from X-ray diffraction as well as Laue, electron or neutron diffraction. X-ray diffraction has been the most widely used methods for determining macromolecular structures. It is therefore used by way of illustration to discuss the processes of diffraction data collection and subsequent structure determination. The scope of the present invention is, however, by no means limited only to X-ray diffraction analyses of crystalline forms of polypeptides. After enough diffraction data are collected for a crystal, the process of determining the solution is in essence a re-focusing of the diffracted X-rays to produce a three-dimensional image of the molecule in the crystal. Since lenses capable of focusing X-ray radiation do not yet exist, the structure determination can be done via mathematical operations that simulate the re-focusing process.
“X-ray Diffraction” refers to a type of wave interference created when high energy X-ray radiation interacts with any obstruction in its traveling path. The obstruction is often in the form of a crystal of protein, nucleic acid, or inorganic compound. The electrons that surround the atoms in the crystal, rather than the atomic nuclei, are the entities which physically interact with the incoming X-ray photons. When X-ray radiation hits the atoms in a crystal, they make the electronic clouds of the atoms move as does any electromagnetic wave. The re-emitted X-ray radiation gives rise to constructive or destructive interferences. This phenomenon is called X-ray diffraction. In X-ray crystallography, the X-ray diffraction patterns of closely spaced lattices of atoms in the crystal are recorded and then analyzed to reveal the structural nature of the crystal. For example, the spacing between the crystal lattices can be determined using Bragg's law. X-ray diffraction is widely used in chemistry and biochemistry to determine the structures of an immense variety of molecules, including inorganic compounds, DNA and proteins. X-ray diffraction is commonly carried out using single crystals of a material, but if these are not available, microcrystalline powdered samples may also be used, although this requires different equipment. A detailed discussion on X-ray diffraction may be found in Chapter 4 in “Principles of Protein X-ray Crystallography” by Drenth, second edition 1999, Springer-Verlag Inc.
“Bragg's Law” refers to the principle that defines the diffraction conditions that give rise to constructive interferences. When the phase shift of the incident radiation is proportional to 2π, the condition can be expressed as: πλ=2d sin(θ), where n is an integer; λ is the wavelength of the X-ray radiation, or radiations caused by moving electrons, protons and neutrons; d is the spacing between the planes in the atomic lattice, and θ is the angle between the incident ray and the scattering planes.
“Crystallization” in the context of protein X-ray crystallography refers to the processes during which soluble proteins are transformed into their crystalline forms. Crystals of a protein can be grown out of its solution state under experimental conditions that allow controlled phase transition. Such experimental conditions include a mixture of multiple solutions that often contain an aqueous solution of the target protein, a solution of one or a mixture of precipitants, and one or more compounds that contribute to the overall pH or ionic strength of the final mixture.
Provided herein are crystalline forms of a plant peptide deformylase polyepeptide, or a deformylase complexed with other molecules or chemical entities. Analysis of such crystalline forms of a polypeptide provides data in the form of structure coordinates. Exemplary structure coordinates for Arabidopsis thaliana peptide deformylase polypeptide are provided in Table 1. As used herein, the term “atomic coordinates” or “structure coordinates” refers to mathematical coordinates that describe the positions of atoms in crystals of a plant peptide deformylase in Protein Data Bank (PDB) format, including X, Y, Z and B, for each atom. The diffraction data obtained from the crystals are used to calculate an electron density map of the repeating unit of the crystal. The electron density maps may be used to establish the positions (i.e., coordinates X, Y and Z) of the individual atoms within the crystal. Those of skill in the art understand that a set of structure coordinates determined by X-ray crystallography is not without standard error. For the purpose of this invention, any set of structure coordinates for a plant peptide deformylse from any source having a root mean square deviation (r.m.s.d) of non-hydrogen atoms of less than about 1.5 Å when superimposed on the non-hydrogen atom positions of the corresponding atomic coordinates of Table 1 are considered substantially identical or homologous. Moreover, any set of structure coordinates for plant peptide deformylse from any source having a root mean square deviation of non-hydrogen atoms of less than about 0.75 Å when superimposed on the non-hydrogen atom positions of the corresponding atomic coordinates of Table 1 are considered substantially identical or homologous.
The term “root mean square deviation” means the square root of the arithmetic mean of the squares of the deviations. It is a way to express the deviation or variation from a trend or object. For purposes of this invention, the “root mean square deviation” defines the variation in the backbone of a protein from the backbone of a Arabidopsis thaliana peptide deformylase polypeptide or an active site portion thereof, as defined by the structure coordinates described herein. “Having substantially the same three-dimensional structure” refers to a polypeptide that is characterized by a set of atomic structure coordinates that have a root mean square deviation (r.m.s.d.) of less than or equal to about 1.5 Å when superimposed onto the atomic structure coordinates of Table 1 when at least about 50% to 100% of the C α atoms of the coordinates are included in the superposition.
Slight variations in structure coordinates can be generated by mathematically manipulating the plant peptide deformylase structure coordinates provided herein. For example, the structure coordinates set forth in Table 1 could be manipulated by crystallographic permutations of the structure coordinates, fractionalization of the structure coordinates, integer additions or subtractions to sets of the structure coordinates, inversion of the structure coordinates or any combination of the above. Alternatively, modifications in the crystal structure due to mutations, additions, substitutions, and/or deletions of amino acids, or other changes in any of the components that make up the crystal, could also yield variations in structure coordinates. Such slight variations in the individual coordinates will have little effect on overall shape. If such variations are within an acceptable standard error as compared to the original coordinates, the resulting three-dimensional shape is considered to be structurally equivalent. Thus, for the purpose of the structures provided herein, any active site, binding site or binding pocket defined by a set of structure coordinates for a polypeptide or for a homolog of a polypeptide from any source having a root mean square deviation of non-hydrogen atoms of less than about 1.5 Å when superimposed on the non-hydrogen atom positions of the corresponding atomic coordinates of Table 1, are considered substantially identical or homologous.
Active sites are of significant utility in the identification of compounds that specifically interact with, and modulate the activity of, a particular polypeptide. The association of natural ligands or substrates with the active sites of their corresponding receptors or enzymes is the basis of many biological mechanisms of action. Similarly, many compounds exert their biological effects through association with the active sites of receptors and enzymes. Such associations may occur with all or any parts of the active site. An understanding of such associations helps lead to the design of compounds that modulate the activity of their target. Therefore, this information is valuable in designing potential modifiers of plant peptide deformylase activity, as discussed in more detail below. For example, the structure of a substrate utilized by a particular deformylase can be used to design compounds that bind to an active site of a peptide deformylase. Referring to FIG. 3, substrate specificities for plant peptide deformylase AtDEF1 and AtDEF2 are shown. AtDEF1 and 2 activities are influenced by peptide substrate sequence. Peptide mimics of the N-termini of chloroplast-translated proteins, ribosomal protein S18 (f-MDKS), Rubisco LS (f-MSPQ), D1 (f-MTAI), PSI-I (f-MTTF), PSII-I (f-MLTL), and ATPase subunit III (f-MNPL) were tested as substrates. In addition to a control substrate for the assay (f-MAS), the formate-dehydrogenase-linked assay was performed with 4 mM substrate and either 1.2 mg AtDEF1 or 0.2 mg AtDEF2. The numbers above the grouped bars represent the ratio of AtDEF2 to AtDEF1 activities. (Dirk et al., Arch Biochem Biophys 406:135-141).
The term “active site (or binding pocket),” as used herein, refers to a region of a molecule or molecular complex, that, as a result of its shape, favorably associates with another chemical entity or compound. Thus, an active site may include or consist of features such as interfaces between domains. Chemical entities or compounds that may associate with an active site include, but are not limited to, compounds, ligands, cofactors, substrates, inhibitors, agonists, antagonists, etc.
An exemplary active site for a plant peptide deformylase is provided by amino acid residues Gly121, Gly123, Leu124, Gln128, Glu169, Gly170, Cys171, Leu172, His213, Glu214, His217, and Tyr178 of SEQ ID NO:1 and as shown in Table 1. Referring to FIG. 5, a model of the D1 N-terminus in AtDEF2's active site is provided. Potential H-bond highlighted between the Thr in the P2 position of the polypeptide substrate and a conserved AtDEF2 Tyr178 just carboxy terminal to motif II. The model was generated by taking a snapshot from a molecular dynamics simulation using AMBER. The total length of the simulation was 1 ns, and this snapshot is at 126 ps.
In general, the exemplary active site is defined by a set of points having a root mean square deviation of less than about 0.35 Å from points representing the backbone atoms of amino acids as represented by structure coordinates listed in Table 1. As noted above, the crystalline form optionally includes additional molecules such as a coordinated metal ion selected from the group of metals consisting of Fe, Zn, Ni and combinations thereof. In some aspects, the metal ion is coordinated by the amino acids Cys171, His213, and His217.
Also provided are scalable three-dimensional configuration of points, at least a portion of said points derived from structure coordinates of at least a portion of an Arabidopsis thaliana peptide deformylase molecule or molecular complex listed in Table 1 and having a root mean square deviation of about 1.04 Å from said structure coordinates. Preferably, at least a portion of the points are derived from the Arabidopsis thaliana peptide deformylase structure coordinates derived from structure coordinates representing the locations of at least the backbone atoms of a plurality of the amino acids defining at least one Arabidopsis thaliana peptide deformylase or Arabidopsis thaliana peptide deformylase-like active site, the active site including amino acids Gly121, Gly123, Leu124, Gln128, Glu169, Gly170, Cys171, Leu172, His213, Glu214, His217, and Tyr178.
The structure coordinates generated for a plant peptide deformylase, or an active site thereof, as shown in Table 1 define a unique configuration of points in space. Those of skill in the art understand that a set of structure coordinates for a polypeptide, or a polypeptide complexed with a chemical entity, or a portion thereof, define a relative set of points that, in turn, define a configuration in three dimensions. A similar or identical configuration can be defined by an entirely different set of coordinates, provided the distances and angles between coordinates remain essentially the same. Accordingly, the coordinates provided in Table 1 provide a “scalable” configuration of points that can be modified by increasing or decreasing the distances between coordinates by a scalar factor while keeping the angles essentially the same.
The atomic structure coordinates provided herein can be used in molecular modeling and design, as described more fully below. The present invention encompasses the structure coordinates and other information, e.g., amino acid sequence, connectivity tables, vector-based representations, temperature factors, etc., used to generate the three-dimensional structure of the plant peptide deformylase polypeptide for use in the software programs described below and other software programs.
The invention encompasses machine-readable media embedded with the three-dimensional structure of the model described herein, or with portions thereof. As used herein, “machine-readable medium” refers to any medium that can be read and accessed directly by a computer or scanner. Such media include, but are not limited to: magnetic storage media, such as floppy discs, hard disc storage medium and magnetic tape; optical storage media such as optical discs or CD-ROM; electrical storage media such as RAM or ROM; and hybrids of these categories such as magnetic/optical storage media. Such media further include paper on which is recorded a representation of the atomic structure coordinates, e.g., Cartesian coordinates, that can be read by a scanning device and converted into a three-dimensional structure with an OCR.
A variety of data storage structures are available to a skilled artisan for creating a computer readable medium having recorded thereon the atomic structure coordinates of the invention or portions thereof and/or X-ray diffraction data. The choice of the data storage structure will generally be based on the means chosen to access the stored information. In addition, a variety of data processor programs and formats can be used to store the sequence and X-ray data information on a computer readable medium. Such formats include, but are not limited to, Protein Data Bank (“PDB”) format (Research Collaboratory for Structural Bioinformatics; Cambridge Crystallographic Data Centre format; Structure-data (“SD”) file format (MDL Information Systems, Inc.; Dalby et al., 1992, J. Chem. Inf. Comp. Sci. 32:244-255), and line-notation, e.g., as used in SMILES (Weininger, 1988, J. Chem. Inf. Comp. Sci. 28:31-36). Methods of converting between various formats read by different computer software will be readily apparent to those of skill in the art, e.g., BABEL (v. 1.06, Walters & Stahl, .COPYRGT. 1992, 1993, 1994). All format representations of the polypeptide coordinates described herein, or portions thereof, are contemplated by the present invention. By providing computer readable medium having stored thereon the atomic coordinates of the invention, one of skill in the art can routinely access the atomic coordinates of the invention, or portions thereof, and related information for use in modeling and design programs, described in detail below.
While Cartesian coordinates are important and convenient representations of the three-dimensional structure of a polypeptide, those of skill in the art will readily recognize that other representations of the structure are also useful. Therefore, the three-dimensional structure of a polypeptide, as discussed herein, includes not only the Cartesian coordinate representation, but also all alternative representations of the three-dimensional distribution of atoms. For example, atomic coordinates may be represented as a Z-matrix, wherein a first atom of the protein is chosen, a second atom is placed at a defined distance from the first atom, a third atom is placed at a defined distance from the second atom so that it makes a defined angle with the first atom. Each subsequent atom is placed at a defined distance from a previously placed atom with a specified angle with respect to the third atom, and at a specified torsion angle with respect to a fourth atom. Atomic coordinates may also be represented as a Patterson function, wherein all interatomic vectors are drawn and are then placed with their tails at the origin. This representation is particularly useful for locating heavy atoms in a unit cell. In addition, atomic coordinates may be represented as a series of vectors having magnitude and direction and drawn from a chosen origin to each atom in the polypeptide structure. Furthermore, the positions of atoms in a three-dimensional structure may be represented as fractions of the unit cell (fractional coordinates), or in spherical polar coordinates.
Additional information, such as thermal parameters, which measure the motion of each atom in the structure, chain identifiers, which identify the particular chain of a multi-chain protein in which an atom is located, and connectivity information, which indicates to which atoms a particular atom is bonded, is also useful for representing a three-dimensional molecular structure.
Accordingly, also provided herein is a machine-readable data storage medium including a data storage material encoded with machine readable data which, when using a machine programmed with instructions for using the data, displays a graphical three-dimensional representation of at least one molecule or molecular complex selected from the group consisting of (i) a molecule or molecular complex including at least a portion of an Arabidopsis thaliana peptide deformylase or an Arabidopsis thaliana peptide deformylase-like active site including amino acids Gly121, Gly123, Leu124, Gln128, Glu169, Gly170, Cys171, Leu172, His213, Glu214, His217, and Tyr178 the active site being defined by a set of points having a root mean square deviation of less than about 1.5 Å from points representing the backbone atoms of the amino acids as represented by structure coordinates listed in Table 1.
Structure information, typically in the form of the atomic structure coordinates, can be used in a variety of computational or computer-based methods to, for example, design, screen for and/or identify compounds that bind the crystallized polypeptide or a portion or fragment thereof, or to intelligently design mutants that have altered biological properties, and the like. Three-dimensional modeling may be performed using the experimentally determined coordinates derived from X-ray diffraction patterns, such as those in Table 1, for example, wherein such modeling includes, but is not limited to, drawing pictures of the actual structures, building physical models of the actual structures, and determining the structures of related subunits and /ligand and subunit/ligand complexes using the coordinates. Such molecular modeling can utilize known X-ray diffraction molecular modeling algorithms or molecular modeling software to generate atomic coordinates corresponding to the three-dimensional structure of a plant peptide deformylase.
As described above, molecular modeling involves the use of computational methods, preferably computer assisted methods, to build realistic models of molecules that are identifiably related in sequence to the known crystal structure. It also involves modeling new small molecule inhibitors bound to a plant peptide deformylase starting with the structures of deformylase alone or complexed with known ligands or inhibitors. The methods utilized in ligand modeling range from molecular graphics (i.e., 3D representations) to computational chemistry (i.e., calculations of the physical and chemical properties) to make predictions about the binding of ligands or activities of ligands; to design new ligands; and to predict novel molecules, including ligands such as compounds that inhibit the activity of a plant deformylase. Such compounds may be useful as herbicides, for example.
One approach to rational design of a compound is to search for known molecular structures that might bind to an active site. Using molecular modeling, rational design programs can look at a range of different molecular structures of compounds that may fit into the active site of an enzyme or protein, and by moving them in a three-dimensional environment it can be decided which structures actually fit the site well. An alternate but related rational compound design approach starts with the known structure of a complex with a small molecule ligand and models modifications of that small molecule in an effort to make additional favorable interactions with peptide deformylase polypeptides, and/or the active site of such polypeptides.
The present invention includes the use of molecular and computer modeling techniques to design and select ligands, such as small molecule agonists or antagonists or other compounds that interact with peptide deformylase polypeptides. Such compounds include, but are not limited to, actinonin and derivatives thereof.
This invention also includes the design of compounds that act as uncompetitive inhibitors of at least one function of peptide deformylase polypeptides. These inhibitors may bind to all, or a portion of, the active sites or other regions of the polypeptide already bound to a ligand and may be more potent and less non-specific than competitive inhibitors that compete for active sites. Similarly, non-competitive inhibitors that bind to and inhibit at least one function of peptide deformylase polypeptides whether or not it is bound to another chemical entity, such as a natural ligand, for example, may be designed using the atomic coordinates of the chimeras or complexes comprising the chimeras of this invention.
The atomic coordinates of the present invention also provide the needed information to probe a crystal of a peptide deformylase polypeptide with molecules composed of a variety of different chemical features to determine optimal sites for interaction between candidate inhibitors and/or activators. For example, high resolution X-ray diffraction data collected from crystals saturated with solvent allows the determination of where each type of solvent molecule sticks. Small molecules that bind to those sites can then be designed and synthesized and tested for their inhibitory activity (Travis, J., Science 262:1374 (1993)).
The present invention also includes methods for computationally screening small molecule databases and libraries for chemical entities, agents, ligands, or compounds that can bind in whole, or in part, to peptide deformylase polypeptides. In this screening, the quality of fit of such entities or compounds to the binding site or sites may be judged either by shape complementarity or by estimated interaction energy (Meng, E. C. et al., J. Comp. Chem. 13:505-524 (1992)).
The design of compounds that bind to, promote or inhibit the functional activity of peptide deformylase polypeptides according to this invention generally involves consideration of two factors. First, the compound must be capable of physically and structurally associating with the peptide deformylase polypeptide. Non-covalent molecular interactions important in the association of the peptide deformylase polypeptide with the compound include hydrogen bonding, van der Waals and hydrophobic interactions. Second, the compound must be able to assume a conformation that allows it to associate with a peptide deformylase polypeptide. Although certain portions of the compound may not directly participate in the association with peptide deformylase polypeptide, those portions may still influence the overall conformation of the molecule. This, in turn, may have a significant impact on binding affinities and potency. Such conformational requirements include the overall three-dimensional structure and orientation of the chemical entity or compound in relation to all or a portion of the active site or other region of a peptide deformylase polypeptide, or the spacing between functional groups of a compound comprising several chemical entities that directly interact with a peptide deformylase polypeptide.
The potential, predicted, inhibitory agonist, antagonist or binding effect of a ligand or other compound on a peptide deformylase polypeptide may be analyzed prior to its actual synthesis and testing by the use of computer modeling techniques. If the theoretical structure of the given compound suggests insufficient interaction and association between it and the peptide deformylase polypeptide, synthesis and testing of the compound may be obviated. However, if computer modeling indicates a strong interaction, the molecule may then be synthesized and tested for its ability to interact with a peptide deformylase polypeptide. In this manner, synthesis of inoperative compounds may be avoided. In some cases, inactive compounds are synthesized predicted on modeling and then tested to develop a SAR (structure-activity relationship) for compounds interacting with a specific region of a peptide deformylase polypeptide.
One skilled in the art may use one of several methods to screen chemical entities fragments, compounds, or agents for their ability to associate with a peptide deformylase polypeptide and more particularly with the individual binding pockets or active sites of the peptide deformylase polypeptide. This process may begin by visual inspection of, for example, the active site based on the atomic coordinates of the polypeptide or the polypeptide complexed with a ligand. Selected chemical entities, compounds, or agents may then be positioned in a variety of orientations, or docked within an individual binding pocket of the peptide deformylase polypeptide. Docking may be accomplished using software-such as Quanta and Sybyl, followed by energy minimization and molecular dynamics with standard molecular mechanics forcefields, such as CHARMM and AMBER.
Specialized computer programs may also assist in the process of selecting chemical entities. These include but are not limited to: GRID (Goodford, P. J., “A Computational Procedure for Determining Energetically Favorable Binding Sites on Biologically Important Macromolecules,” J. Med. Chem. 28:849-857 (1985), available from Oxford University, Oxford, UK); MCSS (Miranker, A. and M. Karplus, “Functionality Maps of Binding Sites: A Multiple Copy Simultaneous Search Method.” Proteins: Structure, Function and Genetics 11: 29-34 (1991), available from Molecular Simulations, Burlington, Mass.); AUTODOCK (Goodsell, D. S, and A. J. Olsen, “Automated Docking of Substrates to Proteins by Simulated Annealing” Proteins: Structure. Function, and Genetics 8:195-202 (1990), available from Scripps Research Institute, La Jolla, Calif.); DOCK (Kuntz, I. D. et al., “A Geometric Approach to Macromolecule-Ligand Interactions,” J. Mol. Biol. 161:269-288 (1982), available from University of California, San Francisco, Calif.); Gold (Jones, G. et al., “Development and validation of a genetic algorithm for flexible docking.” J. Mol. Biol. 267: 727-748 (1997)); Glide (Halgren, T. A. et al., “Glide: a new approach for rapid, accurate docking and scoring. 2. Enrichment factors in database screening.” J Med Chem, 47:1750-1759 (2004), Friesner, R. A. et al., “Glide: a new approach for rapid, accurate docking and scoring. 1. Method and assessment of docking accuracy.” J Med Chem, 47:1739-1749 (2004)); FlexX (Rarey, M. et al., “A fast flexible docking method using an incremental construction algorithm.” J. Mol. Biol. 261: 470-489 (1996)); and ICM (Abagyan, R. A. and Totrov, M. M., J. Mol. Biol. 235: 983-1002 (1994)).
The use of software such as GRID, a program that determines probable interaction sites between probes with various functional group characteristics and the macromolecular surface, is used to analyze the surface sites to determine structures of similar inhibiting proteins or compounds. The GRID calculations, with suitable inhibiting groups on molecules (e.g., protonated primary amines) as the probe, are used to identify potential hotspots around accessible positions at suitable energy contour levels. The program DOCK may be used to analyze an active site or ligand binding site and suggest ligands with complementary steric properties. See also, See, also, Kellenberger, P. N et al., “Recovering the true targets of specific ligands by virtual screening of the protein data bank,” Proteins 54(4):671-80 (2004); Oldfield, T., “Applications for macromolecular map interpretation: X-AUTOFIT, X-POWERFIT, X-BUILD, X-LIGAND, and X-SOLVATE,” Methods Enzymol. 374:271-300 (2003); Richardson, J. S. et al., “New tools and data for improving structures, using all-atom contacts,” Methods Enzymol. 374: 385-412 (2003); Terwilliger, T. C., “Improving macromolecular atomic models at moderate resolution by automated iterative model building, statistical density modification and refinement,” Acta Crystallogr D Biol Crystallogr. 59(Pt 7): 1174-82 (2003); Toerger, T. C. and Sacchettini, J. C., “TEXTAL system: artificial intelligence techniques for automated protein model building,” Methods Enzymol. 374:244-70 (2003); von Grotthuss, M. et al., “Predicting protein structures accurately,” Science 304(5677):1597-9 (2004); Rajakiannan, V. et al., “The use of ACORN in solving a 39.5 kDa macromolecule with 1.9 Å resolution laboratory source data,” J Synchrotron Radiat. 11(Pt 4):358-62 (2004); Claude, J. B. et al., “CaspR: a web server for automated molecular replacement using homology modeling,” Nucleic Acids Res. 32(Web Server issue):W606-9 (2004); Suhre, K. and Sanejouand, Y. H., “ElNemo: a normal mode web server for protein movement analysis and the generation of templates for molecular replacement,” Nucleic Acids Res. 32(Web Server issue):W610-4 (2004).
Once suitable chemical entities, compounds, or agents have been selected, they can be assembled into a single ligand or compound or inhibitor or activator. Assembly may proceed by visual inspection of the relationship of the fragments to each other on the three-dimensional image. This may be followed by manual model building using software such as Quanta or Sybyl.
Useful programs to aid in connecting the individual chemical entities, compounds, or agents include but are not limited to: CAVEAT (Bartlett, P. A. et al., “CAVEAT: A Program to Facilitate the Structure-Derived Design of Biologically Active Molecules.” In Molecular Recognition in Chemical and Biological, Problems, Special Pub., Royal Chem. Soc., 78, pp. 82-196 (1989)); 3D Database systems such as MACCS-3D (MDL Information Systems, San Leandro, C A and Martin, Y. C., “3D Database Searching in Drug Design,” J. Med. Chem. 35: 2145-2154 (1992); and HOOK (available from Molecular Simulations, Burlington, Mass.).
Several methodologies for searching three-dimensional databases to test hypotheses and select compounds for screening are available. These include the program CAVEAT (Bacon et al., J. Mol. Biol. 225:849-858 (1992)). For instance, CAVEAT uses databases of cyclic compounds which can act as “spacers” to connect any number of chemical fragments already positioned in the active site. This allows one skilled in the art to quickly generate hundreds of possible ways to connect the fragments already known or suspected to be necessary for tight binding.
Instead of proceeding to build an inhibitor activator, agonist or antagonist of a peptide deformylase polypeptide in a step-wise fashion one chemical entity at a time as described above, such compounds may be designed as a whole or “de novo” using either an empty active site or optionally including some portion(s) of a known molecules. These methods include: LUDI (Bohm, H.-J., “The Computer Program LUDI: A New Method for the De Novo Design of Enzyme Inhibitors”, J. Comp. Aid. Molec. Design, 6, pp. 61-78 (1992), available from Biosym Technologies, San Diego, Calif.); LEGEND (Nishibata, Y. and A. Itai, Tetrahedron 47:8985 (1991), available from Molecular Simulations, Burlington, Mass.); and LeapFrog (available from Tripos Associates, St. Louis, Mo.).
For instance, the program LUDI can determine a list of interaction sites into which to place both hydrogen bonding and hydrophobic fragments. LUDI then uses a library of linkers to connect up to four different interaction sites into fragments. Then smaller “bridging” groups such as —CH2- and —COO— are used to connect these fragments.
Once a compound has been designed or selected by the above methods, the affinity with which that compound may bind or associate with a peptide deformylase polypeptide may be tested and optimized by computational evaluation and/or by testing biological activity after synthesizing the compound. Inhibitors or compounds may interact with the deformylase in more than one conformation that is similar in overall binding energy. In those cases, the deformation energy of binding is taken to be the difference between the energy of the free compound and the average energy of the conformations observed when the compound binds to a peptide deformylase polypeptide.
A compound designed or selected as binding or associating with a plant peptide deformylase may be further computationally optimized so that in its bound state it would preferably lack repulsive electrostatic interaction with the protein. Such non-complementary (e.g., electrostatic) interactions include repulsive charge-charge, dipole-dipole and charge-dipole interactions. Specifically, the sum of all electrostatic interactions between the inhibitor and the chimera when the inhibitor is bound, preferably make a neutral or favorable contribution to the enthalpy of binding. Weak binding compounds will also be designed by these methods so as to determine SAR.
Specific computer software is available in the art to evaluate compound deformation energy and electrostatic interaction. Examples of programs designed for such uses include: Gaussian 92, revision C (M. J. Frisch, Gaussian, Inc., Pittsburgh, Pa., COPYRGT 1992); AMBER, version 4.0 (P. A. Kollman, University of California at San Francisco, COPYRGT 1994); QUANTA/CHARMM (Molecular Simulations, Inc., Burlington, Mass. COPYRGT 1994); INSIGHT II/DISCOVER (Biosysm Technologies Inc., San Diego, Calif. COPYRGT. 1994); and DELPHI (A. Nicholls and B. Honig “A rapid finite difference algorithm, utilizing successive over-relaxation to solve the Poisson-Boltzman equation” J. Comp. Chem. 12: 435-445 (1991), M. K. Gilson and B. Honig. “Calculation of the total electrostatic energy of a macromolecular system: Solvation energies, binding energies and conformation analysis” Proteins 4: 7-18 (1988), M. K. Gilson et al., “Calculating the electrostatic potential of molecules in solution: Method and error assessment” J. Comp. Chem. 9: 327-335 (1987)). Other hardware systems and software packages will be known to those skilled in the art.
Once a compound that associates with the peptide deformylase polypeptide has been optimally selected or designed, as described above, substitutions may then be made in some of its atoms or side groups in order to improve or modify its binding properties. Generally, initial substitutions are conservative, i.e., the replacement group will have approximately the same size, shape, hydrophobicity and charge as the original group. It should, of course, be understood that components known in the art to alter conformation may be avoided. Such substituted chemical compounds may then be analyzed for efficiency of fit to a peptide deformylase polypeptide by the same computer methods described in detail, above.
Accordingly, as described above the present invention provides a computer-assisted method for obtaining structural information about a molecule or a molecular complex of unknown structure including: crystallizing the molecule or molecular complex; generating an x-ray diffraction pattern from the crystallized molecule or molecular complex; applying at least a portion of the structure coordinates set forth in Table 1 to the x-ray diffraction pattern to generate a three-dimensional electron density map of at least a portion of the molecule or molecular complex whose structure is unknown.
In another aspect, the present invention provides a computer-assisted method for homology modeling an Arabidopsis thaliana peptide deformylase homolog including: aligning the amino acid sequence of an Arabidopsis thaliana peptide deformylase homolog with the amino acid sequence of Arabidopsis thaliana peptide deformylase SEQ ID NO:1 and incorporating the sequence of the Arabidopsis thaliana peptide deformylase homolog into a model of Arabidopsis thaliana peptide deformylase derived from structure coordinates set forth in Table 1 to yield a preliminary model of the Arabidopsis thaliana peptide deformylase homolog; subjecting the preliminary model to energy minimization to yield an energy minimized model; remodeling regions of the energy minimized model where stereochemistry restraints are violated to yield a final model of the Arabidopsis thaliana peptide deformylase homolog.
Domains of peptide deformylase polypeptides retain sequence and structural conservation. Accordingly, these conserved regions can be used to model deformylase homologs. Referring to FIG. 4, conservation of the three motifs in AtDEF1 and 2 and bacterial DEFs are shown. AtDEF1- and 2-like sequences were identified with a tblastn (BLAST) search of plant EST databases, aligned around the indicated motifs, and submitted for analysis by WebLogo. For the bacterial DEF alignment, the first 100 bacterial sequences from a blastp using the SwissProt database with Q2VP16 (E. coli) as query were used for the similarity analyses. Sequence conservation is represented by WebLogo images by the overall height of the stack and relative frequency of the amino acid at the position within the sequence is represented by the height of its symbol (Crooks et al., Genome Res. 14:1188-1190; Schneider and Stephens, Nucl. Acids Res. 18:6097-6100).
Due to the nature of the sequences used for the plant DEFs, different numbers of sequences were used for each motif in the generation of FIG. 4. For motif I, there were 34, 42 and 100 sequences for 1, 2 and bacterial DEFs, respectively; whereas, there were 36, 40, and 100 for motif II and 40, 32, and 100 for motif II.
In addition, referring to FIGS. 6, 7 and 8, a phylogenetic analyses of the distribution of amino acid substitutions throughout the available collection of peptide deformylase sequences from plants compared with bacterial deformylase is provided. The results are presented as a comparison of both the number and percentage of substitutions found at any location within the sequence of peptide deformylase 1 & 2 from plants as well as E. coli. There are a number of residue changes which suggest selection pressure in the evolution of peptide deformylase specifically adapted to plants. Thus, these changes are indicative of specific sites where residue changes are likely to affect peptide deformylase activity and/or specificity without adversely affecting enzyme stability and are useful as targets for mutational changes.
Thus, the structure coordinates set forth in Table 1 can be used to aid in obtaining structural information about another crystallized molecule or molecular complex. A “molecular complex” means a protein in covalent or non-covalent association with a chemical entity or compound. The method of the invention allows determination of at least a portion of the three-dimensional structure of molecules or molecular complexes which contain one or more structural features that are similar to structural features of Arabidopsis thaliana peptide deformylase. These molecules are referred to herein as “structurally homologous” to Arabidopsis thaliana peptide deformylase. Similar structural features can include, for example, regions of amino acid identity, conserved active site or binding site motifs, and similarly arranged secondary structural elements (e.g., α helices and β sheets). Optionally, structural homology is determined by aligning the residues of the two amino acid sequences to optimize the number of identical amino acids along the lengths of their sequences; gaps in either or both sequences are permitted in making the alignment in order to optimize the number of identical amino acids, although the amino acids in each sequence must nonetheless remain in their proper order. Preferably, two amino acid sequences are compared using the Blastp program, version 2.0.9, of the BLAST 2 search algorithm, as described by Tatusova et al., FEMS Microbiol Lett., 174:247-50 (1999). Preferably, the default values for all BLAST 2 search parameters are used, including matrix=BLOSUM62; open gap penalty=11, extension gap penalty=1, gap x_dropoff=50, expect=10, wordsize=3, and filter on. In the comparison of two amino acid sequences using the BLAST search algorithm, structural similarity is referred to as “identity.” Preferably, a structurally homologous molecule is a protein that has an amino acid sequence sharing at least 65% identity with the amino acid sequence of Arabidopsis thaliana peptide deformylase. Methods for generating structural information about the structurally homologous molecule or molecular complex are well-known and include, for example, molecular replacement techniques. By using molecular replacement, all or part of the structure coordinates of Arabidopsis thaliana peptide deformylase (and set forth in Table 1) can be used to determine the structure of a crystallized molecule or molecular complex whose structure is unknown more quickly and efficiently than attempting to determine such information ab initio.
Molecular replacement provides an accurate estimation of the phases for an unknown structure. Phases are a factor in equations used to solve crystal structures that cannot be determined directly. Obtaining accurate values for the phases, by methods other than molecular replacement, is a time-consuming process that involves iterative cycles of approximations and refinements and greatly hinders the solution of crystal structures. However, when the crystal structure of a protein containing at least a structurally homologous portion has been solved, the phases from the known structure provide a satisfactory estimate of the phases for the unknown structure.
Thus, this method involves generating a preliminary model of a molecule or molecular complex whose structure coordinates are unknown, by orienting and positioning the relevant portion of Arabidopsis thaliana peptide deformylase according to Table 1 within the unit cell of the crystal of the unknown molecule or molecular complex so as best to account for the observed x-ray diffraction pattern of the crystal of the molecule or molecular complex whose structure is unknown. Phases can then be calculated from this model and combined with the observed x-ray diffraction pattern amplitudes to generate an electron density map of the structure whose coordinates are unknown. This, in turn, can be subjected to any well-known model building and structure refinement techniques to provide a final, accurate structure of the unknown crystallized molecule or molecular complex (E. Lattman, “Use of the Rotation and Translation Functions,” in Meth. Enzymol., 115:55-77 (1985); M. G. Rossman, ed., “The Molecular Replacement Method,” Int. Sci. Rev. Ser., No. 13, Gordon & Breach, New York (1972)).
Structural information about a portion of any crystallized molecule or molecular complex that is sufficiently structurally homologous to a portion of Arabidopsis thaliana peptide deformylase can be resolved by this method. In addition to a molecule that shares one or more structural features with Arabidopsis thaliana peptide deformylase as described above, a molecule that has similar bioactivity, such as the same catalytic activity, substrate specificity or ligand binding activity as Arabidopsis thaliana peptide deformylase, may also be sufficiently structurally homologous to Arabidopsis thaliana peptide deformylase to permit use of the structure coordinates of Arabidopsis thaliana peptide deformylase to solve its crystal structure.
In addition, using homology modeling, a computer model of an Arabidopsis thaliana peptide deformylase homolog can be built or refined without crystallizing the homolog. First, a preliminary model of the Arabidopsis thaliana peptide deformylase homolog is created by sequence alignment with Arabidopsis thaliana peptide deformylase, secondary structure prediction, the screening of structural libraries, or any combination of those techniques. Computational software may be used to carry out the sequence alignments and the secondary structure predictions. Structural incoherences, e.g., structural fragments around insertions and deletions, can be modeled by screening a structural library for peptides of the desired length and with a suitable conformation. For prediction of the side chain conformation, a side chain rotamer library may be employed. Where the Arabidopsis thaliana peptide deformylase homolog has been crystallized, the final homology model can be used to solve the crystal structure of the homolog by molecular replacement, as described above. Next, the preliminary model is subjected to energy minimization to yield an energy minimized model. The energy minimized model may contain regions where stereochemistry restraints are violated, in which case such regions are remodeled to obtain a final homology model. The homology model is positioned according to the results of molecular replacement, and subjected to further refinement including molecular dynamics calculations.
In another aspect, the present invention provides a computer-assisted method for designing a potential modifier of Arabidopsis thaliana peptide deformylase activity including: supplying a computer modeling application with a set of structure coordinates of a molecule or molecular complex, the molecule or molecular complex including at least a portion of at least one Arabidopsis thaliana peptide deformylase or Arabidopsis thaliana peptide deformylase-like active site, the active site including amino acids Gly121, Gly123, Leu124, Gln128, Glu169, Gly170, Cys171, Leu172, His213, Glu214, His 217, and Tyr178; supplying the computer modeling application with a set of structure coordinates for a chemical entity; evaluating the potential binding interactions between the chemical entity and active site of the molecule or molecular complex; structurally modifying the chemical entity to yield a set of structure coordinates for a modified chemical entity; and determining whether the modified chemical entity is expected to bind to the molecule or molecular complex, wherein binding to the molecule or molecular complex is indicative of potential modification of Arabidopsis thaliana peptide deformylase activity.
The present invention also provides a computer-assisted method for designing a potential modifier of Arabidopsis thaliana peptide deformylase activity de novo including: supplying a computer modeling application with a set of structure coordinates of a molecule or molecular complex, the molecule or molecular complex including at least a portion of at least one Arabidopsis thaliana peptide deformylase or Arabidopsis thaliana peptide deformylase like active site, wherein the active site includes amino acids Gly121, Gly123, Leu124, Gln128, Glu169, Gly170, Cys171, Leu172, His213, Glu214, His217, and Tyr178; forming a chemical entity represented by set of structure coordinates; and determining whether the chemical entity is expected to bind to the molecule or molecular complex, wherein binding to the molecule or molecular complex is indicative of potential modification of Arabidopsis thaliana peptide deformylase activity.
In another aspect, the present invention provides a method for making a potential modifier of Arabidopsis thaliana peptide deformylase activity, the method including chemically or enzymatically synthesizing a chemical entity to yield a potential modifier of Arabidopsis thaliana peptide deformylase activity, the chemical entity having been identified during a computer-assisted process including supplying a computer modeling application with a set of structure coordinates of a molecule or molecular complex, the molecule or molecular complex including at least a portion of a Arabidopsis thaliana peptide deformylase or Arabidopsis thaliana peptide deformylase-like active site; supplying the computer modeling application with a set of structure coordinates of a chemical entity; and determining whether the chemical entity is expected to bind to the molecule or molecular complex at the active site, wherein binding to the molecule or molecular complex is indicative of potential modification of Arabidopsis thaliana peptide deformylase activity.
In another aspect, the present invention provides a method for making a potential modifier of Arabidopsis thaliana peptide deformylase activity, the method including chemically or enzymatically synthesizing a chemical entity to yield a potential modifier of Arabidopsis thaliana peptide deformylase activity, the chemical entity having been designed during a computer-assisted process including supplying a computer modeling application with a set of structure coordinates of a molecule or molecular complex, the molecule or molecular complex including at least a portion of a Arabidopsis thaliana peptide deformylase or Arabidopsis thaliana peptide deformylase-like active site; supplying the computer modeling application with a set of structure coordinates for a chemical entity; evaluating the potential binding interactions between the chemical entity and the active site of the molecule or molecular complex; structurally modifying the chemical entity to yield a set of structure coordinates for a modified chemical entity; and determining whether the chemical entity is expected to bind to the molecule or molecular complex at the active site, wherein binding to the molecule or molecular complex is indicative of potential modification of Arabidopsis thaliana peptide deformylase activity.
In general, methods for making a potential modifier of a plant peptide deformylase activity are provided herein. Such methods include chemically or enzymatically synthesizing a chemical entity to yield a potential modifier of plant peptide deformylase activity. Those skilled in the art of crystallography will understand that the atomic coordinates provided herein can be used to design a chemical entity during a computer-assisted process that includes supplying a computer modeling application with a set of structure coordinates of a molecule or molecular complex, the molecule or molecular complex including at least a portion of a plant peptide deformylase or Arabidopsis thaliana peptide deformylase-like active site; forming a chemical entity represented by set of structure coordinates; and determining whether the chemical entity is expected to bind to the molecule or molecular complex at the active site. Binding to the molecule or molecular complex is indicative of potential modification of Arabidopsis thaliana peptide deformylase activity.
FIGS. 6-8 contain phylogenetic analyses of the distribution of amino acid substitutions throughout the available collection of peptide deformylase sequences from plants compared with bacteria. The results are presented as a comparison of both the number and percentage of substitutions found at any location within the sequence of peptide deformylase 1 & 2 from plants as well as E. coli. There are a number of residue changes which suggest selection pressure in the evolution of peptide deformylase specifically adapted to plants. Thus, these changes are indicative of specific sites where residue changes are likely to affect peptide deformylase activity and/or specificity without adversely affecting enzyme stability and are useful as targets for mutational changes.
AtDEF2 is an essential plant enzyme responsible for the co-translational processing of chloroplast translated proteins. Although biochemically characterized, no structure exists for AtDEF2 in part because of a requirement for 0.5 M NaCl for solubility. The dependency on sodium chloride for solubility was removed by limited tryptic proteolysis and crystals of AtDEF2 were obtained. The structure was determined by molecular replacement and refined to a resolution of 2.7 Å. The overall fold of the enzyme closely resembles the alpha+beta conformation of known bacterial peptide deformylases, with an r.m.s deviation of 1.04 Å on main chain atoms relative to the E. coli enzyme. The largest differences occur in the orientation of the C-terminal helix (helix 3) and the conformation of the loop between beta strands 2 and 3, which form part of the five-stranded central sheet. Modeling the preferred substrate for AtDEF2 (the N-termini of the D1 polypeptide from photosystem II), in both chloroplast protein structures can be used to elucidate the mechanism underlying the 102-fold greater activity of AtDEF2 on this sequence (see FIG. 3). Structural comparison can also be accomplished with the known eubacterial peptide deformylase structures to determine approaches for designing specific inhibitors against the chloroplast enzyme. Specific AtDEF2 inhibitors could potentially be used as broad-spectrum herbicides without impact on soil microorganisms.
The Arabidopsis thaliana DEF2 protein was over-expressed and purified from E. coli. Limited tryptic proteolysis yielded a form of Arabidopsis thaliana DEF2 (see FIG. 1B, SEQ ID NO:1) which readily crystallized. The useful crystals all belong to the tetragonal space group. The unit cell parameters were a, b, and c; wherein a is about 40 Å to about 60 Å, b is about 40 Å to about 60 Å, and c is about 120 Å to about 160 Å.
Crystals of the truncated peptide deformylase construct are grown by hanging drop vapor diffusion in 24 well plates with well solutions containing 15-18% peg monomethyl ester 550, 28-70 mM ZnSO4, and 70 mM MES pH 6.5. Protein solution at approximately 5 mg/m1 is mixed 1:1 with well solution to a final volume of 2-5 microliters for the crystallization drops. Crystals form in several days to several weeks. To prepare the crystals for data collection, they were briefly placed into a solution containing the same components as the well solution in addition to 20% glycerol, mounted in nylon or mylar loops, and flash cooled by plunging into liquid nitrogen.
Table 1 lists the atomic structure coordinates for the Arabidopsis thaliana peptide deformylase (A. thaliana DEF2) molecule as derived by x-ray diffraction from a crystal of the protein. The following abbreviations are used in Table 1. “Atom type” refers to the element whose coordinates are measured. The first letter in the column defines the element. “X, Y, Z” crystallographically define the atomic position of the element measured. “B” is a thermal factor that measures movement of the atom around its atomic center. “Occ” is an occupancy factor that refers to the fraction of the molecules in which each atom occupies the position specified by the coordinates. A value of “1” indicates that each atom has the same conformation, i.e., the same position, in all molecules of the crystal.
Table 1 is provided below:







TABLE 1





Atomic Coordinates of Crystalline Form of SEQ ID


NO: 1
















REMARK
coordinates from simulated annealing refinement


REMARK
refinement resolution: 500.0-2.4 A


REMARK
starting r = 0.2407 free_r = 0.2946


REMARK
final r = 0.2352 free_r = 0.2983


REMARK
rmsd bonds = 0.007053 rmsd angles = 1.33915


REMARK
wa_initial = 2.77981 wa_dynamics = 3.30373 wa_final = 2.90342


REMARK
target = mlf md-method = torsion annealing schedule = slowcool


REMARK
starting temperature = 2500 total md steps = 100 * 6


REMARK
sg = P4(1)2(1)2 a = 50.902 b = 50.902 c = 144.783 alpha = 90 beta = 90 gamma = 90


REMARK
parameter file 1  :  CNS_TOPPAR:protein_rep_cis.param


REMARK
parameter file 2  :  CNS_TOPPAR:ion.param


REMARK
parameter file 3  :  CNS_TOPPAR:water_rep.param


REMARK
molecular structure file: generate_r8h.mtf


REMARK
input coordinates: generate_r8h.pdb


REMARK
reflection file = pepdef1_p41212_cv.cns


REMARK
ncs = none


REMARK
B-correction resolution: 6.0-2.4


REMARK
initial B-factor correction applied to fobs:


REMARK
 B11 =  1.447 B22 =  1.447 B33 =  −2.893


REMARK
 B12 =  0.000 B13 =  0.000 B23 =   0.000


REMARK
B-factor correction applied to coordinate array B:  1.092


REMARK
bulk solvent: density level = 0.398841 e/A{circumflex over ( )}3, B-factor = 39.902 A{circumflex over ( )}2


REMARK
reflections with |Fobs|/sigma_F < 0.0 rejected


REMARK
reflections with |Fobs| > 10000 * rms(Fobs) rejected









REMARK
theoretical total number of refl. in resol. range:
8021 (100.0%)


REMARK
number of unobserved reflections (no entry or |F| = 0):
  5 (0.1%)


REMARK
number of reflections rejected:
  0 (0.0%)


REMARK
total number of reflections used:
8016 (99.9%)


REMARK
number of reflections in working set:
7166 (89.3%)


REMARK
number of reflections in test set:
 850 (10.6%)








CRYST1
 50.902  50.902  144.783  90.00  90.00  90.00 P 41 21 2


REMARK
FILENAME = “anneal_pepdef1_r8h_1.pdb”


REMARK
DATE: 28-Apr-05 13:49:32


REMARK
VERSION: 1.0


















ATOM
1
CB
ASP
A
74
39.005
−3.139
−26.015
1.00
40.08
A


ATOM
2
CG
ASP
A
74
37.793
−3.950
−25.591
1.00
39.52
A


ATOM
3
OD1
ASP
A
74
37.991
−5.048
−25.026
1.00
39.78
A


ATOM
4
OD2
ASP
A
74
36.651
−3.487
−25.804
1.00
37.24
A


ATOM
5
C
ASP
A
74
39.677
−4.292
−28.136
1.00
39.44
A


ATOM
6
O
ASP
A
74
38.789
−5.104
−28.382
1.00
40.59
A


ATOM
7
N
ASP
A
74
41.403
−3.315
−26.608
1.00
40.71
A


ATOM
8
CA
ASP
A
74
40.079
−3.996
−26.689
1.00
40.00
A


ATOM
9
N
VAL
A
75
40.329
−3.631
−29.089
1.00
36.98
A


ATOM
10
CA
VAL
A
75
40.043
−3.850
−30.503
1.00
34.57
A


ATOM
11
CB
VAL
A
75
38.952
−2.881
−31.027
1.00
35.15
A


ATOM
12
CG1
VAL
A
75
37.610
−3.228
−30.407
1.00
35.82
A


ATOM
13
CG2
VAL
A
75
39.323
−1.440
−30.706
1.00
35.83
A


ATOM
14
C
VAL
A
75
41.294
−3.686
−31.367
1.00
33.70
A


ATOM
15
O
VAL
A
75
41.849
−2.591
−31.473
1.00
31.73
A


ATOM
16
N
GLN
A
76
41.744
−4.785
−31.968
1.00
32.36
A


ATOM
17
CA
GLN
A
76
42.917
−4.752
−32.834
1.00
31.43
A


ATOM
18
CB
GLN
A
76
43.809
−5.977
−32.597
1.00
30.15
A


ATOM
19
CG
GLN
A
76
43.948
−6.377
−31.146
1.00
32.55
A


ATOM
20
CD
GLN
A
76
45.062
−7.391
−30.900
1.00
33.57
A


ATOM
21
OE1
GLN
A
76
45.222
−8.363
−31.647
1.00
30.76
A


ATOM
22
NE2
GLN
A
76
45.832
−7.169
−29.835
1.00
32.62
A


ATOM
23
C
GLN
A
76
42.442
−4.747
−34.284
1.00
30.41
A


ATOM
24
O
GLN
A
76
41.713
−5.642
−34.714
1.00
32.15
A


ATOM
25
N
PHE
A
77
42.843
−3.737
−35.042
1.00
29.07
A


ATOM
26
CA
PHE
A
77
42.442
−3.672
−36.437
1.00
29.03
A


ATOM
27
CB
PHE
A
77
41.147
−2.871
−36.582
1.00
26.50
A


ATOM
28
CG
PHE
A
77
41.287
−1.426
−36.198
1.00
25.67
A


ATOM
29
CD1
PHE
A
77
41.416
−0.442
−37.172
1.00
25.19
A


ATOM
30
CD2
PHE
A
77
41.317
−1.050
−34.858
1.00
24.82
A


ATOM
31
CE1
PHE
A
77
41.572
0.895
−36.818
1.00
23.61
A


ATOM
32
CE2
PHE
A
77
41.473
0.283
−34.497
1.00
24.11
A


ATOM
33
CZ
PHE
A
77
41.600
1.258
−35.483
1.00
23.48
A


ATOM
34
C
PHE
A
77
43.523
−3.035
−37.287
1.00
30.55
A


ATOM
35
O
PHE
A
77
44.372
−2.293
−36.789
1.00
28.47
A


ATOM
36
N
GLU
A
78
43.487
−3.355
−38.576
1.00
33.02
A


ATOM
37
CA
GLU
A
78
44.418
−2.797
−39.542
1.00
34.82
A


ATOM
38
CB
GLU
A
78
44.965
−3.876
−40.491
1.00
35.56
A


ATOM
39
CG
GLU
A
78
45.913
−4.906
−39.860
1.00
35.90
A


ATOM
40
CD
GLU
A
78
45.187
−5.934
−39.001
1.00
37.85
A


ATOM
41
OE1
GLU
A
78
44.210
−6.534
−39.493
1.00
39.60
A


ATOM
42
OE2
GLU
A
78
45.590
−6.152
−37.841
1.00
37.63
A


ATOM
43
C
GLU
A
78
43.580
−1.814
−40.339
1.00
35.67
A


ATOM
44
O
GLU
A
78
42.386
−2.030
−40.543
1.00
34.84
A


ATOM
45
N
THR
A
79
44.184
−0.713
−40.755
1.00
36.81
A


ATOM
46
CA
THR
A
79
43.448
0.241
−41.556
1.00
37.92
A


ATOM
47
CB
THR
A
79
43.983
1.662
−41.389
1.00
39.37
A


ATOM
48
OG1
THR
A
79
45.378
1.684
−41.710
1.00
42.97
A


ATOM
49
CG2
THR
A
79
43.770
2.143
−39.953
1.00
41.38
A


ATOM
50
C
THR
A
79
43.700
−0.247
−42.965
1.00
37.15
A


ATOM
51
O
THR
A
79
44.299
−1.298
−43.159
1.00
40.94
A


ATOM
52
N
CPR
A
80
43.288
0.520
−43.969
1.00
34.90
A


ATOM
53
CD
CPR
A
80
44.233
0.907
−45.032
1.00
33.68
A


ATOM
54
CA
CPR
A
80
41.941
0.367
−44.515
1.00
31.75
A


ATOM
55
CB
CPR
A
80
42.189
0.321
−46.016
1.00
32.26
A


ATOM
56
CG
CPR
A
80
43.316
1.267
−46.177
1.00
34.32
A


ATOM
57
C
CPR
A
80
41.207
−0.880
−44.023
1.00
29.73
A


ATOM
58
O
CPR
A
80
41.726
−1.994
−44.105
1.00
28.01
A


ATOM
59
N
LEU
A
81
40.000
−0.684
−43.504
1.00
26.29
A


ATOM
60
CA
LEU
A
81
39.187
−1.805
−43.067
1.00
24.35
A


ATOM
61
CB
LEU
A
81
38.007
−1.326
−42.218
1.00
20.43
A


ATOM
62
CG
LEU
A
81
38.345
−0.696
−40.868
1.00
18.48
A


ATOM
63
CD1
LEU
A
81
37.074
−0.120
−40.242
1.00
10.91
A


ATOM
64
CD2
LEU
A
81
39.000
−1.749
−39.969
1.00
15.22
A


ATOM
65
C
LEU
A
81
38.660
−2.430
−44.352
1.00
24.72
A


ATOM
66
O
LEU
A
81
38.610
−1.772
−45.392
1.00
22.96
A


ATOM
67
N
LYS
A
82
38.276
−3.698
−44.281
1.00
26.20
A


ATOM
68
CA
LYS
A
82
37.738
−4.402
−45.441
1.00
26.69
A


ATOM
69
CB
LYS
A
82
38.682
−5.540
−45.852
1.00
28.51
A


ATOM
70
CG
LYS
A
82
38.188
−6.384
−47.022
1.00
34.36
A


ATOM
71
CD
LYS
A
82
39.217
−7.445
−47.429
1.00
37.34
A


ATOM
72
CE
LYS
A
82
38.722
−8.278
−48.609
1.00
39.22
A


ATOM
73
NZ
LYS
A
82
39.762
−9.208
−49.129
1.00
41.01
A


ATOM
74
C
LYS
A
82
36.366
−4.955
−45.059
1.00
25.07
A


ATOM
75
O
LYS
A
82
36.169
−5.422
−43.940
1.00
25.23
A


ATOM
76
N
ILE
A
83
35.417
−4.896
−45.986
1.00
22.76
A


ATOM
77
CA
ILE
A
83
34.074
−5.387
−45.713
1.00
20.03
A


ATOM
78
CB
ILE
A
83
33.061
−4.820
−46.717
1.00
17.56
A


ATOM
79
CG2
ILE
A
83
31.687
−5.395
−46.443
1.00
14.23
A


ATOM
80
CG1
ILE
A
83
33.050
−3.292
−46.642
1.00
14.83
A


ATOM
81
CD1
ILE
A
83
32.504
−2.738
−45.351
1.00
18.36
A


ATOM
82
C
ILE
A
83
34.007
−6.905
−45.770
1.00
19.27
A


ATOM
83
O
ILE
A
83
34.519
−7.520
−46.697
1.00
20.95
A


ATOM
84
N
VAL
A
84
33.369
−7.498
−44.770
1.00
18.88
A


ATOM
85
CA
VAL
A
84
33.209
−8.943
−44.689
1.00
18.55
A


ATOM
86
CB
VAL
A
84
33.199
−9.409
−43.220
1.00
18.38
A


ATOM
87
CG1
VAL
A
84
32.826
−10.874
−43.136
1.00
17.47
A


ATOM
88
CG2
VAL
A
84
34.566
−9.166
−42.593
1.00
16.32
A


ATOM
89
C
VAL
A
84
31.877
−9.299
−45.343
1.00
19.91
A


ATOM
90
O
VAL
A
84
30.832
−8.759
−44.972
1.00
21.19
A


ATOM
91
N
GLU
A
85
31.912
−10.210
−46.311
1.00
19.07
A


ATOM
92
CA
GLU
A
85
30.700
−10.597
−47.022
1.00
18.15
A


ATOM
93
CB
GLU
A
85
30.957
−10.620
−48.535
1.00
19.75
A


ATOM
94
CG
GLU
A
85
31.242
−9.268
−49.179
1.00
20.83
A


ATOM
95
CD
GLU
A
85
31.658
−9.413
−50.642
1.00
24.60
A


ATOM
96
OE1
GLU
A
85
31.043
−10.251
−51.350
1.00
24.61
A


ATOM
97
OE2
GLU
A
85
32.587
−8.691
−51.086
1.00
23.72
A


ATOM
98
C
GLU
A
85
30.144
−11.948
−46.615
1.00
16.54
A


ATOM
99
O
GLU
A
85
30.891
−12.871
−46.289
1.00
15.61
A


ATOM
100
N
TYR
A
86
28.816
−12.040
−46.642
1.00
14.81
A


ATOM
101
CA
TYR
A
86
28.086
−13.273
−46.342
1.00
13.38
A


ATOM
102
CB
TYR
A
86
26.585
−13.045
−46.614
1.00
13.37
A


ATOM
103
CG
TYR
A
86
25.740
−14.294
−46.671
1.00
11.64
A


ATOM
104
CD1
TYR
A
86
25.387
−14.988
−45.508
1.00
12.48
A


ATOM
105
CE1
TYR
A
86
24.653
−16.180
−45.576
1.00
9.76
A


ATOM
106
CD2
TYR
A
86
25.330
−14.815
−47.900
1.00
10.58
A


ATOM
107
CE2
TYR
A
86
24.602
−15.993
−47.979
1.00
7.91
A


ATOM
108
CZ
TYR
A
86
24.271
−16.676
−46.821
1.00
9.19
A


ATOM
109
OH
TYR
A
86
23.624
−17.891
−46.923
1.00
9.80
A


ATOM
110
C
TYR
A
86
28.660
−14.288
−47.326
1.00
11.79
A


ATOM
111
O
TYR
A
86
29.028
−13.922
−48.443
1.00
9.00
A


ATOM
112
N
PRO
A
87
28.737
−15.571
−46.940
1.00
13.07
A


ATOM
113
CD
PRO
A
87
29.187
−16.597
−47.904
1.00
12.32
A


ATOM
114
CA
PRO
A
87
28.335
−16.193
−45.672
1.00
14.67
A


ATOM
115
CB
PRO
A
87
27.876
−17.563
−46.122
1.00
13.93
A


ATOM
116
CG
PRO
A
87
28.972
−17.908
−47.144
1.00
13.84
A


ATOM
117
C
PRO
A
87
29.449
−16.289
−44.612
1.00
16.37
A


ATOM
118
O
PRO
A
87
29.415
−17.176
−43.751
1.00
16.16
A


ATOM
119
N
ASP
A
88
30.433
−15.396
−44.676
1.00
14.88
A


ATOM
120
CA
ASP
A
88
31.529
−15.427
−43.708
1.00
16.94
A


ATOM
121
CB
ASP
A
88
32.374
−14.155
−43.811
1.00
17.27
A


ATOM
122
CG
ASP
A
88
33.647
−14.237
−42.991
1.00
20.01
A


ATOM
123
OD1
ASP
A
88
33.564
−14.530
−41.779
1.00
22.56
A


ATOM
124
OD2
ASP
A
88
34.734
−14.005
−43.559
1.00
22.48
A


ATOM
125
C
ASP
A
88
30.964
−15.563
−42.286
1.00
17.02
A


ATOM
126
O
ASP
A
88
30.111
−14.771
−41.864
1.00
14.24
A


ATOM
127
N
PRO
A
89
31.454
−16.562
−41.528
1.00
17.30
A


ATOM
128
CD
PRO
A
89
32.572
−17.414
−41.972
1.00
17.85
A


ATOM
129
CA
PRO
A
89
31.063
−16.896
−40.148
1.00
16.77
A


ATOM
130
CB
PRO
A
89
32.039
−18.014
−39.769
1.00
17.99
A


ATOM
131
CG
PRO
A
89
32.412
−18.623
−41.091
1.00
19.05
A


ATOM
132
C
PRO
A
89
31.102
−15.742
−39.141
1.00
17.05
A


ATOM
133
O
PRO
A
89
30.343
−15.737
−38.167
1.00
14.98
A


ATOM
134
N
ILE
A
90
31.997
−14.781
−39.371
1.00
16.08
A


ATOM
135
CA
ILE
A
90
32.138
−13.624
−38.489
1.00
15.58
A


ATOM
136
CB
ILE
A
90
33.228
−12.657
−39.019
1.00
14.80
A


ATOM
137
CG2
ILE
A
90
33.261
−11.394
−38.178
1.00
12.19
A


ATOM
138
CG1
ILE
A
90
34.596
−13.344
−38.983
1.00
15.77
A


ATOM
139
CD1
ILE
A
90
35.729
−12.544
−39.637
1.00
14.96
A


ATOM
140
C
ILE
A
90
30.823
−12.853
−38.332
1.00
15.25
A


ATOM
141
O
ILE
A
90
30.595
−12.190
−37.318
1.00
13.85
A


ATOM
142
N
LEU
A
91
29.951
−12.960
−39.329
1.00
13.85
A


ATOM
143
CA
LEU
A
91
28.679
−12.262
−39.295
1.00
12.86
A


ATOM
144
CB
LEU
A
91
28.124
−12.129
−40.709
1.00
8.77
A


ATOM
145
CG
LEU
A
91
29.118
−11.425
−41.639
1.00
8.91
A


ATOM
146
CD1
LEU
A
91
28.533
−11.337
−43.034
1.00
9.63
A


ATOM
147
CD2
LEU
A
91
29.460
−10.035
−41.096
1.00
7.28
A


ATOM
148
C
LEU
A
91
27.666
−12.934
−38.383
1.00
14.00
A


ATOM
149
O
LEU
A
91
26.585
−12.392
−38.147
1.00
15.75
A


ATOM
150
N
ARG
A
92
28.024
−14.102
−37.856
1.00
14.41
A


ATOM
151
CA
ARG
A
92
27.142
−14.841
−36.946
1.00
16.37
A


ATOM
152
CB
ARG
A
92
26.771
−16.202
−37.541
1.00
17.16
A


ATOM
153
CG
ARG
A
92
26.132
−16.163
−38.904
1.00
17.07
A


ATOM
154
CD
ARG
A
92
24.720
−15.650
−38.825
1.00
17.49
A


ATOM
155
NE
ARG
A
92
23.973
−15.900
−40.058
1.00
16.77
A


ATOM
156
CZ
ARG
A
92
22.704
−15.549
−40.237
1.00
15.33
A


ATOM
157
NH1
ARG
A
92
22.042
−14.928
−39.263
1.00
15.95
A


ATOM
158
NH2
ARG
A
92
22.093
−15.828
−41.378
1.00
15.85
A


ATOM
159
C
ARG
A
92
27.832
−15.099
−35.609
1.00
16.73
A


ATOM
160
O
ARG
A
92
27.185
−15.475
−34.636
1.00
16.22
A


ATOM
161
N
ALA
A
93
29.142
−14.874
−35.582
1.00
18.23
A


ATOM
162
CA
ALA
A
93
30.006
−15.132
−34.425
1.00
22.48
A


ATOM
163
CB
ALA
A
93
31.457
−14.786
−34.797
1.00
23.31
A


ATOM
164
C
ALA
A
93
29.726
−14.602
−33.015
1.00
24.67
A


ATOM
165
O
ALA
A
93
30.506
−14.902
−32.106
1.00
28.53
A


ATOM
166
N
LYS
A
94
28.665
−13.833
−32.799
1.00
24.09
A


ATOM
167
CA
LYS
A
94
28.384
−13.346
−31.439
1.00
24.96
A


ATOM
168
CB
LYS
A
94
28.436
−14.500
−30.437
1.00
25.30
A


ATOM
169
CG
LYS
A
94
28.341
−14.049
−29.000
1.00
29.01
A


ATOM
170
CD
LYS
A
94
29.295
−14.836
−28.131
1.00
32.16
A


ATOM
171
CE
LYS
A
94
29.502
−14.124
−26.805
1.00
33.93
A


ATOM
172
NZ
LYS
A
94
29.929
−12.709
−27.033
1.00
34.32
A


ATOM
173
C
LYS
A
94
29.371
−12.256
−31.016
1.00
22.46
A


ATOM
174
O
LYS
A
94
30.581
−12.475
−30.959
1.00
21.86
A


ATOM
175
N
ASN
A
95
28.832
−11.093
−30.673
1.00
21.41
A


ATOM
176
CA
ASN
A
95
29.657
−9.946
−30.341
1.00
22.01
A


ATOM
177
CB
ASN
A
95
29.187
−8.774
−31.208
1.00
20.42
A


ATOM
178
CG
ASN
A
95
28.983
−9.187
−32.651
1.00
19.92
A


ATOM
179
OD1
ASN
A
95
27.859
−9.463
−33.085
1.00
18.30
A


ATOM
180
ND2
ASN
A
95
30.081
−9.268
−33.397
1.00
20.07
A


ATOM
181
C
ASN
A
95
29.774
−9.517
−28.884
1.00
21.39
A


ATOM
182
O
ASN
A
95
28.777
−9.287
−28.199
1.00
20.41
A


ATOM
183
N
LYS
A
96
31.019
−9.395
−28.434
1.00
23.00
A


ATOM
184
CA
LYS
A
96
31.334
−8.989
−27.071
1.00
23.73
A


ATOM
185
CB
LYS
A
96
32.779
−9.351
−26.732
1.00
25.32
A


ATOM
186
CG
LYS
A
96
33.051
−10.845
−26.646
1.00
26.59
A


ATOM
187
CD
LYS
A
96
34.537
−11.110
−26.428
1.00
30.79
A


ATOM
188
CE
LYS
A
96
34.831
−12.599
−26.255
1.00
32.28
A


ATOM
189
NZ
LYS
A
96
36.296
−12.888
−26.289
1.00
32.84
A


ATOM
190
C
LYS
A
96
31.135
−7.492
−26.874
1.00
25.90
A


ATOM
191
O
LYS
A
96
31.421
−6.686
−27.769
1.00
25.26
A


ATOM
192
N
ARG
A
97
30.642
−7.134
−25.692
1.00
26.74
A


ATOM
193
CA
ARG
A
97
30.402
−5.743
−25.336
1.00
27.69
A


ATOM
194
CB
ARG
A
97
29.702
−5.662
−23.979
1.00
28.92
A


ATOM
195
CG
ARG
A
97
28.317
−6.287
−23.952
1.00
33.87
A


ATOM
196
CD
ARG
A
97
27.813
−6.493
−22.525
1.00
37.61
A


ATOM
197
NE
ARG
A
97
28.062
−5.314
−21.706
1.00
39.27
A


ATOM
198
CZ
ARG
A
97
29.170
−5.119
−20.999
1.00
40.73
A


ATOM
199
NH1
ARG
A
97
30.132
−6.035
−20.995
1.00
41.21
A


ATOM
200
NH2
ARG
A
97
29.334
−3.987
−20.330
1.00
40.81
A


ATOM
201
C
ARG
A
97
31.730
−5.009
−25.262
1.00
27.45
A


ATOM
202
O
ARG
A
97
32.773
−5.619
−25.014
1.00
27.82
A


ATOM
203
N
ILE
A
98
31.689
−3.702
−25.487
1.00
25.11
A


ATOM
204
CA
ILE
A
98
32.889
−2.888
−25.426
1.00
24.66
A


ATOM
205
CB
ILE
A
98
32.866
−1.803
−26.529
1.00
24.88
A


ATOM
206
CG2
ILE
A
98
33.965
−0.767
−26.301
1.00
20.36
A


ATOM
207
CG1
ILE
A
98
33.044
−2.485
−27.891
1.00
24.66
A


ATOM
208
CD1
ILE
A
98
33.092
−1.538
−29.061
1.00
28.24
A


ATOM
209
C
ILE
A
98
32.997
−2.267
−24.035
1.00
24.19
A


ATOM
210
O
ILE
A
98
32.093
−1.571
−23.581
1.00
24.25
A


ATOM
211
N
ASP
A
99
34.104
−2.549
−23.359
1.00
23.56
A


ATOM
212
CA
ASP
A
99
34.339
−2.053
−22.008
1.00
23.39
A


ATOM
213
CB
ASP
A
99
34.250
−3.214
−21.018
1.00
23.94
A


ATOM
214
CG
ASP
A
99
35.163
−4.366
−21.394
1.00
24.05
A


ATOM
215
OD1
ASP
A
99
35.055
−5.439
−20.766
1.00
24.51
A


ATOM
216
OD2
ASP
A
99
35.991
−4.196
−22.318
1.00
23.12
A


ATOM
217
C
ASP
A
99
35.699
−1.370
−21.880
1.00
23.34
A


ATOM
218
O
ASP
A
99
36.285
−1.317
−20.800
1.00
21.90
A


ATOM
219
N
ILE
A
100
36.204
−0.875
−23.002
1.00
22.91
A


ATOM
220
CA
ILE
A
100
37.469
−0.161
−23.033
1.00
22.92
A


ATOM
221
CB
ILE
A
100
38.647
−1.068
−23.461
1.00
21.59
A


ATOM
222
CG2
ILE
A
100
39.872
−0.209
−23.780
1.00
21.34
A


ATOM
223
CG1
ILE
A
100
38.960
−2.072
−22.342
1.00
20.46
A


ATOM
224
CD1
ILE
A
100
40.247
−2.845
−22.530
1.00
16.61
A


ATOM
225
C
ILE
A
100
37.292
0.975
−24.026
1.00
23.77
A


ATOM
226
O
ILE
A
100
37.268
0.767
−25.243
1.00
22.69
A


ATOM
227
N
PHE
A
101
37.145
2.179
−23.489
1.00
23.83
A


ATOM
228
CA
PHE
A
101
36.934
3.360
−24.308
1.00
24.41
A


ATOM
229
CB
PHE
A
101
35.788
4.175
−23.705
1.00
23.98
A


ATOM
230
CG
PHE
A
101
34.559
3.343
−23.419
1.00
24.14
A


ATOM
231
CD1
PHE
A
101
34.480
2.567
−22.261
1.00
25.77
A


ATOM
232
CD2
PHE
A
101
33.517
3.274
−24.339
1.00
23.97
A


ATOM
233
CE1
PHE
A
101
33.379
1.729
−22.025
1.00
26.25
A


ATOM
234
CE2
PHE
A
101
32.413
2.444
−24.115
1.00
24.68
A


ATOM
235
CZ
PHE
A
101
32.344
1.669
−22.958
1.00
24.94
A


ATOM
236
C
PHE
A
101
38.227
4.152
−24.398
1.00
24.03
A


ATOM
237
O
PHE
A
101
38.514
5.009
−23.565
1.00
24.43
A


ATOM
238
N
ASP
A
102
39.002
3.840
−25.435
1.00
23.26
A


ATOM
239
CA
ASP
A
102
40.301
4.458
−25.658
1.00
22.30
A


ATOM
240
CB
ASP
A
102
41.408
3.437
−25.360
1.00
22.09
A


ATOM
241
CG
ASP
A
102
41.328
2.199
−26.256
1.00
20.92
A


ATOM
242
OD1
ASP
A
102
40.445
2.141
−27.143
1.00
18.72
A


ATOM
243
OD2
ASP
A
102
42.158
1.279
−26.072
1.00
20.13
A


ATOM
244
C
ASP
A
102
40.495
4.990
−27.066
1.00
21.70
A


ATOM
245
O
ASP
A
102
39.567
5.025
−27.868
1.00
22.38
A


ATOM
246
N
GLU
A
103
41.728
5.398
−27.349
1.00
22.47
A


ATOM
247
CA
GLU
A
103
42.108
5.927
−28.653
1.00
21.29
A


ATOM
248
CB
GLU
A
103
43.610
6.188
−28.705
1.00
19.68
A


ATOM
249
CG
GLU
A
103
43.965
7.635
−28.642
1.00
21.47
A


ATOM
250
CD
GLU
A
103
43.305
8.423
−29.741
1.00
21.50
A


ATOM
251
OE1
GLU
A
103
42.668
9.445
−29.427
1.00
20.68
A


ATOM
252
OE2
GLU
A
103
43.427
8.020
−30.914
1.00
22.92
A


ATOM
253
C
GLU
A
103
41.764
4.954
−29.754
1.00
20.91
A


ATOM
254
O
GLU
A
103
41.172
5.331
−30.767
1.00
19.57
A


ATOM
255
N
ASN
A
104
42.172
3.705
−29.550
1.00
21.14
A


ATOM
256
CA
ASN
A
104
41.937
2.639
−30.507
1.00
22.17
A


ATOM
257
CB
ASN
A
104
42.341
1.299
−29.897
1.00
26.29
A


ATOM
258
CG
ASN
A
104
43.312
0.541
−30.766
1.00
29.79
A


ATOM
259
OD1
ASN
A
104
43.027
0.261
−31.930
1.00
33.45
A


ATOM
260
ND2
ASN
A
104
44.473
0.204
−30.208
1.00
30.61
A


ATOM
261
C
ASN
A
104
40.473
2.593
−30.920
1.00
22.03
A


ATOM
262
O
ASN
A
104
40.160
2.479
−32.108
1.00
21.05
A


ATOM
263
N
LEU
A
105
39.581
2.684
−29.934
1.00
19.85
A


ATOM
264
CA
LEU
A
105
38.150
2.657
−30.199
1.00
19.86
A


ATOM
265
CB
LEU
A
105
37.358
2.735
−28.886
1.00
21.38
A


ATOM
266
CG
LEU
A
105
35.919
2.188
−28.821
1.00
21.48
A


ATOM
267
CD1
LEU
A
105
35.056
3.165
−28.032
1.00
21.52
A


ATOM
268
CD2
LEU
A
105
35.341
1.980
−30.207
1.00
21.83
A


ATOM
269
C
LEU
A
105
37.771
3.830
−31.102
1.00
19.11
A


ATOM
270
O
LEU
A
105
36.987
3.668
−32.036
1.00
19.29
A


ATOM
271
N
LYS
A
106
38.328
5.008
−30.820
1.00
17.86
A


ATOM
272
CA
LYS
A
106
38.051
6.194
−31.627
1.00
18.70
A


ATOM
273
CB
LYS
A
106
38.639
7.449
−30.974
1.00
18.90
A


ATOM
274
CG
LYS
A
106
38.329
8.737
−31.744
1.00
21.08
A


ATOM
275
CD
LYS
A
106
38.916
9.962
−31.051
1.00
20.57
A


ATOM
276
CE
LYS
A
106
40.425
10.037
−31.200
1.00
19.98
A


ATOM
277
NZ
LYS
A
106
41.013
11.166
−30.404
1.00
18.10
A


ATOM
278
C
LYS
A
106
38.597
6.061
−33.058
1.00
18.80
A


ATOM
279
O
LYS
A
106
37.914
6.413
−34.023
1.00
18.37
A


ATOM
280
N
ASN
A
107
39.822
5.556
−33.190
1.00
17.20
A


ATOM
281
CA
ASN
A
107
40.431
5.370
−34.506
1.00
18.47
A


ATOM
282
CB
ASN
A
107
41.857
4.814
−34.363
1.00
21.05
A


ATOM
283
CG
ASN
A
107
42.777
5.725
−33.544
1.00
24.77
A


ATOM
284
OD1
ASN
A
107
43.803
5.275
−33.021
1.00
26.42
A


ATOM
285
ND2
ASN
A
107
42.423
7.005
−33.441
1.00
23.25
A


ATOM
286
C
ASN
A
107
39.587
4.394
−35.332
1.00
17.56
A


ATOM
287
O
ASN
A
107
39.453
4.543
−36.545
1.00
17.37
A


ATOM
288
N
LEU
A
108
39.008
3.401
−34.659
1.00
18.87
A


ATOM
289
CA
LEU
A
108
38.182
2.393
−35.315
1.00
18.66
A


ATOM
290
CB
LEU
A
108
37.754
1.318
−34.310
1.00
17.82
A


ATOM
291
CG
LEU
A
108
37.452
−0.094
−34.834
1.00
18.20
A


ATOM
292
CD1
LEU
A
108
36.611
−0.846
−33.809
1.00
14.71
A


ATOM
293
CD2
LEU
A
108
36.712
−0.033
−36.137
1.00
16.41
A


ATOM
294
C
LEU
A
108
36.938
3.025
−35.936
1.00
19.55
A


ATOM
295
O
LEU
A
108
36.669
2.851
−37.127
1.00
20.36
A


ATOM
296
N
VAL
A
109
36.183
3.752
−35.117
1.00
19.78
A


ATOM
297
CA
VAL
A
109
34.961
4.412
−35.567
1.00
20.39
A


ATOM
298
CB
VAL
A
109
34.391
5.350
−34.460
1.00
20.97
A


ATOM
299
CG1
VAL
A
109
33.245
6.201
−35.014
1.00
18.35
A


ATOM
300
CG2
VAL
A
109
33.908
4.514
−33.282
1.00
18.10
A


ATOM
301
C
VAL
A
109
35.207
5.218
−36.841
1.00
21.06
A


ATOM
302
O
VAL
A
109
34.448
5.104
−37.815
1.00
20.21
A


ATOM
303
N
ASP
A
110
36.268
6.021
−36.833
1.00
19.90
A


ATOM
304
CA
ASP
A
110
36.609
6.834
−37.993
1.00
19.28
A


ATOM
305
CB
ASP
A
110
37.787
7.760
−37.665
1.00
21.34
A


ATOM
306
CG
ASP
A
110
38.385
8.412
−38.904
1.00
23.52
A


ATOM
307
OD1
ASP
A
110
39.280
7.805
−39.525
1.00
23.06
A


ATOM
308
OD2
ASP
A
110
37.950
9.526
−39.264
1.00
25.77
A


ATOM
309
C
ASP
A
110
36.954
5.948
−39.187
1.00
18.12
A


ATOM
310
O
ASP
A
110
36.606
6.260
−40.326
1.00
16.99
A


ATOM
311
N
ALA
A
111
37.640
4.842
−38.928
1.00
17.77
A


ATOM
312
CA
ALA
A
111
38.007
3.934
−40.014
1.00
18.12
A


ATOM
313
CB
ALA
A
111
38.991
2.879
−39.517
1.00
17.41
A


ATOM
314
C
ALA
A
111
36.747
3.265
−40.559
1.00
18.06
A


ATOM
315
O
ALA
A
111
36.688
2.909
−41.735
1.00
17.71
A


ATOM
316
N
MET
A
112
35.741
3.093
−39.700
1.00
16.57
A


ATOM
317
CA
MET
A
112
34.493
2.476
−40.131
1.00
16.68
A


ATOM
318
CB
MET
A
112
33.625
2.094
−38.932
1.00
16.96
A


ATOM
319
CG
MET
A
112
34.095
0.844
−38.224
1.00
15.01
A


ATOM
320
SD
MET
A
112
33.117
0.488
−36.768
1.00
19.27
A


ATOM
321
CE
MET
A
112
31.718
−0.406
−37.514
1.00
17.01
A


ATOM
322
C
MET
A
112
33.729
3.421
−41.036
1.00
16.16
A


ATOM
323
O
MET
A
112
33.206
3.009
−42.072
1.00
16.11
A


ATOM
324
N
PHE
A
113
33.661
4.688
−40.643
1.00
16.28
A


ATOM
325
CA
PHE
A
113
32.965
5.674
−41.458
1.00
18.18
A


ATOM
326
CB
PHE
A
113
32.955
7.054
−40.770
1.00
16.66
A


ATOM
327
CG
PHE
A
113
31.803
7.259
−39.806
1.00
14.71
A


ATOM
328
CD1
PHE
A
113
30.482
7.154
−40.239
1.00
14.21
A


ATOM
329
CD2
PHE
A
113
32.041
7.552
−38.457
1.00
15.65
A


ATOM
330
CE1
PHE
A
113
29.406
7.334
−39.341
1.00
12.91
A


ATOM
331
CE2
PHE
A
113
30.979
7.735
−37.554
1.00
13.65
A


ATOM
332
CZ
PHE
A
113
29.658
7.624
−38.001
1.00
13.65
A


ATOM
333
C
PHE
A
113
33.674
5.763
−42.813
1.00
19.19
A


ATOM
334
O
PHE
A
113
33.036
5.966
−43.848
1.00
20.51
A


ATOM
335
N
ASP
A
114
34.993
5.593
−42.809
1.00
19.06
A


ATOM
336
CA
ASP
A
114
35.752
5.671
−44.050
1.00
19.17
A


ATOM
337
CB
ASP
A
114
37.258
5.516
−43.800
1.00
19.27
A


ATOM
338
CG
ASP
A
114
37.847
6.649
−42.972
1.00
18.16
A


ATOM
339
OD1
ASP
A
114
37.388
7.798
−43.112
1.00
18.34
A


ATOM
340
OD2
ASP
A
114
38.792
6.383
−42.194
1.00
16.95
A


ATOM
341
C
ASP
A
114
35.328
4.601
−45.047
1.00
20.74
A


ATOM
342
O
ASP
A
114
34.948
4.905
−46.178
1.00
22.18
A


ATOM
343
N
VAL
A
115
35.402
3.343
−44.635
1.00
19.76
A


ATOM
344
CA
VAL
A
115
35.051
2.271
−45.541
1.00
20.05
A


ATOM
345
CB
VAL
A
115
35.421
0.882
−44.952
1.00
18.79
A


ATOM
346
CG1
VAL
A
115
34.508
0.535
−43.781
1.00
19.87
A


ATOM
347
CG2
VAL
A
115
35.348
−0.179
−46.047
1.00
18.66
A


ATOM
348
C
VAL
A
115
33.570
2.319
−45.888
1.00
20.92
A


ATOM
349
O
VAL
A
115
33.172
1.900
−46.976
1.00
21.72
A


ATOM
350
N
MET
A
116
32.756
2.843
−44.975
1.00
20.52
A


ATOM
351
CA
MET
A
116
31.324
2.928
−45.225
1.00
20.64
A


ATOM
352
CB
MET
A
116
30.574
3.419
−43.975
1.00
21.83
A


ATOM
353
CG
MET
A
116
29.047
3.419
−44.133
1.00
21.70
A


ATOM
354
SD
MET
A
116
28.146
4.174
−42.758
1.00
25.32
A


ATOM
355
CE
MET
A
116
28.020
5.885
−43.298
1.00
22.79
A


ATOM
356
C
MET
A
116
31.107
3.896
−46.387
1.00
21.10
A


ATOM
357
O
MET
A
116
30.475
3.544
−47.389
1.00
18.06
A


ATOM
358
N
TYR
A
117
31.652
5.106
−46.247
1.00
21.03
A


ATOM
359
CA
TYR
A
117
31.537
6.135
−47.275
1.00
20.92
A


ATOM
360
CB
TYR
A
117
32.175
7.448
−46.809
1.00
20.51
A


ATOM
361
CG
TYR
A
117
31.419
8.154
−45.709
1.00
18.43
A


ATOM
362
CD1
TYR
A
117
30.033
8.240
−45.744
1.00
17.94
A


ATOM
363
CE1
TYR
A
117
29.328
8.917
−44.754
1.00
18.18
A


ATOM
364
CD2
TYR
A
117
32.089
8.765
−44.652
1.00
17.61
A


ATOM
365
CE2
TYR
A
117
31.391
9.450
−43.655
1.00
17.47
A


ATOM
366
CZ
TYR
A
117
30.011
9.518
−43.719
1.00
16.23
A


ATOM
367
OH
TYR
A
117
29.301
10.186
−42.759
1.00
18.52
A


ATOM
368
C
TYR
A
117
32.212
5.700
−48.563
1.00
22.73
A


ATOM
369
O
TYR
A
117
31.717
5.976
−49.653
1.00
22.10
A


ATOM
370
N
LYS
A
118
33.356
5.034
−48.434
1.00
24.25
A


ATOM
371
CA
LYS
A
118
34.091
4.576
−49.602
1.00
25.84
A


ATOM
372
CB
LYS
A
118
35.328
3.776
−49.188
1.00
26.26
A


ATOM
373
CG
LYS
A
118
36.230
3.407
−50.364
1.00
30.30
A


ATOM
374
CD
LYS
A
118
37.218
2.273
−50.035
1.00
31.07
A


ATOM
375
CE
LYS
A
118
36.496
0.934
−49.841
1.00
32.32
A


ATOM
376
NZ
LYS
A
118
37.410
−0.253
−49.726
1.00
29.48
A


ATOM
377
C
LYS
A
118
33.189
3.687
−50.446
1.00
27.75
A


ATOM
378
O
LYS
A
118
33.102
3.836
−51.667
1.00
27.33
A


ATOM
379
N
THR
A
119
32.510
2.765
−49.774
1.00
28.14
A


ATOM
380
CA
THR
A
119
31.637
1.814
−50.438
1.00
28.42
A


ATOM
381
CB
THR
A
119
31.617
0.480
−49.649
1.00
28.33
A


ATOM
382
OG1
THR
A
119
31.330
0.739
−48.269
1.00
29.06
A


ATOM
383
CG2
THR
A
119
32.975
−0.211
−49.738
1.00
27.56
A


ATOM
384
C
THR
A
119
30.223
2.354
−50.631
1.00
29.80
A


ATOM
385
O
THR
A
119
29.297
1.607
−50.955
1.00
28.97
A


ATOM
386
N
ASP
A
120
30.078
3.665
−50.454
1.00
31.38
A


ATOM
387
CA
ASP
A
120
28.790
4.333
−50.605
1.00
32.18
A


ATOM
388
CB
ASP
A
120
28.401
4.406
−52.092
1.00
34.50
A


ATOM
389
CG
ASP
A
120
29.104
5.544
−52.828
1.00
38.27
A


ATOM
390
OD1
ASP
A
120
28.855
6.724
−52.478
1.00
40.42
A


ATOM
391
OD2
ASP
A
120
29.905
5.266
−53.752
1.00
38.92
A


ATOM
392
C
ASP
A
120
27.724
3.599
−49.800
1.00
30.66
A


ATOM
393
O
ASP
A
120
26.683
3.199
−50.323
1.00
31.17
A


ATOM
394
N
GLY
A
121
28.012
3.415
−48.517
1.00
28.44
A


ATOM
395
CA
GLY
A
121
27.087
2.734
−47.634
1.00
26.11
A


ATOM
396
C
GLY
A
121
26.363
3.735
−46.755
1.00
25.00
A


ATOM
397
O
GLY
A
121
26.607
4.944
−46.837
1.00
22.88
A


ATOM
398
N
ILE
A
122
25.484
3.240
−45.894
1.00
23.50
A


ATOM
399
CA
ILE
A
122
24.730
4.131
−45.032
1.00
23.79
A


ATOM
400
CB
ILE
A
122
23.255
4.131
−45.452
1.00
24.10
A


ATOM
401
CG2
ILE
A
122
22.460
3.154
−44.612
1.00
23.83
A


ATOM
402
CG1
ILE
A
122
22.721
5.555
−45.390
1.00
23.51
A


ATOM
403
CD1
ILE
A
122
23.404
6.457
−46.381
1.00
22.10
A


ATOM
404
C
ILE
A
122
24.852
3.766
−43.568
1.00
22.35
A


ATOM
405
O
ILE
A
122
24.598
4.585
−42.685
1.00
21.65
A


ATOM
406
N
GLY
A
123
25.240
2.521
−43.329
1.00
21.64
A


ATOM
407
CA
GLY
A
123
25.405
2.018
−41.980
1.00
20.23
A


ATOM
408
C
GLY
A
123
26.421
0.892
−41.999
1.00
20.31
A


ATOM
409
O
GLY
A
123
26.645
0.250
−43.032
1.00
21.53
A


ATOM
410
N
LEU
A
124
27.051
0.647
−40.860
1.00
19.19
A


ATOM
411
CA
LEU
A
124
28.049
−0.405
−40.784
1.00
18.26
A


ATOM
412
CB
LEU
A
124
29.366
0.095
−41.390
1.00
16.37
A


ATOM
413
CG
LEU
A
124
30.540
−0.878
−41.504
1.00
18.75
A


ATOM
414
CD1
LEU
A
124
30.236
−1.928
−42.573
1.00
20.38
A


ATOM
415
CD2
LEU
A
124
31.803
−0.101
−41.868
1.00
17.41
A


ATOM
416
C
LEU
A
124
28.264
−0.824
−39.336
1.00
17.38
A


ATOM
417
O
LEU
A
124
28.340
0.014
−38.440
1.00
17.30
A


ATOM
418
N
SER
A
125
28.352
−2.128
−39.113
1.00
16.59
A


ATOM
419
CA
SER
A
125
28.578
−2.656
−37.782
1.00
15.38
A


ATOM
420
CB
SER
A
125
27.498
−3.672
−37.429
1.00
15.89
A


ATOM
421
OG
SER
A
125
27.537
−4.772
−38.323
1.00
20.69
A


ATOM
422
C
SER
A
125
29.949
−3.324
−37.790
1.00
14.95
A


ATOM
423
O
SER
A
125
30.388
−3.824
−38.819
1.00
13.32
A


ATOM
424
N
ALA
A
126
30.616
−3.319
−36.641
1.00
13.72
A


ATOM
425
CA
ALA
A
126
31.942
−3.903
−36.498
1.00
14.24
A


ATOM
426
CB
ALA
A
126
32.362
−3.878
−35.034
1.00
13.11
A


ATOM
427
C
ALA
A
126
32.089
−5.318
−37.060
1.00
14.55
A


ATOM
428
O
ALA
A
126
33.113
−5.640
−37.663
1.00
16.65
A


ATOM
429
N
PRO
A
127
31.083
−6.188
−36.859
1.00
15.05
A


ATOM
430
CD
PRO
A
127
29.881
−6.062
−36.012
1.00
13.21
A


ATOM
431
CA
PRO
A
127
31.205
−7.549
−37.395
1.00
14.59
A


ATOM
432
CB
PRO
A
127
29.837
−8.155
−37.104
1.00
15.34
A


ATOM
433
CG
PRO
A
127
29.489
−7.513
−35.782
1.00
14.66
A


ATOM
434
C
PRO
A
127
31.522
−7.518
−38.885
1.00
15.75
A


ATOM
435
O
PRO
A
127
32.242
−8.382
−39.400
1.00
12.00
A


ATOM
436
N
GLN
A
128
30.993
−6.498
−39.559
1.00
15.65
A


ATOM
437
CA
GLN
A
128
31.191
−6.323
−40.993
1.00
17.40
A


ATOM
438
CB
GLN
A
128
30.180
−5.316
−41.542
1.00
16.39
A


ATOM
439
CG
GLN
A
128
28.812
−5.917
−41.778
1.00
18.40
A


ATOM
440
CD
GLN
A
128
27.801
−4.891
−42.228
1.00
20.84
A


ATOM
441
OE1
GLN
A
128
27.428
−4.002
−41.458
1.00
22.13
A


ATOM
442
NE2
GLN
A
128
27.350
−4.999
−43.482
1.00
18.66
A


ATOM
443
C
GLN
A
128
32.603
−5.912
−41.396
1.00
19.05
A


ATOM
444
O
GLN
A
128
32.919
−5.860
−42.584
1.00
20.10
A


ATOM
445
N
VAL
A
129
33.448
−5.608
−40.418
1.00
19.63
A


ATOM
446
CA
VAL
A
129
34.828
−5.241
−40.712
1.00
20.04
A


ATOM
447
CB
VAL
A
129
35.152
−3.775
−40.284
1.00
20.18
A


ATOM
448
CG1
VAL
A
129
34.404
−2.805
−41.161
1.00
18.05
A


ATOM
449
CG2
VAL
A
129
34.780
−3.546
−38.829
1.00
19.45
A


ATOM
450
C
VAL
A
129
35.773
−6.216
−40.002
1.00
21.14
A


ATOM
451
O
VAL
A
129
36.959
−5.944
−39.844
1.00
21.90
A


ATOM
452
N
GLY
A
130
35.228
−7.348
−39.561
1.00
22.19
A


ATOM
453
CA
GLY
A
130
36.035
−8.368
−38.907
1.00
20.21
A


ATOM
454
C
GLY
A
130
36.113
−8.351
−37.390
1.00
19.73
A


ATOM
455
O
GLY
A
130
36.776
−9.201
−36.790
1.00
18.88
A


ATOM
456
N
LEU
A
131
35.445
−7.396
−36.758
1.00
17.97
A


ATOM
457
CA
LEU
A
131
35.488
−7.307
−35.305
1.00
16.71
A


ATOM
458
CB
LEU
A
131
35.860
−5.890
−34.878
1.00
17.61
A


ATOM
459
CG
LEU
A
131
37.335
−5.519
−35.060
1.00
19.78
A


ATOM
460
CD1
LEU
A
131
37.765
−5.704
−36.509
1.00
21.35
A


ATOM
461
CD2
LEU
A
131
37.539
−4.091
−34.629
1.00
17.99
A


ATOM
462
C
LEU
A
131
34.175
−7.717
−34.662
1.00
16.20
A


ATOM
463
O
LEU
A
131
33.110
−7.171
−34.979
1.00
16.20
A


ATOM
464
N
ASN
A
132
34.249
−8.687
−33.758
1.00
15.11
A


ATOM
465
CA
ASN
A
132
33.049
−9.158
−33.092
1.00
14.07
A


ATOM
466
CB
ASN
A
132
33.109
−10.675
−32.904
1.00
14.53
A


ATOM
467
CG
ASN
A
132
32.921
−11.420
−34.221
1.00
15.08
A


ATOM
468
OD1
ASN
A
132
33.885
−11.786
−34.882
1.00
17.92
A


ATOM
469
ND2
ASN
A
132
31.673
−11.611
−34.617
1.00
13.68
A


ATOM
470
C
ASN
A
132
32.768
−8.444
−31.780
1.00
13.50
A


ATOM
471
O
ASN
A
132
32.749
−9.050
−30.708
1.00
13.65
A


ATOM
472
N
VAL
A
133
32.549
−7.138
−31.890
1.00
12.59
A


ATOM
473
CA
VAL
A
133
32.242
−6.307
−30.741
1.00
13.93
A


ATOM
474
CB
VAL
A
133
33.409
−5.347
−30.416
1.00
10.85
A


ATOM
475
CG1
VAL
A
133
34.607
−6.149
−29.931
1.00
10.23
A


ATOM
476
CG2
VAL
A
133
33.784
−4.544
−31.638
1.00
10.25
A


ATOM
477
C
VAL
A
133
30.971
−5.513
−31.018
1.00
13.57
A


ATOM
478
O
VAL
A
133
30.563
−5.364
−32.162
1.00
13.60
A


ATOM
479
N
GLN
A
134
30.353
−5.002
−29.963
1.00
15.90
A


ATOM
480
CA
GLN
A
134
29.111
−4.246
−30.100
1.00
17.13
A


ATOM
481
CB
GLN
A
134
28.276
−4.439
−28.831
1.00
15.99
A


ATOM
482
CG
GLN
A
134
27.851
−5.906
−28.679
1.00
17.43
A


ATOM
483
CD
GLN
A
134
27.161
−6.217
−27.368
1.00
19.77
A


ATOM
484
OE1
GLN
A
134
26.439
−5.386
−26.822
1.00
23.84
A


ATOM
485
NE2
GLN
A
134
27.359
−7.433
−26.866
1.00
18.29
A


ATOM
486
C
GLN
A
134
29.324
−2.771
−30.423
1.00
16.76
A


ATOM
487
O
GLN
A
134
29.182
−1.900
−29.566
1.00
16.52
A


ATOM
488
N
LEU
A
135
29.672
−2.515
−31.682
1.00
15.24
A


ATOM
489
CA
LEU
A
135
29.928
−1.162
−32.172
1.00
15.82
A


ATOM
490
CB
LEU
A
135
31.436
−0.933
−32.344
1.00
14.00
A


ATOM
491
CG
LEU
A
135
31.828
0.460
−32.840
1.00
15.40
A


ATOM
492
CD1
LEU
A
135
31.450
1.490
−31.775
1.00
14.23
A


ATOM
493
CD2
LEU
A
135
33.322
0.508
−33.163
1.00
12.52
A


ATOM
494
C
LEU
A
135
29.218
−0.931
−33.502
1.00
14.99
A


ATOM
495
O
LEU
A
135
29.251
−1.773
−34.400
1.00
15.49
A


ATOM
496
N
MET
A
136
28.608
0.235
−33.638
1.00
16.04
A


ATOM
497
CA
MET
A
136
27.859
0.561
−34.841
1.00
18.35
A


ATOM
498
CB
MET
A
136
26.396
0.180
−34.588
1.00
19.43
A


ATOM
499
CG
MET
A
136
25.375
0.880
−35.438
1.00
23.19
A


ATOM
500
SD
MET
A
136
23.777
0.872
−34.619
1.00
26.18
A


ATOM
501
CE
MET
A
136
23.640
−0.872
−34.190
1.00
22.49
A


ATOM
502
C
MET
A
136
27.967
2.039
−35.255
1.00
19.14
A


ATOM
503
O
MET
A
136
28.119
2.934
−34.408
1.00
18.03
A


ATOM
504
N
VAL
A
137
27.904
2.284
−36.563
1.00
18.64
A


ATOM
505
CA
VAL
A
137
27.941
3.643
−37.094
1.00
19.57
A


ATOM
506
CB
VAL
A
137
29.354
4.075
−37.558
1.00
21.08
A


ATOM
507
CG1
VAL
A
137
30.374
3.826
−36.451
1.00
20.89
A


ATOM
508
CG2
VAL
A
137
29.723
3.356
−38.854
1.00
20.49
A


ATOM
509
C
VAL
A
137
27.018
3.757
−38.301
1.00
20.02
A


ATOM
510
O
VAL
A
137
26.667
2.754
−38.933
1.00
18.78
A


ATOM
511
N
PHE
A
138
26.621
4.985
−38.614
1.00
20.79
A


ATOM
512
CA
PHE
A
138
25.771
5.225
−39.762
1.00
22.08
A


ATOM
513
CB
PHE
A
138
24.451
4.446
−39.629
1.00
23.84
A


ATOM
514
CG
PHE
A
138
23.535
4.947
−38.549
1.00
22.93
A


ATOM
515
CD1
PHE
A
138
22.588
5.926
−38.822
1.00
25.45
A


ATOM
516
CD2
PHE
A
138
23.584
4.405
−37.268
1.00
25.82
A


ATOM
517
CE1
PHE
A
138
21.692
6.357
−37.832
1.00
24.76
A


ATOM
518
CE2
PHE
A
138
22.697
4.829
−36.271
1.00
25.19
A


ATOM
519
CZ
PHE
A
138
21.748
5.807
−36.558
1.00
24.73
A


ATOM
520
C
PHE
A
138
25.511
6.705
−39.982
1.00
23.31
A


ATOM
521
O
PHE
A
138
25.671
7.530
−39.071
1.00
21.01
A


ATOM
522
N
ASN
A
139
25.137
7.026
−41.216
1.00
24.83
A


ATOM
523
CA
ASN
A
139
24.838
8.388
−41.622
1.00
26.78
A


ATOM
524
CB
ASN
A
139
26.104
9.080
−42.113
1.00
28.84
A


ATOM
525
CG
ASN
A
139
25.919
10.574
−42.268
1.00
31.35
A


ATOM
526
OD1
ASN
A
139
24.951
11.031
−42.876
1.00
29.99
A


ATOM
527
ND2
ASN
A
139
26.850
11.346
−41.717
1.00
31.87
A


ATOM
528
C
ASN
A
139
23.826
8.305
−42.762
1.00
27.67
A


ATOM
529
O
ASN
A
139
24.147
7.834
−43.850
1.00
26.38
A


ATOM
530
N
PRO
A
140
22.587
8.762
−42.522
1.00
28.57
A


ATOM
531
CD
PRO
A
140
22.108
9.409
−41.288
1.00
27.09
A


ATOM
532
CA
PRO
A
140
21.525
8.733
−43.531
1.00
29.40
A


ATOM
533
CB
PRO
A
140
20.451
9.626
−42.923
1.00
27.26
A


ATOM
534
CG
PRO
A
140
20.606
9.366
−41.472
1.00
28.54
A


ATOM
535
C
PRO
A
140
21.976
9.231
−44.892
1.00
29.84
A


ATOM
536
O
PRO
A
140
21.655
8.635
−45.914
1.00
30.11
A


ATOM
537
N
ALA
A
141
22.716
10.332
−44.897
1.00
31.08
A


ATOM
538
CA
ALA
A
141
23.200
10.921
−46.138
1.00
33.10
A


ATOM
539
CB
ALA
A
141
23.945
12.207
−45.838
1.00
32.04
A


ATOM
540
C
ALA
A
141
24.095
9.969
−46.928
1.00
34.75
A


ATOM
541
O
ALA
A
141
23.899
9.777
−48.129
1.00
34.87
A


ATOM
542
N
GLY
A
142
25.079
9.380
−46.253
1.00
36.61
A


ATOM
543
CA
GLY
A
142
25.989
8.461
−46.916
1.00
38.38
A


ATOM
544
C
GLY
A
142
27.181
9.178
−47.519
1.00
39.97
A


ATOM
545
O
GLY
A
142
28.022
8.559
−48.175
1.00
40.45
A


ATOM
546
N
GLU
A
143
27.248
10.487
−47.293
1.00
41.61
A


ATOM
547
CA
GLU
A
143
28.327
11.321
−47.808
1.00
43.02
A


ATOM
548
CB
GLU
A
143
27.765
12.402
−48.737
1.00
44.16
A


ATOM
549
CG
GLU
A
143
26.697
11.917
−49.707
1.00
47.41
A


ATOM
550
CD
GLU
A
143
27.262
11.131
−50.874
1.00
49.37
A


ATOM
551
OE1
GLU
A
143
28.046
10.183
−50.645
1.00
50.56
A


ATOM
552
OE2
GLU
A
143
26.914
11.463
−52.027
1.00
51.60
A


ATOM
553
C
GLU
A
143
29.014
12.000
−46.630
1.00
43.65
A


ATOM
554
O
GLU
A
143
28.353
12.483
−45.710
1.00
42.94
A


ATOM
555
N
PRO
A
144
30.351
12.046
−46.639
1.00
44.50
A


ATOM
556
CD
PRO
A
144
31.298
11.494
−47.620
1.00
44.64
A


ATOM
557
CA
PRO
A
144
31.062
12.690
−45.535
1.00
45.86
A


ATOM
558
CB
PRO
A
144
32.525
12.567
−45.947
1.00
44.41
A


ATOM
559
CG
PRO
A
144
32.539
11.336
−46.788
1.00
44.69
A


ATOM
560
C
PRO
A
144
30.624
14.146
−45.431
1.00
47.73
A


ATOM
561
O
PRO
A
144
30.269
14.765
−46.437
1.00
49.56
A


ATOM
562
N
GLY
A
145
30.639
14.684
−44.216
1.00
48.72
A


ATOM
563
CA
GLY
A
145
30.260
16.070
−44.010
1.00
50.25
A


ATOM
564
C
GLY
A
145
29.010
16.538
−44.735
1.00
51.98
A


ATOM
565
O
GLY
A
145
28.889
17.719
−45.063
1.00
51.37
A


ATOM
566
N
GLU
A
146
28.074
15.625
−44.986
1.00
53.56
A


ATOM
567
CA
GLU
A
146
26.834
15.989
−45.664
1.00
54.37
A


ATOM
568
CB
GLU
A
146
26.947
15.734
−47.175
1.00
56.97
A


ATOM
569
CG
GLU
A
146
25.797
16.333
−47.990
1.00
61.12
A


ATOM
570
CD
GLU
A
146
25.915
16.063
−49.483
1.00
64.36
A


ATOM
571
OE1
GLU
A
146
25.957
14.876
−49.877
1.00
65.64
A


ATOM
572
OE2
GLU
A
146
25.961
17.040
−50.263
1.00
66.22
A


ATOM
573
C
GLU
A
146
25.640
15.224
−45.099
1.00
52.66
A


ATOM
574
O
GLU
A
146
24.731
14.850
−45.833
1.00
53.40
A


ATOM
575
N
GLY
A
147
25.646
14.994
−43.790
1.00
51.08
A


ATOM
576
CA
GLY
A
147
24.546
14.281
−43.167
1.00
48.20
A


ATOM
577
C
GLY
A
147
24.567
14.368
−41.652
1.00
46.60
A


ATOM
578
O
GLY
A
147
24.767
15.442
−41.080
1.00
46.48
A


ATOM
579
N
LYS
A
148
24.361
13.230
−40.997
1.00
44.44
A


ATOM
580
CA
LYS
A
148
24.353
13.171
−39.541
1.00
42.17
A


ATOM
581
CB
LYS
A
148
22.908
13.167
−39.032
1.00
44.06
A


ATOM
582
CG
LYS
A
148
22.653
13.989
−37.773
1.00
44.66
A


ATOM
583
CD
LYS
A
148
23.184
13.323
−36.515
1.00
46.34
A


ATOM
584
CE
LYS
A
148
22.674
14.052
−35.271
1.00
47.35
A


ATOM
585
NZ
LYS
A
148
23.051
13.382
−33.995
1.00
48.38
A


ATOM
586
C
LYS
A
148
25.064
11.889
−39.126
1.00
40.11
A


ATOM
587
O
LYS
A
148
24.509
10.799
−39.251
1.00
39.43
A


ATOM
588
N
GLU
A
149
26.297
12.020
−38.646
1.00
37.37
A


ATOM
589
CA
GLU
A
149
27.062
10.853
−38.227
1.00
35.24
A


ATOM
590
CB
GLU
A
149
28.559
11.133
−38.288
1.00
33.46
A


ATOM
591
CG
GLU
A
149
29.049
11.512
−39.662
1.00
33.59
A


ATOM
592
CD
GLU
A
149
30.535
11.306
−39.810
1.00
32.30
A


ATOM
593
OE1
GLU
A
149
31.252
11.517
−38.809
1.00
29.90
A


ATOM
594
OE2
GLU
A
149
30.982
10.943
−40.923
1.00
31.18
A


ATOM
595
C
GLU
A
149
26.692
10.414
−36.823
1.00
33.65
A


ATOM
596
O
GLU
A
149
26.843
11.169
−35.863
1.00
33.30
A


ATOM
597
N
ILE
A
150
26.210
9.180
−36.715
1.00
31.34
A


ATOM
598
CA
ILE
A
150
25.808
8.622
−35.434
1.00
28.27
A


ATOM
599
CB
ILE
A
150
24.303
8.325
−35.411
1.00
28.74
A


ATOM
600
CG2
ILE
A
150
23.948
7.564
−34.138
1.00
27.91
A


ATOM
601
CG1
ILE
A
150
23.518
9.634
−35.538
1.00
29.27
A


ATOM
602
CD1
ILE
A
150
22.030
9.449
−35.777
1.00
31.15
A


ATOM
603
C
ILE
A
150
26.541
7.326
−35.156
1.00
26.22
A


ATOM
604
O
ILE
A
150
26.504
6.400
−35.965
1.00
27.50
A


ATOM
605
N
VAL
A
151
27.218
7.265
−34.017
1.00
22.94
A


ATOM
606
CA
VAL
A
151
27.931
6.057
−33.629
1.00
21.78
A


ATOM
607
CB
VAL
A
151
29.468
6.322
−33.492
1.00
21.52
A


ATOM
608
CG1
VAL
A
151
29.748
7.803
−33.617
1.00
20.75
A


ATOM
609
CG2
VAL
A
151
30.001
5.774
−32.182
1.00
19.13
A


ATOM
610
C
VAL
A
151
27.319
5.577
−32.316
1.00
20.78
A


ATOM
611
O
VAL
A
151
26.936
6.390
−31.473
1.00
22.39
A


ATOM
612
N
LEU
A
152
27.196
4.264
−32.152
1.00
19.13
A


ATOM
613
CA
LEU
A
152
26.600
3.716
−30.938
1.00
19.50
A


ATOM
614
CB
LEU
A
152
25.161
3.260
−31.223
1.00
19.10
A


ATOM
615
CG
LEU
A
152
24.193
4.305
−31.798
1.00
24.16
A


ATOM
616
CD1
LEU
A
152
23.081
3.618
−32.569
1.00
24.32
A


ATOM
617
CD2
LEU
A
152
23.618
5.156
−30.677
1.00
24.79
A


ATOM
618
C
LEU
A
152
27.392
2.545
−30.353
1.00
17.69
A


ATOM
619
O
LEU
A
152
27.678
1.571
−31.049
1.00
16.33
A


ATOM
620
N
VAL
A
153
27.742
2.641
−29.073
1.00
15.12
A


ATOM
621
CA
VAL
A
153
28.466
1.563
−28.409
1.00
14.13
A


ATOM
622
CB
VAL
A
153
29.672
2.096
−27.611
1.00
13.29
A


ATOM
623
CG1
VAL
A
153
30.442
0.939
−26.997
1.00
12.78
A


ATOM
624
CG2
VAL
A
153
30.578
2.901
−28.514
1.00
14.26
A


ATOM
625
C
VAL
A
153
27.498
0.843
−27.457
1.00
15.36
A


ATOM
626
O
VAL
A
153
26.748
1.491
−26.719
1.00
12.91
A


ATOM
627
N
ASN
A
154
27.530
−0.492
−27.480
1.00
15.63
A


ATOM
628
CA
ASN
A
154
26.653
−1.334
−26.658
1.00
16.94
A


ATOM
629
CB
ASN
A
154
27.180
−1.448
−25.225
1.00
15.99
A


ATOM
630
CG
ASN
A
154
28.646
−1.828
−25.171
1.00
17.69
A


ATOM
631
OD1
ASN
A
154
29.097
−2.698
−25.915
1.00
17.61
A


ATOM
632
ND2
ASN
A
154
29.398
−1.182
−24.282
1.00
15.37
A


ATOM
633
C
ASN
A
154
25.216
−0.801
−26.632
1.00
17.66
A


ATOM
634
O
ASN
A
154
24.666
−0.510
−25.571
1.00
17.48
A


ATOM
635
N
PRO
A
155
24.588
−0.677
−27.814
1.00
18.56
A


ATOM
636
CD
PRO
A
155
25.183
−0.907
−29.138
1.00
18.26
A


ATOM
637
CA
PRO
A
155
23.215
−0.181
−27.950
1.00
18.44
A


ATOM
638
CB
PRO
A
155
23.056
0.004
−29.459
1.00
17.65
A


ATOM
639
CG
PRO
A
155
24.458
0.102
−29.966
1.00
19.09
A


ATOM
640
C
PRO
A
155
22.173
−1.157
−27.412
1.00
18.75
A


ATOM
641
O
PRO
A
155
22.277
−2.365
−27.606
1.00
19.82
A


ATOM
642
N
LYS
A
156
21.162
−0.622
−26.745
1.00
20.00
A


ATOM
643
CA
LYS
A
156
20.082
−1.441
−26.221
1.00
20.87
A


ATOM
644
CB
LYS
A
156
20.150
−1.499
−24.701
1.00
21.41
A


ATOM
645
CG
LYS
A
156
21.482
−1.949
−24.167
1.00
26.83
A


ATOM
646
CD
LYS
A
156
21.488
−1.995
−22.637
1.00
30.30
A


ATOM
647
CE
LYS
A
156
21.449
−0.601
−22.030
1.00
34.64
A


ATOM
648
NZ
LYS
A
156
21.678
−0.636
−20.551
1.00
36.85
A


ATOM
649
C
LYS
A
156
18.751
−0.824
−26.653
1.00
21.39
A


ATOM
650
O
LYS
A
156
18.532
0.388
−26.514
1.00
19.74
A


ATOM
651
N
ILE
A
157
17.869
−1.649
−27.198
1.00
22.00
A


ATOM
652
CA
ILE
A
157
16.571
−1.148
−27.616
1.00
24.95
A


ATOM
653
CB
ILE
A
157
15.983
−1.978
−28.781
1.00
24.61
A


ATOM
654
CG2
ILE
A
157
14.540
−1.559
−29.045
1.00
24.26
A


ATOM
655
CG1
ILE
A
157
16.834
−1.779
−30.038
1.00
24.91
A


ATOM
656
CD1
ILE
A
157
16.258
−2.433
−31.290
1.00
25.22
A


ATOM
657
C
ILE
A
157
15.634
−1.204
−26.422
1.00
26.62
A


ATOM
658
O
ILE
A
157
15.236
−2.284
−25.988
1.00
25.35
A


ATOM
659
N
LYS
A
158
15.306
−0.035
−25.879
1.00
30.00
A


ATOM
660
CA
LYS
A
158
14.411
0.052
−24.732
1.00
32.44
A


ATOM
661
CB
LYS
A
158
14.584
1.393
−24.009
1.00
34.21
A


ATOM
662
CG
LYS
A
158
15.822
1.460
−23.114
1.00
36.80
A


ATOM
663
CD
LYS
A
158
15.721
0.464
−21.965
1.00
37.85
A


ATOM
664
CE
LYS
A
158
17.089
0.107
−21.389
1.00
40.17
A


ATOM
665
NZ
LYS
A
158
17.827
1.271
−20.817
1.00
40.51
A


ATOM
666
C
LYS
A
158
12.969
−0.119
−25.170
1.00
32.94
A


ATOM
667
O
LYS
A
158
12.183
−0.765
−24.486
1.00
34.80
A


ATOM
668
N
LYS
A
159
12.623
0.456
−26.314
1.00
33.25
A


ATOM
669
CA
LYS
A
159
11.269
0.349
−26.834
1.00
34.87
A


ATOM
670
CB
LYS
A
159
10.367
1.438
−26.235
1.00
37.06
A


ATOM
671
CG
LYS
A
159
10.126
1.305
−24.736
1.00
40.70
A


ATOM
672
CD
LYS
A
159
9.057
2.265
−24.239
1.00
42.38
A


ATOM
673
CE
LYS
A
159
8.687
1.963
−22.787
1.00
44.63
A


ATOM
674
NZ
LYS
A
159
7.473
2.710
−22.322
1.00
46.12
A


ATOM
675
C
LYS
A
159
11.269
0.495
−28.340
1.00
34.89
A


ATOM
676
O
LYS
A
159
12.135
1.161
−28.903
1.00
35.59
A


ATOM
677
N
TYR
A
160
10.311
−0.147
−28.996
1.00
35.44
A


ATOM
678
CA
TYR
A
160
10.187
−0.025
−30.439
1.00
36.62
A


ATOM
679
CB
TYR
A
160
10.842
−1.208
−31.162
1.00
42.19
A


ATOM
680
CG
TYR
A
160
10.445
−2.569
−30.673
1.00
47.11
A


ATOM
681
CD1
TYR
A
160
9.143
−3.037
−30.838
1.00
50.34
A


ATOM
682
CE1
TYR
A
160
8.776
−4.314
−30.407
1.00
53.27
A


ATOM
683
CD2
TYR
A
160
11.381
−3.405
−30.062
1.00
49.07
A


ATOM
684
CE2
TYR
A
160
11.030
−4.677
−29.626
1.00
52.79
A


ATOM
685
CZ
TYR
A
160
9.723
−5.129
−29.802
1.00
54.17
A


ATOM
686
OH
TYR
A
160
9.363
−6.395
−29.381
1.00
56.97
A


ATOM
687
C
TYR
A
160
8.718
0.129
−30.812
1.00
33.35
A


ATOM
688
O
TYR
A
160
7.833
−0.296
−30.077
1.00
33.80
A


ATOM
689
N
SER
A
161
8.469
0.770
−31.945
1.00
28.83
A


ATOM
690
CA
SER
A
161
7.117
1.037
−32.406
1.00
25.47
A


ATOM
691
CB
SER
A
161
7.175
1.761
−33.756
1.00
25.05
A


ATOM
692
OG
SER
A
161
5.877
2.039
−34.248
1.00
25.20
A


ATOM
693
C
SER
A
161
6.227
−0.194
−32.525
1.00
24.00
A


ATOM
694
O
SER
A
161
6.699
−1.310
−32.736
1.00
25.13
A


ATOM
695
N
ASP
A
162
4.927
0.016
−32.377
1.00
20.81
A


ATOM
696
CA
ASP
A
162
3.988
−1.078
−32.512
1.00
18.67
A


ATOM
697
CB
ASP
A
162
2.924
−1.012
−31.404
1.00
17.74
A


ATOM
698
CG
ASP
A
162
2.043
0.224
−31.491
1.00
20.48
A


ATOM
699
OD1
ASP
A
162
2.411
1.197
−32.193
1.00
19.28
A


ATOM
700
OD2
ASP
A
162
0.974
0.216
−30.832
1.00
20.44
A


ATOM
701
C
ASP
A
162
3.361
−1.031
−33.917
1.00
17.19
A


ATOM
702
O
ASP
A
162
2.405
−1.748
−34.214
1.00
16.88
A


ATOM
703
N
LYS
A
163
3.922
−0.185
−34.778
1.00
13.19
A


ATOM
704
CA
LYS
A
163
3.458
−0.060
−36.157
1.00
14.42
A


ATOM
705
CB
LYS
A
163
3.063
1.392
−36.465
1.00
17.11
A


ATOM
706
CG
LYS
A
163
2.008
1.943
−35.516
1.00
21.55
A


ATOM
707
CD
LYS
A
163
1.511
3.321
−35.933
1.00
25.69
A


ATOM
708
CE
LYS
A
163
0.470
3.836
−34.942
1.00
26.67
A


ATOM
709
NZ
LYS
A
163
−0.163
5.115
−35.373
1.00
30.99
A


ATOM
710
C
LYS
A
163
4.563
−0.515
−37.114
1.00
14.12
A


ATOM
711
O
LYS
A
163
5.709
−0.067
−37.029
1.00
11.38
A


ATOM
712
N
LEU
A
164
4.207
−1.405
−38.032
1.00
14.88
A


ATOM
713
CA
LEU
A
164
5.167
−1.934
−38.987
1.00
15.75
A


ATOM
714
CB
LEU
A
164
4.933
−3.430
−39.182
1.00
16.05
A


ATOM
715
CG
LEU
A
164
5.202
−4.299
−37.953
1.00
17.46
A


ATOM
716
CD1
LEU
A
164
4.720
−5.716
−38.219
1.00
15.64
A


ATOM
717
CD2
LEU
A
164
6.696
−4.269
−37.617
1.00
16.61
A


ATOM
718
C
LEU
A
164
5.153
−1.251
−40.340
1.00
17.09
A


ATOM
719
O
LEU
A
164
4.097
−0.893
−40.865
1.00
17.75
A


ATOM
720
N
VAL
A
165
6.343
−1.066
−40.900
1.00
17.38
A


ATOM
721
CA
VAL
A
165
6.466
−0.457
−42.209
1.00
18.26
A


ATOM
722
CB
VAL
A
165
6.899
1.017
−42.118
1.00
16.51
A


ATOM
723
CG1
VAL
A
165
5.763
1.841
−41.511
1.00
16.42
A


ATOM
724
CG2
VAL
A
165
8.172
1.145
−41.290
1.00
17.21
A


ATOM
725
C
VAL
A
165
7.469
−1.243
−43.045
1.00
19.14
A


ATOM
726
O
VAL
A
165
8.433
−1.808
−42.518
1.00
20.01
A


ATOM
727
N
PRO
A
166
7.234
−1.316
−44.362
1.00
19.02
A


ATOM
728
CD
PRO
A
166
5.982
−0.965
−45.062
1.00
18.32
A


ATOM
729
CA
PRO
A
166
8.137
−2.047
−45.251
1.00
20.65
A


ATOM
730
CB
PRO
A
166
7.195
−2.543
−46.340
1.00
20.89
A


ATOM
731
CG
PRO
A
166
6.284
−1.350
−46.503
1.00
19.48
A


ATOM
732
C
PRO
A
166
9.222
−1.132
−45.805
1.00
21.42
A


ATOM
733
O
PRO
A
166
9.073
0.087
−45.803
1.00
21.01
A


ATOM
734
N
PHE
A
167
10.312
−1.728
−46.275
1.00
23.28
A


ATOM
735
CA
PHE
A
167
11.405
−0.966
−46.859
1.00
25.18
A


ATOM
736
CB
PHE
A
167
12.141
−0.176
−45.779
1.00
28.27
A


ATOM
737
CG
PHE
A
167
13.095
0.840
−46.325
1.00
33.26
A


ATOM
738
CD1
PHE
A
167
12.637
2.083
−46.751
1.00
35.31
A


ATOM
739
CD2
PHE
A
167
14.450
0.540
−46.459
1.00
36.84
A


ATOM
740
CE1
PHE
A
167
13.514
3.022
−47.308
1.00
37.46
A


ATOM
741
CE2
PHE
A
167
15.341
1.468
−47.014
1.00
38.88
A


ATOM
742
CZ
PHE
A
167
14.870
2.714
−47.440
1.00
38.07
A


ATOM
743
C
PHE
A
167
12.375
−1.919
−47.547
1.00
24.62
A


ATOM
744
O
PHE
A
167
12.677
−2.981
−47.010
1.00
24.38
A


ATOM
745
N
ASP
A
168
12.837
−1.562
−48.745
1.00
25.04
A


ATOM
746
CA
ASP
A
168
13.791
−2.414
−49.456
1.00
25.00
A


ATOM
747
CB
ASP
A
168
13.804
−2.116
−50.958
1.00
27.03
A


ATOM
748
CG
ASP
A
168
12.478
−2.418
−51.629
1.00
28.34
A


ATOM
749
OD1
ASP
A
168
11.679
−3.193
−51.063
1.00
30.93
A


ATOM
750
OD2
ASP
A
168
12.239
−1.890
−52.736
1.00
31.05
A


ATOM
751
C
ASP
A
168
15.155
−2.113
−48.861
1.00
24.01
A


ATOM
752
O
ASP
A
168
15.679
−1.010
−49.002
1.00
23.88
A


ATOM
753
N
GLU
A
169
15.723
−3.095
−48.182
1.00
23.69
A


ATOM
754
CA
GLU
A
169
17.011
−2.908
−47.532
1.00
23.00
A


ATOM
755
CB
GLU
A
169
16.997
−3.555
−46.149
1.00
23.01
A


ATOM
756
CG
GLU
A
169
16.073
−2.907
−45.142
1.00
24.80
A


ATOM
757
CD
GLU
A
169
16.034
−3.679
−43.833
1.00
25.40
A


ATOM
758
OE1
GLU
A
169
17.108
−4.145
−43.398
1.00
24.55
A


ATOM
759
OE2
GLU
A
169
14.940
−3.814
−43.240
1.00
25.14
A


ATOM
760
C
GLU
A
169
18.182
−3.478
−48.305
1.00
21.78
A


ATOM
761
O
GLU
A
169
18.068
−4.495
−48.979
1.00
21.39
A


ATOM
762
N
GLY
A
170
19.312
−2.797
−48.196
1.00
20.18
A


ATOM
763
CA
GLY
A
170
20.526
−3.262
−48.826
1.00
19.41
A


ATOM
764
C
GLY
A
170
21.488
−3.541
−47.684
1.00
19.42
A


ATOM
765
O
GLY
A
170
21.205
−3.179
−46.533
1.00
18.09
A


ATOM
766
N
CYS
A
171
22.609
−4.189
−47.983
1.00
17.85
A


ATOM
767
CA
CYS
A
171
23.617
−4.495
−46.973
1.00
17.78
A


ATOM
768
CB
CYS
A
171
23.274
−5.793
−46.222
1.00
17.35
A


ATOM
769
SG
CYS
A
171
24.482
−6.273
−44.946
1.00
17.05
A


ATOM
770
C
CYS
A
171
24.956
−4.644
−47.667
1.00
17.66
A


ATOM
771
O
CYS
A
171
25.051
−5.264
−48.731
1.00
18.62
A


ATOM
772
N
LEU
A
172
25.988
−4.071
−47.060
1.00
18.65
A


ATOM
773
CA
LEU
A
172
27.337
−4.120
−47.607
1.00
17.51
A


ATOM
774
CB
LEU
A
172
28.268
−3.218
−46.780
1.00
18.35
A


ATOM
775
CG
LEU
A
172
28.433
−1.739
−47.177
1.00
18.16
A


ATOM
776
CD1
LEU
A
172
27.382
−1.317
−48.180
1.00
19.26
A


ATOM
777
CD2
LEU
A
172
28.373
−0.875
−45.930
1.00
17.19
A


ATOM
778
C
LEU
A
172
27.895
−5.537
−47.672
1.00
17.16
A


ATOM
779
O
LEU
A
172
28.819
−5.811
−48.438
1.00
19.43
A


ATOM
780
N
SER
A
173
27.335
−6.442
−46.879
1.00
15.56
A


ATOM
781
CA
SER
A
173
27.807
−7.822
−46.880
1.00
15.09
A


ATOM
782
CB
SER
A
173
27.627
−8.438
−45.498
1.00
13.35
A


ATOM
783
OG
SER
A
173
28.432
−7.766
−44.542
1.00
13.38
A


ATOM
784
C
SER
A
173
27.077
−8.668
−47.920
1.00
16.25
A


ATOM
785
O
SER
A
173
27.318
−9.872
−48.037
1.00
16.75
A


ATOM
786
N
PHE
A
174
26.180
−8.029
−48.664
1.00
16.57
A


ATOM
787
CA
PHE
A
174
25.396
−8.688
−49.709
1.00
17.10
A


ATOM
788
CB
PHE
A
174
23.954
−8.905
−49.235
1.00
18.18
A


ATOM
789
CG
PHE
A
174
23.819
−9.875
−48.085
1.00
17.61
A


ATOM
790
CD1
PHE
A
174
23.432
−11.196
−48.313
1.00
17.43
A


ATOM
791
CD2
PHE
A
174
24.047
−9.461
−46.775
1.00
18.73
A


ATOM
792
CE1
PHE
A
174
23.267
−12.091
−47.253
1.00
16.70
A


ATOM
793
CE2
PHE
A
174
23.887
−10.352
−45.703
1.00
19.19
A


ATOM
794
CZ
PHE
A
174
23.495
−11.670
−45.946
1.00
18.29
A


ATOM
795
C
PHE
A
174
25.413
−7.748
−50.916
1.00
16.80
A


ATOM
796
O
PHE
A
174
24.402
−7.142
−51.276
1.00
16.00
A


ATOM
797
N
PRO
A
175
26.576
−7.627
−51.562
1.00
18.42
A


ATOM
798
CD
PRO
A
175
27.766
−8.470
−51.335
1.00
17.82
A


ATOM
799
CA
PRO
A
175
26.771
−6.762
−52.728
1.00
19.70
A


ATOM
800
CB
PRO
A
175
28.048
−7.317
−53.350
1.00
20.05
A


ATOM
801
CG
PRO
A
175
28.826
−7.755
−52.138
1.00
18.23
A


ATOM
802
C
PRO
A
175
25.617
−6.700
−53.716
1.00
20.20
A


ATOM
803
O
PRO
A
175
25.240
−7.710
−54.312
1.00
20.33
A


ATOM
804
N
GLY
A
176
25.059
−5.497
−53.866
1.00
21.23
A


ATOM
805
CA
GLY
A
176
23.968
−5.260
−54.800
1.00
19.68
A


ATOM
806
C
GLY
A
176
22.669
−6.019
−54.598
1.00
18.84
A


ATOM
807
O
GLY
A
176
21.826
−6.065
−55.498
1.00
16.30
A


ATOM
808
N
ILE
A
177
22.487
−6.621
−53.430
1.00
18.40
A


ATOM
809
CA
ILE
A
177
21.256
−7.355
−53.186
1.00
19.40
A


ATOM
810
CB
ILE
A
177
21.547
−8.683
−52.450
1.00
19.34
A


ATOM
811
CG2
ILE
A
177
20.250
−9.372
−52.066
1.00
20.31
A


ATOM
812
CG1
ILE
A
177
22.398
−9.584
−53.352
1.00
20.29
A


ATOM
813
CD1
ILE
A
177
22.776
−10.927
−52.735
1.00
18.41
A


ATOM
814
C
ILE
A
177
20.278
−6.498
−52.391
1.00
19.23
A


ATOM
815
O
ILE
A
177
20.642
−5.904
−51.378
1.00
18.56
A


ATOM
816
N
TYR
A
178
19.043
−6.408
−52.878
1.00
20.54
A


ATOM
817
CA
TYR
A
178
18.014
−5.624
−52.199
1.00
22.95
A


ATOM
818
CB
TYR
A
178
17.813
−4.266
−52.879
1.00
24.10
A


ATOM
819
CG
TYR
A
178
19.064
−3.420
−52.962
1.00
27.38
A


ATOM
820
CD1
TYR
A
178
20.069
−3.721
−53.888
1.00
26.85
A


ATOM
821
CE1
TYR
A
178
21.235
−2.962
−53.962
1.00
27.02
A


ATOM
822
CD2
TYR
A
178
19.258
−2.330
−52.106
1.00
26.90
A


ATOM
823
CE2
TYR
A
178
20.431
−1.560
−52.176
1.00
28.14
A


ATOM
824
CZ
TYR
A
178
21.414
−1.888
−53.111
1.00
28.84
A


ATOM
825
OH
TYR
A
178
22.577
−1.147
−53.210
1.00
30.05
A


ATOM
826
C
TYR
A
178
16.680
−6.352
−52.154
1.00
22.69
A


ATOM
827
O
TYR
A
178
16.192
−6.839
−53.175
1.00
23.47
A


ATOM
828
N
ALA
A
179
16.095
−6.430
−50.965
1.00
21.13
A


ATOM
829
CA
ALA
A
179
14.801
−7.085
−50.800
1.00
21.16
A


ATOM
830
CB
ALA
A
179
14.991
−8.557
−50.478
1.00
20.57
A


ATOM
831
C
ALA
A
179
14.021
−6.390
−49.697
1.00
21.14
A


ATOM
832
O
ALA
A
179
14.597
−5.699
−48.855
1.00
21.11
A


ATOM
833
N
GLU
A
180
12.706
−6.569
−49.706
1.00
21.61
A


ATOM
834
CA
GLU
A
180
11.842
−5.929
−48.721
1.00
22.07
A


ATOM
835
CB
GLU
A
180
10.399
−5.943
−49.230
1.00
24.22
A


ATOM
836
CG
GLU
A
180
9.437
−5.163
−48.352
1.00
27.20
A


ATOM
837
CD
GLU
A
180
8.021
−5.150
−48.893
1.00
27.70
A


ATOM
838
OE1
GLU
A
180
7.245
−6.075
−48.568
1.00
27.79
A


ATOM
839
OE2
GLU
A
180
7.691
−4.210
−49.649
1.00
27.64
A


ATOM
840
C
GLU
A
180
11.880
−6.526
−47.306
1.00
20.52
A


ATOM
841
O
GLU
A
180
11.805
−7.736
−47.124
1.00
20.89
A


ATOM
842
N
VAL
A
181
11.993
−5.664
−46.304
1.00
19.74
A


ATOM
843
CA
VAL
A
181
11.995
−6.112
−44.916
1.00
20.39
A


ATOM
844
CB
VAL
A
181
13.399
−5.964
−44.264
1.00
20.82
A


ATOM
845
CG1
VAL
A
181
13.372
−6.508
−42.840
1.00
20.17
A


ATOM
846
CG2
VAL
A
181
14.450
−6.708
−45.089
1.00
18.51
A


ATOM
847
C
VAL
A
181
10.984
−5.268
−44.136
1.00
20.46
A


ATOM
848
O
VAL
A
181
10.877
−4.063
−44.352
1.00
20.70
A


ATOM
849
N
VAL
A
182
10.224
−5.901
−43.248
1.00
20.35
A


ATOM
850
CA
VAL
A
182
9.235
−5.183
−42.443
1.00
19.16
A


ATOM
851
CB
VAL
A
182
7.881
−5.935
−42.419
1.00
20.20
A


ATOM
852
CG1
VAL
A
182
6.865
−5.168
−41.587
1.00
19.98
A


ATOM
853
CG2
VAL
A
182
7.365
−6.120
−43.841
1.00
20.58
A


ATOM
854
C
VAL
A
182
9.738
−5.020
−41.011
1.00
17.95
A


ATOM
855
O
VAL
A
182
10.083
−6.001
−40.353
1.00
18.95
A


ATOM
856
N
ARG
A
183
9.789
−3.781
−40.531
1.00
16.50
A


ATOM
857
CA
ARG
A
183
10.257
−3.516
−39.169
1.00
14.82
A


ATOM
858
CB
ARG
A
183
11.713
−3.036
−39.167
1.00
15.48
A


ATOM
859
CG
ARG
A
183
12.749
−3.901
−39.862
1.00
12.14
A


ATOM
860
CD
ARG
A
183
14.098
−3.199
−39.730
1.00
13.95
A


ATOM
861
NE
ARG
A
183
15.172
−3.826
−40.492
1.00
14.27
A


ATOM
862
CZ
ARG
A
183
15.907
−4.844
−40.062
1.00
14.82
A


ATOM
863
NH1
ARG
A
183
15.687
−5.361
−38.856
1.00
13.88
A


ATOM
864
NH2
ARG
A
183
16.863
−5.342
−40.845
1.00
10.27
A


ATOM
865
C
ARG
A
183
9.436
−2.421
−38.502
1.00
15.01
A


ATOM
866
O
ARG
A
183
8.731
−1.658
−39.172
1.00
13.85
A


ATOM
867
N
PRO
A
184
9.512
−2.332
−37.161
1.00
14.58
A


ATOM
868
CD
PRO
A
184
10.141
−3.264
−36.206
1.00
13.75
A


ATOM
869
CA
PRO
A
184
8.764
−1.285
−36.458
1.00
14.05
A


ATOM
870
CB
PRO
A
184
9.171
−1.496
−35.001
1.00
13.48
A


ATOM
871
CG
PRO
A
184
9.379
−2.981
−34.926
1.00
13.61
A


ATOM
872
C
PRO
A
184
9.287
0.035
−37.030
1.00
13.54
A


ATOM
873
O
PRO
A
184
10.463
0.123
−37.394
1.00
12.47
A


ATOM
874
N
GLN
A
185
8.437
1.052
−37.121
1.00
14.24
A


ATOM
875
CA
GLN
A
185
8.867
2.326
−37.703
1.00
16.35
A


ATOM
876
CB
GLN
A
185
7.647
3.160
−38.144
1.00
16.49
A


ATOM
877
CG
GLN
A
185
6.647
3.488
−37.053
1.00
18.19
A


ATOM
878
CD
GLN
A
185
5.486
4.339
−37.562
1.00
20.93
A


ATOM
879
OE1
GLN
A
185
5.126
4.276
−38.735
1.00
22.48
A


ATOM
880
NE2
GLN
A
185
4.886
5.126
−36.672
1.00
19.77
A


ATOM
881
C
GLN
A
185
9.783
3.191
−36.843
1.00
16.52
A


ATOM
882
O
GLN
A
185
10.467
4.071
−37.358
1.00
16.86
A


ATOM
883
N
SER
A
186
9.804
2.951
−35.540
1.00
17.54
A


ATOM
884
CA
SER
A
186
10.642
3.749
−34.655
1.00
17.28
A


ATOM
885
CB
SER
A
186
9.888
4.984
−34.193
1.00
16.83
A


ATOM
886
OG
SER
A
186
8.814
4.597
−33.365
1.00
16.18
A


ATOM
887
C
SER
A
186
11.087
2.963
−33.433
1.00
18.56
A


ATOM
888
O
SER
A
186
10.483
1.948
−33.072
1.00
17.15
A


ATOM
889
N
VAL
A
187
12.145
3.454
−32.794
1.00
18.41
A


ATOM
890
CA
VAL
A
187
12.707
2.812
−31.614
1.00
17.19
A


ATOM
891
CB
VAL
A
187
13.880
1.875
−31.990
1.00
16.71
A


ATOM
892
CG1
VAL
A
187
13.376
0.651
−32.717
1.00
14.52
A


ATOM
893
CG2
VAL
A
187
14.868
2.629
−32.869
1.00
16.52
A


ATOM
894
C
VAL
A
187
13.257
3.845
−30.643
1.00
19.68
A


ATOM
895
O
VAL
A
187
13.471
5.012
−30.991
1.00
17.36
A


ATOM
896
N
LYS
A
188
13.488
3.379
−29.422
1.00
22.44
A


ATOM
897
CA
LYS
A
188
14.041
4.170
−28.333
1.00
24.50
A


ATOM
898
CB
LYS
A
188
13.044
4.223
−27.175
1.00
27.86
A


ATOM
899
CG
LYS
A
188
13.634
4.704
−25.858
1.00
32.55
A


ATOM
900
CD
LYS
A
188
12.604
4.645
−24.724
1.00
37.24
A


ATOM
901
CE
LYS
A
188
11.438
5.613
−24.952
1.00
39.23
A


ATOM
902
NZ
LYS
A
188
10.474
5.621
−23.803
1.00
40.21
A


ATOM
903
C
LYS
A
188
15.291
3.399
−27.925
1.00
24.24
A


ATOM
904
O
LYS
A
188
15.202
2.222
−27.574
1.00
25.34
A


ATOM
905
N
ILE
A
189
16.449
4.049
−27.976
1.00
25.02
A


ATOM
906
CA
ILE
A
189
17.707
3.382
−27.648
1.00
25.74
A


ATOM
907
CB
ILE
A
189
18.677
3.413
−28.853
1.00
25.43
A


ATOM
908
CG2
ILE
A
189
19.959
2.665
−28.520
1.00
27.70
A


ATOM
909
CG1
ILE
A
189
18.010
2.801
−30.084
1.00
25.02
A


ATOM
910
CD1
ILE
A
189
17.209
3.794
−30.886
1.00
26.73
A


ATOM
911
C
ILE
A
189
18.476
3.936
−26.452
1.00
26.55
A


ATOM
912
O
ILE
A
189
18.340
5.098
−26.080
1.00
28.56
A


ATOM
913
N
ASP
A
190
19.296
3.071
−25.867
1.00
26.77
A


ATOM
914
CA
ASP
A
190
20.167
3.398
−24.745
1.00
25.30
A


ATOM
915
CB
ASP
A
190
19.769
2.591
−23.506
1.00
27.91
A


ATOM
916
CG
ASP
A
190
19.126
3.447
−22.425
1.00
29.11
A


ATOM
917
OD1
ASP
A
190
18.312
4.335
−22.757
1.00
32.09
A


ATOM
918
OD2
ASP
A
190
19.428
3.220
−21.235
1.00
31.65
A


ATOM
919
C
ASP
A
190
21.527
2.930
−25.249
1.00
23.53
A


ATOM
920
O
ASP
A
190
21.631
1.846
−25.814
1.00
25.23
A


ATOM
921
N
ALA
A
191
22.564
3.735
−25.073
1.00
20.98
A


ATOM
922
CA
ALA
A
191
23.889
3.339
−25.536
1.00
19.22
A


ATOM
923
CB
ALA
A
191
23.975
3.501
−27.052
1.00
16.43
A


ATOM
924
C
ALA
A
191
24.961
4.179
−24.869
1.00
16.73
A


ATOM
925
O
ALA
A
191
24.659
5.021
−24.031
1.00
14.46
A


ATOM
926
N
ARG
A
192
26.215
3.932
−25.241
1.00
17.62
A


ATOM
927
CA
ARG
A
192
27.344
4.701
−24.719
1.00
16.89
A


ATOM
928
CB
ARG
A
192
28.344
3.813
−23.983
1.00
14.64
A


ATOM
929
CG
ARG
A
192
27.849
3.112
−22.736
1.00
16.43
A


ATOM
930
CD
ARG
A
192
28.933
2.152
−22.266
1.00
14.30
A


ATOM
931
NE
ARG
A
192
28.564
1.361
−21.099
1.00
17.12
A


ATOM
932
CZ
ARG
A
192
28.434
1.847
−19.868
1.00
17.79
A


ATOM
933
NH1
ARG
A
192
28.638
3.137
−19.629
1.00
18.41
A


ATOM
934
NH2
ARG
A
192
28.116
1.035
−18.869
1.00
16.93
A


ATOM
935
C
ARG
A
192
28.060
5.305
−25.921
1.00
16.09
A


ATOM
936
O
ARG
A
192
27.943
4.800
−27.029
1.00
14.43
A


ATOM
937
N
ASP
A
193
28.808
6.378
−25.691
1.00
17.73
A


ATOM
938
CA
ASP
A
193
29.574
7.023
−26.750
1.00
19.68
A


ATOM
939
CB
ASP
A
193
29.559
8.543
−26.557
1.00
21.17
A


ATOM
940
CG
ASP
A
193
30.420
8.997
−25.394
1.00
22.73
A


ATOM
941
OD1
ASP
A
193
30.523
8.270
−24.381
1.00
23.37
A


ATOM
942
OD2
ASP
A
193
30.991
10.101
−25.493
1.00
26.89
A


ATOM
943
C
ASP
A
193
30.997
6.462
−26.634
1.00
19.97
A


ATOM
944
O
ASP
A
193
31.235
5.571
−25.815
1.00
17.40
A


ATOM
945
N
ILE
A
194
31.937
6.971
−27.430
1.00
20.45
A


ATOM
946
CA
ILE
A
194
33.304
6.451
−27.385
1.00
21.45
A


ATOM
947
CB
ILE
A
194
34.173
6.962
−28.554
1.00
21.84
A


ATOM
948
CG2
ILE
A
194
33.679
6.381
−29.862
1.00
22.88
A


ATOM
949
CG1
ILE
A
194
34.180
8.488
−28.592
1.00
22.27
A


ATOM
950
CD1
ILE
A
194
35.136
9.058
−29.644
1.00
23.29
A


ATOM
951
C
ILE
A
194
34.057
6.732
−26.093
1.00
22.29
A


ATOM
952
O
ILE
A
194
35.073
6.098
−25.824
1.00
23.35
A


ATOM
953
N
THR
A
195
33.574
7.676
−25.292
1.00
21.53
A


ATOM
954
CA
THR
A
195
34.248
7.978
−24.035
1.00
22.32
A


ATOM
955
CB
THR
A
195
34.119
9.478
−23.636
1.00
21.72
A


ATOM
956
OG1
THR
A
195
32.741
9.811
−23.418
1.00
18.57
A


ATOM
957
CG2
THR
A
195
34.694
10.370
−24.723
1.00
20.26
A


ATOM
958
C
THR
A
195
33.632
7.118
−22.941
1.00
22.63
A


ATOM
959
O
THR
A
195
34.074
7.143
−21.791
1.00
21.86
A


ATOM
960
N
GLY
A
196
32.601
6.363
−23.313
1.00
23.03
A


ATOM
961
CA
GLY
A
196
31.930
5.493
−22.365
1.00
23.21
A


ATOM
962
C
GLY
A
196
30.759
6.147
−21.660
1.00
24.01
A


ATOM
963
O
GLY
A
196
30.146
5.535
−20.792
1.00
23.82
A


ATOM
964
N
GLU
A
197
30.445
7.389
−22.019
1.00
26.36
A


ATOM
965
CA
GLU
A
197
29.325
8.080
−21.391
1.00
27.87
A


ATOM
966
CB
GLU
A
197
29.437
9.598
−21.558
1.00
30.06
A


ATOM
967
CG
GLU
A
197
30.667
10.225
−20.908
1.00
35.75
A


ATOM
968
CD
GLU
A
197
30.787
9.923
−19.420
1.00
39.16
A


ATOM
969
OE1
GLU
A
197
31.824
10.299
−18.825
1.00
42.10
A


ATOM
970
OE2
GLU
A
197
29.857
9.312
−18.844
1.00
39.72
A


ATOM
971
C
GLU
A
197
28.037
7.593
−22.020
1.00
27.80
A


ATOM
972
O
GLU
A
197
27.955
7.420
−23.236
1.00
28.26
A


ATOM
973
N
ARG
A
198
27.031
7.365
−21.189
1.00
28.14
A


ATOM
974
CA
ARG
A
198
25.753
6.885
−21.682
1.00
28.82
A


ATOM
975
CB
ARG
A
198
24.991
6.185
−20.561
1.00
32.41
A


ATOM
976
CG
ARG
A
198
25.853
5.255
−19.720
1.00
37.31
A


ATOM
977
CD
ARG
A
198
25.068
4.036
−19.282
1.00
42.63
A


ATOM
978
NE
ARG
A
198
24.541
3.322
−20.444
1.00
46.58
A


ATOM
979
CZ
ARG
A
198
24.024
2.100
−20.403
1.00
48.75
A


ATOM
980
NH1
ARG
A
198
23.964
1.445
−19.247
1.00
48.98
A


ATOM
981
NH2
ARG
A
198
23.564
1.535
−21.518
1.00
48.98
A


ATOM
982
C
ARG
A
198
24.900
8.016
−22.243
1.00
27.54
A


ATOM
983
O
ARG
A
198
25.071
9.189
−21.891
1.00
27.87
A


ATOM
984
N
PHE
A
199
23.986
7.653
−23.132
1.00
25.20
A


ATOM
985
CA
PHE
A
199
23.079
8.613
−23.728
1.00
23.21
A


ATOM
986
CB
PHE
A
199
23.769
9.393
−24.858
1.00
21.17
A


ATOM
987
CG
PHE
A
199
24.088
8.572
−26.084
1.00
19.11
A


ATOM
988
CD1
PHE
A
199
23.124
8.359
−27.070
1.00
17.06
A


ATOM
989
CD2
PHE
A
199
25.373
8.049
−26.273
1.00
18.18
A


ATOM
990
CE1
PHE
A
199
23.437
7.639
−28.232
1.00
17.14
A


ATOM
991
CE2
PHE
A
199
25.698
7.328
−27.425
1.00
14.22
A


ATOM
992
CZ
PHE
A
199
24.731
7.124
−28.407
1.00
16.27
A


ATOM
993
C
PHE
A
199
21.859
7.871
−24.243
1.00
23.72
A


ATOM
994
O
PHE
A
199
21.898
6.659
−24.450
1.00
21.75
A


ATOM
995
N
SER
A
200
20.769
8.600
−24.431
1.00
25.35
A


ATOM
996
CA
SER
A
200
19.541
8.000
−24.915
1.00
26.06
A


ATOM
997
CB
SER
A
200
18.551
7.844
−23.767
1.00
26.35
A


ATOM
998
OG
SER
A
200
19.115
7.060
−22.732
1.00
29.16
A


ATOM
999
C
SER
A
200
18.941
8.867
−25.996
1.00
26.17
A


ATOM
1000
O
SER
A
200
18.994
10.092
−25.915
1.00
27.31
A


ATOM
1001
N
ILE
A
201
18.376
8.226
−27.013
1.00
26.58
A


ATOM
1002
CA
ILE
A
201
17.756
8.942
−28.118
1.00
26.23
A


ATOM
1003
CB
ILE
A
201
18.762
9.214
−29.250
1.00
28.26
A


ATOM
1004
CG2
ILE
A
201
19.813
10.216
−28.790
1.00
29.33
A


ATOM
1005
CG1
ILE
A
201
19.394
7.895
−29.701
1.00
28.98
A


ATOM
1006
CD1
ILE
A
201
20.230
8.010
−30.962
1.00
31.66
A


ATOM
1007
C
ILE
A
201
16.593
8.152
−28.709
1.00
25.11
A


ATOM
1008
O
ILE
A
201
16.418
6.958
−28.434
1.00
23.45
A


ATOM
1009
N
SER
A
202
15.796
8.833
−29.522
1.00
24.09
A


ATOM
1010
CA
SER
A
202
14.657
8.209
−30.180
1.00
23.76
A


ATOM
1011
CB
SER
A
202
13.356
8.918
−29.802
1.00
23.27
A


ATOM
1012
OG
SER
A
202
13.018
8.677
−28.447
1.00
26.12
A


ATOM
1013
C
SER
A
202
14.864
8.297
−31.676
1.00
22.76
A


ATOM
1014
O
SER
A
202
15.181
9.357
−32.205
1.00
20.95
A


ATOM
1015
N
LEU
A
203
14.708
7.178
−32.364
1.00
22.93
A


ATOM
1016
CA
LEU
A
203
14.871
7.193
−33.804
1.00
23.93
A


ATOM
1017
CB
LEU
A
203
16.005
6.257
−34.237
1.00
23.48
A


ATOM
1018
CG
LEU
A
203
17.387
6.575
−33.669
1.00
23.22
A


ATOM
1019
CD1
LEU
A
203
18.414
5.669
−34.321
1.00
23.21
A


ATOM
1020
CD2
LEU
A
203
17.727
8.039
−33.914
1.00
21.89
A


ATOM
1021
C
LEU
A
203
13.585
6.795
−34.498
1.00
23.86
A


ATOM
1022
O
LEU
A
203
12.781
6.024
−33.966
1.00
24.42
A


ATOM
1023
N
SER
A
204
13.396
7.350
−35.685
1.00
25.11
A


ATOM
1024
CA
SER
A
204
12.237
7.060
−36.514
1.00
27.28
A


ATOM
1025
CB
SER
A
204
11.111
8.051
−36.236
1.00
28.55
A


ATOM
1026
OG
SER
A
204
11.482
9.351
−36.658
1.00
30.10
A


ATOM
1027
C
SER
A
204
12.741
7.248
−37.934
1.00
27.55
A


ATOM
1028
O
SER
A
204
13.933
7.502
−38.137
1.00
27.70
A


ATOM
1029
N
ARG
A
205
11.845
7.133
−38.910
1.00
28.31
A


ATOM
1030
CA
ARG
A
205
12.221
7.315
−40.307
1.00
28.06
A


ATOM
1031
CB
ARG
A
205
12.594
8.777
−40.569
1.00
31.86
A


ATOM
1032
CG
ARG
A
205
11.428
9.756
−40.709
1.00
36.98
A


ATOM
1033
CD
ARG
A
205
11.988
11.169
−40.867
1.00
40.88
A


ATOM
1034
NE
ARG
A
205
11.122
12.070
−41.621
1.00
44.32
A


ATOM
1035
CZ
ARG
A
205
11.423
13.343
−41.879
1.00
47.87
A


ATOM
1036
NH1
ARG
A
205
12.568
13.861
−41.442
1.00
48.05
A


ATOM
1037
NH2
ARG
A
205
10.583
14.107
−42.573
1.00
48.10
A


ATOM
1038
C
ARG
A
205
13.396
6.424
−40.706
1.00
25.68
A


ATOM
1039
O
ARG
A
205
13.523
5.293
−40.235
1.00
24.48
A


ATOM
1040
N
LEU
A
206
14.261
6.958
−41.563
1.00
21.87
A


ATOM
1041
CA
LEU
A
206
15.413
6.219
−42.057
1.00
19.85
A


ATOM
1042
CB
LEU
A
206
16.115
7.006
−43.166
1.00
20.52
A


ATOM
1043
CG
LEU
A
206
17.278
6.277
−43.856
1.00
23.37
A


ATOM
1044
CD1
LEU
A
206
16.765
5.016
−44.565
1.00
20.22
A


ATOM
1045
CD2
LEU
A
206
17.951
7.217
−44.853
1.00
22.79
A


ATOM
1046
C
LEU
A
206
16.420
5.854
−40.974
1.00
18.21
A


ATOM
1047
O
LEU
A
206
16.921
4.727
−40.953
1.00
16.21
A


ATOM
1048
N
PRO
A
207
16.742
6.799
−40.069
1.00
16.71
A


ATOM
1049
CD
PRO
A
207
16.439
8.245
−40.087
1.00
17.35
A


ATOM
1050
CA
PRO
A
207
17.709
6.487
−39.008
1.00
17.46
A


ATOM
1051
CB
PRO
A
207
17.795
7.794
−38.217
1.00
16.29
A


ATOM
1052
CG
PRO
A
207
17.588
8.828
−39.283
1.00
16.84
A


ATOM
1053
C
PRO
A
207
17.264
5.305
−38.154
1.00
16.91
A


ATOM
1054
O
PRO
A
207
18.084
4.484
−37.747
1.00
18.14
A


ATOM
1055
N
ALA
A
208
15.963
5.212
−37.896
1.00
16.46
A


ATOM
1056
CA
ALA
A
208
15.437
4.106
−37.104
1.00
15.91
A


ATOM
1057
CB
ALA
A
208
13.967
4.344
−36.780
1.00
16.38
A


ATOM
1058
C
ALA
A
208
15.597
2.800
−37.883
1.00
14.15
A


ATOM
1059
O
ALA
A
208
15.932
1.763
−37.320
1.00
14.30
A


ATOM
1060
N
ARG
A
209
15.357
2.862
−39.187
1.00
14.77
A


ATOM
1061
CA
ARG
A
209
15.473
1.686
−40.041
1.00
14.78
A


ATOM
1062
CB
ARG
A
209
14.910
1.999
−41.434
1.00
16.76
A


ATOM
1063
CG
ARG
A
209
14.841
0.804
−42.360
1.00
18.33
A


ATOM
1064
CD
ARG
A
209
14.418
−0.437
−41.596
1.00
22.27
A


ATOM
1065
NE
ARG
A
209
13.889
−1.463
−42.480
1.00
25.66
A


ATOM
1066
CZ
ARG
A
209
12.611
−1.556
−42.834
1.00
28.46
A


ATOM
1067
NH1
ARG
A
209
11.709
−0.687
−42.377
1.00
27.84
A


ATOM
1068
NH2
ARG
A
209
12.235
−2.516
−43.659
1.00
28.08
A


ATOM
1069
C
ARG
A
209
16.934
1.210
−40.145
1.00
14.81
A


ATOM
1070
O
ARG
A
209
17.224
0.025
−40.001
1.00
12.46
A


ATOM
1071
N
ILE
A
210
17.854
2.137
−40.389
1.00
13.90
A


ATOM
1072
CA
ILE
A
210
19.261
1.774
−40.482
1.00
13.38
A


ATOM
1073
CB
ILE
A
210
20.138
3.010
−40.830
1.00
14.75
A


ATOM
1074
CG2
ILE
A
210
21.620
2.649
−40.768
1.00
13.71
A


ATOM
1075
CG1
ILE
A
210
19.775
3.526
−42.229
1.00
12.89
A


ATOM
1076
CD1
ILE
A
210
20.449
4.828
−42.600
1.00
11.08
A


ATOM
1077
C
ILE
A
210
19.709
1.200
−39.140
1.00
14.16
A


ATOM
1078
O
ILE
A
210
20.444
0.210
−39.092
1.00
12.22
A


ATOM
1079
N
PHE
A
211
19.247
1.816
−38.050
1.00
13.33
A


ATOM
1080
CA
PHE
A
211
19.622
1.358
−36.718
1.00
13.42
A


ATOM
1081
CB
PHE
A
211
18.978
2.221
−35.634
1.00
13.55
A


ATOM
1082
CG
PHE
A
211
19.137
1.642
−34.261
1.00
10.76
A


ATOM
1083
CD1
PHE
A
211
20.323
1.815
−33.555
1.00
10.51
A


ATOM
1084
CD2
PHE
A
211
18.145
0.827
−33.719
1.00
11.87
A


ATOM
1085
CE1
PHE
A
211
20.522
1.175
−32.328
1.00
11.75
A


ATOM
1086
CE2
PHE
A
211
18.338
0.179
−32.489
1.00
9.24
A


ATOM
1087
CZ
PHE
A
211
19.527
0.355
−31.797
1.00
8.29
A


ATOM
1088
C
PHE
A
211
19.275
−0.107
−36.421
1.00
13.34
A


ATOM
1089
O
PHE
A
211
20.108
−0.863
−35.901
1.00
12.59
A


ATOM
1090
N
GLN
A
212
18.039
−0.495
−36.721
1.00
11.92
A


ATOM
1091
CA
GLN
A
212
17.590
−1.860
−36.468
1.00
13.18
A


ATOM
1092
CB
GLN
A
212
16.084
−1.968
−36.702
1.00
12.41
A


ATOM
1093
CG
GLN
A
212
15.287
−1.129
−35.730
1.00
14.52
A


ATOM
1094
CD
GLN
A
212
13.820
−1.126
−36.049
1.00
16.44
A


ATOM
1095
OE1
GLN
A
212
13.102
−2.070
−35.732
1.00
18.15
A


ATOM
1096
NE2
GLN
A
212
13.362
−0.067
−36.698
1.00
17.06
A


ATOM
1097
C
GLN
A
212
18.341
−2.887
−37.313
1.00
13.31
A


ATOM
1098
O
GLN
A
212
18.689
−3.976
−36.823
1.00
12.33
A


ATOM
1099
N
HIS
A
213
18.584
−2.543
−38.574
1.00
12.02
A


ATOM
1100
CA
HIS
A
213
19.326
−3.421
−39.470
1.00
13.70
A


ATOM
1101
CB
HIS
A
213
19.485
−2.754
−40.845
1.00
15.78
A


ATOM
1102
CG
HIS
A
213
20.385
−3.497
−41.785
1.00
16.70
A


ATOM
1103
CD2
HIS
A
213
21.733
−3.494
−41.917
1.00
18.08
A


ATOM
1104
ND1
HIS
A
213
19.914
−4.410
−42.704
1.00
19.47
A


ATOM
1105
CE1
HIS
A
213
20.932
−4.939
−43.361
1.00
18.40
A


ATOM
1106
NE2
HIS
A
213
22.047
−4.401
−42.901
1.00
18.23
A


ATOM
1107
C
HIS
A
213
20.712
−3.679
−38.856
1.00
13.57
A


ATOM
1108
O
HIS
A
213
21.184
−4.822
−38.832
1.00
13.81
A


ATOM
1109
N
GLU
A
214
21.347
−2.621
−38.346
1.00
11.88
A


ATOM
1110
CA
GLU
A
214
22.686
−2.741
−37.750
1.00
13.61
A


ATOM
1111
CB
GLU
A
214
23.372
−1.374
−37.656
1.00
13.71
A


ATOM
1112
CG
GLU
A
214
23.547
−0.614
−38.972
1.00
14.63
A


ATOM
1113
CD
GLU
A
214
24.277
−1.403
−40.055
1.00
17.21
A


ATOM
1114
OE1
GLU
A
214
25.122
−2.266
−39.730
1.00
15.04
A


ATOM
1115
OE2
GLU
A
214
24.015
−1.132
−41.250
1.00
21.39
A


ATOM
1116
C
GLU
A
214
22.671
−3.376
−36.361
1.00
14.65
A


ATOM
1117
O
GLU
A
214
23.628
−4.041
−35.957
1.00
14.69
A


ATOM
1118
N
TYR
A
215
21.594
−3.155
−35.620
1.00
16.18
A


ATOM
1119
CA
TYR
A
215
21.488
−3.742
−34.298
1.00
15.85
A


ATOM
1120
CB
TYR
A
215
20.218
−3.261
−33.587
1.00
17.67
A


ATOM
1121
CG
TYR
A
215
20.067
−3.844
−32.196
1.00
21.32
A


ATOM
1122
CD1
TYR
A
215
20.887
−3.421
−31.148
1.00
19.48
A


ATOM
1123
CE1
TYR
A
215
20.798
−4.003
−29.883
1.00
20.09
A


ATOM
1124
CD2
TYR
A
215
19.143
−4.866
−31.940
1.00
20.98
A


ATOM
1125
CE2
TYR
A
215
19.046
−5.452
−30.680
1.00
20.75
A


ATOM
1126
CZ
TYR
A
215
19.879
−5.020
−29.654
1.00
21.44
A


ATOM
1127
OH
TYR
A
215
19.821
−5.626
−28.413
1.00
18.89
A


ATOM
1128
C
TYR
A
215
21.452
−5.260
−34.472
1.00
14.58
A


ATOM
1129
O
TYR
A
215
22.055
−6.007
−33.689
1.00
14.06
A


ATOM
1130
N
ASP
A
216
20.750
−5.710
−35.506
1.00
13.46
A


ATOM
1131
CA
ASP
A
216
20.657
−7.135
−35.787
1.00
14.06
A


ATOM
1132
CB
ASP
A
216
19.780
−7.388
−37.008
1.00
13.61
A


ATOM
1133
CG
ASP
A
216
18.308
−7.427
−36.671
1.00
13.64
A


ATOM
1134
OD1
ASP
A
216
17.957
−7.402
−35.475
1.00
12.49
A


ATOM
1135
OD2
ASP
A
216
17.495
−7.489
−37.611
1.00
15.97
A


ATOM
1136
C
ASP
A
216
22.041
−7.720
−36.031
1.00
15.02
A


ATOM
1137
O
ASP
A
216
22.353
−8.823
−35.557
1.00
16.95
A


ATOM
1138
N
HIS
A
217
22.863
−6.988
−36.779
1.00
13.44
A


ATOM
1139
CA
HIS
A
217
24.218
−7.433
−37.065
1.00
13.38
A


ATOM
1140
CB
HIS
A
217
25.011
−6.350
−37.810
1.00
13.13
A


ATOM
1141
CG
HIS
A
217
24.825
−6.370
−39.293
1.00
14.65
A


ATOM
1142
CD2
HIS
A
217
24.458
−5.397
−40.160
1.00
16.14
A


ATOM
1143
ND1
HIS
A
217
25.054
−7.495
−40.056
1.00
14.89
A


ATOM
1144
CE1
HIS
A
217
24.836
−7.214
−41.328
1.00
14.42
A


ATOM
1145
NE2
HIS
A
217
24.473
−5.948
−41.418
1.00
17.14
A


ATOM
1146
C
HIS
A
217
24.906
−7.717
−35.736
1.00
14.40
A


ATOM
1147
O
HIS
A
217
25.659
−8.684
−35.604
1.00
12.69
A


ATOM
1148
N
LEU
A
218
24.644
−6.864
−34.750
1.00
14.83
A


ATOM
1149
CA
LEU
A
218
25.255
−7.037
−33.445
1.00
14.51
A


ATOM
1150
CB
LEU
A
218
25.053
−5.766
−32.611
1.00
12.54
A


ATOM
1151
CG
LEU
A
218
25.713
−4.539
−33.285
1.00
17.61
A


ATOM
1152
CD1
LEU
A
218
25.643
−3.309
−32.390
1.00
16.94
A


ATOM
1153
CD2
LEU
A
218
27.180
−4.856
−33.619
1.00
14.59
A


ATOM
1154
C
LEU
A
218
24.727
−8.291
−32.741
1.00
15.91
A


ATOM
1155
O
LEU
A
218
25.375
−8.827
−31.846
1.00
17.34
A


ATOM
1156
N
GLU
A
219
23.564
−8.774
−33.164
1.00
15.63
A


ATOM
1157
CA
GLU
A
219
22.994
−9.983
−32.586
1.00
18.38
A


ATOM
1158
CB
GLU
A
219
21.467
−9.865
−32.462
1.00
22.20
A


ATOM
1159
CG
GLU
A
219
20.962
−8.892
−31.401
1.00
27.10
A


ATOM
1160
CD
GLU
A
219
21.262
−9.346
−29.987
1.00
30.86
A


ATOM
1161
OE1
GLU
A
219
21.025
−10.535
−29.673
1.00
33.62
A


ATOM
1162
OE2
GLU
A
219
21.723
−8.510
−29.183
1.00
34.35
A


ATOM
1163
C
GLU
A
219
23.327
−11.184
−33.477
1.00
17.11
A


ATOM
1164
O
GLU
A
219
22.786
−12.272
−33.283
1.00
17.19
A


ATOM
1165
N
GLY
A
220
24.220
−10.983
−34.444
1.00
14.72
A


ATOM
1166
CA
GLY
A
220
24.580
−12.056
−35.356
1.00
12.31
A


ATOM
1167
C
GLY
A
220
23.423
−12.355
−36.302
1.00
15.10
A


ATOM
1168
O
GLY
A
220
23.401
−13.389
−36.979
1.00
14.67
A


ATOM
1169
N
VAL
A
221
22.456
−11.437
−36.347
1.00
14.21
A


ATOM
1170
CA
VAL
A
221
21.278
−11.581
−37.191
1.00
14.18
A


ATOM
1171
CB
VAL
A
221
20.023
−11.047
−36.462
1.00
17.59
A


ATOM
1172
CG1
VAL
A
221
18.802
−11.120
−37.377
1.00
17.23
A


ATOM
1173
CG2
VAL
A
221
19.791
−11.844
−35.182
1.00
15.15
A


ATOM
1174
C
VAL
A
221
21.418
−10.848
−38.529
1.00
14.45
A


ATOM
1175
O
VAL
A
221
21.732
−9.657
−38.568
1.00
11.29
A


ATOM
1176
N
LEU
A
222
21.176
−11.571
−39.620
1.00
13.92
A


ATOM
1177
CA
LEU
A
222
21.269
−11.004
−40.965
1.00
15.74
A


ATOM
1178
CB
LEU
A
222
21.972
−12.000
−41.893
1.00
13.26
A


ATOM
1179
CG
LEU
A
222
23.492
−11.841
−42.001
1.00
13.73
A


ATOM
1180
CD1
LEU
A
222
24.070
−11.302
−40.699
1.00
13.62
A


ATOM
1181
CD2
LEU
A
222
24.119
−13.182
−42.379
1.00
12.93
A


ATOM
1182
C
LEU
A
222
19.886
−10.639
−41.496
1.00
15.93
A


ATOM
1183
O
LEU
A
222
18.906
−11.326
−41.198
1.00
16.25
A


ATOM
1184
N
PHE
A
223
19.811
−9.579
−42.302
1.00
17.16
A


ATOM
1185
CA
PHE
A
223
18.529
−9.097
−42.815
1.00
15.87
A


ATOM
1186
CB
PHE
A
223
18.722
−7.817
−43.661
1.00
17.74
A


ATOM
1187
CG
PHE
A
223
19.229
−8.044
−45.073
1.00
18.05
A


ATOM
1188
CD1
PHE
A
223
20.177
−9.023
−45.361
1.00
19.74
A


ATOM
1189
CD2
PHE
A
223
18.803
−7.207
−46.109
1.00
18.79
A


ATOM
1190
CE1
PHE
A
223
20.694
−9.161
−46.658
1.00
17.18
A


ATOM
1191
CE2
PHE
A
223
19.312
−7.333
−47.407
1.00
14.65
A


ATOM
1192
CZ
PHE
A
223
20.259
−8.311
−47.680
1.00
18.55
A


ATOM
1193
C
PHE
A
223
17.635
−10.089
−43.539
1.00
17.30
A


ATOM
1194
O
PHE
A
223
16.408
−9.948
−43.493
1.00
16.29
A


ATOM
1195
N
PHE
A
224
18.207
−11.103
−44.187
1.00
16.43
A


ATOM
1196
CA
PHE
A
224
17.341
−12.058
−44.861
1.00
15.78
A


ATOM
1197
CB
PHE
A
224
18.116
−12.898
−45.906
1.00
14.49
A


ATOM
1198
CG
PHE
A
224
19.045
−13.945
−45.331
1.00
12.96
A


ATOM
1199
CD1
PHE
A
224
18.548
−15.152
−44.854
1.00
11.77
A


ATOM
1200
CD2
PHE
A
224
20.430
−13.742
−45.334
1.00
12.30
A


ATOM
1201
CE1
PHE
A
224
19.421
−16.150
−44.392
1.00
12.19
A


ATOM
1202
CE2
PHE
A
224
21.314
−14.720
−44.877
1.00
7.51
A


ATOM
1203
CZ
PHE
A
224
20.812
−15.930
−44.405
1.00
13.32
A


ATOM
1204
C
PHE
A
224
16.636
−12.923
−43.818
1.00
17.87
A


ATOM
1205
O
PHE
A
224
15.608
−13.541
−44.115
1.00
16.51
A


ATOM
1206
N
ASP
A
225
17.175
−12.930
−42.592
1.00
17.97
A


ATOM
1207
CA
ASP
A
225
16.586
−13.692
−41.484
1.00
17.66
A


ATOM
1208
CB
ASP
A
225
17.426
−13.586
−40.186
1.00
16.43
A


ATOM
1209
CG
ASP
A
225
18.781
−14.305
−40.260
1.00
18.04
A


ATOM
1210
OD1
ASP
A
225
18.941
−15.266
−41.040
1.00
16.53
A


ATOM
1211
OD2
ASP
A
225
19.697
−13.911
−39.504
1.00
17.05
A


ATOM
1212
C
ASP
A
225
15.182
−13.151
−41.163
1.00
18.56
A


ATOM
1213
O
ASP
A
225
14.311
−13.894
−40.713
1.00
18.42
A


ATOM
1214
N
ARG
A
226
14.969
−11.858
−41.386
1.00
18.50
A


ATOM
1215
CA
ARG
A
226
13.681
−11.240
−41.072
1.00
21.41
A


ATOM
1216
CB
ARG
A
226
13.915
−9.901
−40.360
1.00
22.31
A


ATOM
1217
CG
ARG
A
226
14.890
−10.019
−39.186
1.00
25.19
A


ATOM
1218
CD
ARG
A
226
15.206
−8.683
−38.564
1.00
28.37
A


ATOM
1219
NE
ARG
A
226
14.317
−8.367
−37.451
1.00
32.73
A


ATOM
1220
CZ
ARG
A
226
14.361
−8.965
−36.264
1.00
35.61
A


ATOM
1221
NH1
ARG
A
226
15.258
−9.916
−36.031
1.00
38.22
A


ATOM
1222
NH2
ARG
A
226
13.503
−8.621
−35.310
1.00
35.12
A


ATOM
1223
C
ARG
A
226
12.758
−11.044
−42.279
1.00
21.52
A


ATOM
1224
O
ARG
A
226
11.689
−10.447
−42.165
1.00
21.42
A


ATOM
1225
N
MET
A
227
13.166
−11.559
−43.433
1.00
20.50
A


ATOM
1226
CA
MET
A
227
12.345
−11.432
−44.628
1.00
20.39
A


ATOM
1227
CB
MET
A
227
13.202
−11.585
−45.884
1.00
18.95
A


ATOM
1228
CG
MET
A
227
14.359
−10.619
−45.971
1.00
18.23
A


ATOM
1229
SD
MET
A
227
15.261
−10.828
−47.512
1.00
16.76
A


ATOM
1230
CE
MET
A
227
16.117
−9.282
−47.571
1.00
16.68
A


ATOM
1231
C
MET
A
227
11.275
−12.515
−44.620
1.00
19.32
A


ATOM
1232
O
MET
A
227
11.432
−13.547
−43.969
1.00
17.02
A


ATOM
1233
N
THR
A
228
10.180
−12.271
−45.324
1.00
19.28
A


ATOM
1234
CA
THR
A
228
9.129
−13.269
−45.401
1.00
23.61
A


ATOM
1235
CB
THR
A
228
7.854
−12.705
−46.062
1.00
23.79
A


ATOM
1236
OG1
THR
A
228
8.189
−12.120
−47.327
1.00
22.17
A


ATOM
1237
CG2
THR
A
228
7.213
−11.645
−45.165
1.00
20.55
A


ATOM
1238
C
THR
A
228
9.671
−14.415
−46.247
1.00
26.65
A


ATOM
1239
O
THR
A
228
10.715
−14.282
−46.899
1.00
25.82
A


ATOM
1240
N
ASP
A
229
8.977
−15.544
−46.232
1.00
29.30
A


ATOM
1241
CA
ASP
A
229
9.418
−16.689
−47.014
1.00
32.65
A


ATOM
1242
CB
ASP
A
229
8.494
−17.890
−46.756
1.00
38.87
A


ATOM
1243
CG
ASP
A
229
8.284
−18.172
−45.259
1.00
45.09
A


ATOM
1244
OD1
ASP
A
229
7.796
−17.274
−44.534
1.00
48.75
A


ATOM
1245
OD2
ASP
A
229
8.600
−19.298
−44.806
1.00
45.52
A


ATOM
1246
C
ASP
A
229
9.401
−16.310
−48.503
1.00
32.03
A


ATOM
1247
O
ASP
A
229
10.309
−16.660
−49.258
1.00
31.02
A


ATOM
1248
N
GLN
A
230
8.374
−15.572
−48.913
1.00
31.00
A


ATOM
1249
CA
GLN
A
230
8.238
−15.162
−50.305
1.00
31.22
A


ATOM
1250
CB
GLN
A
230
6.884
−14.487
−50.533
1.00
32.85
A


ATOM
1251
CG
GLN
A
230
5.709
−15.456
−50.531
1.00
37.00
A


ATOM
1252
CD
GLN
A
230
4.364
−14.754
−50.639
1.00
38.18
A


ATOM
1253
OE1
GLN
A
230
4.100
−14.024
−51.601
1.00
38.74
A


ATOM
1254
NE2
GLN
A
230
3.502
−14.976
−49.650
1.00
37.86
A


ATOM
1255
C
GLN
A
230
9.348
−14.243
−50.787
1.00
29.78
A


ATOM
1256
O
GLN
A
230
9.902
−14.453
−51.869
1.00
29.39
A


ATOM
1257
N
VAL
A
231
9.665
−13.217
−50.005
1.00
27.08
A


ATOM
1258
CA
VAL
A
231
10.726
−12.303
−50.401
1.00
26.16
A


ATOM
1259
CB
VAL
A
231
10.801
−11.080
−49.469
1.00
26.30
A


ATOM
1260
CG1
VAL
A
231
9.551
−10.231
−49.610
1.00
25.48
A


ATOM
1261
CG2
VAL
A
231
10.936
−11.536
−48.055
1.00
27.95
A


ATOM
1262
C
VAL
A
231
12.050
−13.056
−50.371
1.00
25.45
A


ATOM
1263
O
VAL
A
231
12.949
−12.789
−51.172
1.00
25.65
A


ATOM
1264
N
LEU
A
232
12.162
−14.014
−49.456
1.00
24.04
A


ATOM
1265
CA
LEU
A
232
13.379
−14.804
−49.345
1.00
22.95
A


ATOM
1266
CB
LEU
A
232
13.304
−15.753
−48.148
1.00
23.20
A


ATOM
1267
CG
LEU
A
232
14.562
−16.605
−47.940
1.00
24.20
A


ATOM
1268
CD1
LEU
A
232
15.782
−15.692
−47.782
1.00
25.17
A


ATOM
1269
CD2
LEU
A
232
14.390
−17.490
−46.718
1.00
25.41
A


ATOM
1270
C
LEU
A
232
13.614
−15.606
−50.621
1.00
24.32
A


ATOM
1271
O
LEU
A
232
14.745
−15.687
−51.113
1.00
23.37
A


ATOM
1272
N
ASP
A
233
12.554
−16.206
−51.156
1.00
24.48
A


ATOM
1273
CA
ASP
A
233
12.688
−16.974
−52.386
1.00
25.90
A


ATOM
1274
CB
ASP
A
233
11.348
−17.582
−52.826
1.00
27.95
A


ATOM
1275
CG
ASP
A
233
10.871
−18.694
−51.902
1.00
31.23
A


ATOM
1276
OD1
ASP
A
233
11.721
−19.352
−51.261
1.00
31.77
A


ATOM
1277
OD2
ASP
A
233
9.642
−18.922
−51.831
1.00
33.39
A


ATOM
1278
C
ASP
A
233
13.209
−16.065
−53.490
1.00
24.49
A


ATOM
1279
O
ASP
A
233
14.045
−16.477
−54.288
1.00
23.31
A


ATOM
1280
N
SER
A
234
12.728
−14.822
−53.519
1.00
23.93
A


ATOM
1281
CA
SER
A
234
13.144
−13.867
−54.546
1.00
24.19
A


ATOM
1282
CB
SER
A
234
12.434
−12.522
−54.357
1.00
24.54
A


ATOM
1283
OG
SER
A
234
13.044
−11.745
−53.341
1.00
26.38
A


ATOM
1284
C
SER
A
234
14.655
−13.624
−54.609
1.00
24.31
A


ATOM
1285
O
SER
A
234
15.154
−13.082
−55.591
1.00
26.53
A


ATOM
1286
N
ILE
A
235
15.388
−14.006
−53.570
1.00
23.33
A


ATOM
1287
CA
ILE
A
235
16.830
−13.808
−53.596
1.00
21.51
A


ATOM
1288
CB
ILE
A
235
17.262
−12.641
−52.663
1.00
20.78
A


ATOM
1289
CG2
ILE
A
235
16.624
−11.329
−53.138
1.00
14.94
A


ATOM
1290
CG1
ILE
A
235
16.879
−12.964
−51.216
1.00
18.91
A


ATOM
1291
CD1
ILE
A
235
17.392
−11.968
−50.211
1.00
18.32
A


ATOM
1292
C
ILE
A
235
17.616
−15.061
−53.215
1.00
22.26
A


ATOM
1293
O
ILE
A
235
18.810
−14.983
−52.919
1.00
22.63
A


ATOM
1294
N
ARG
A
236
16.958
−16.217
−53.229
1.00
22.15
A


ATOM
1295
CA
ARG
A
236
17.637
−17.459
−52.882
1.00
23.00
A


ATOM
1296
CB
ARG
A
236
16.685
−18.648
−53.003
1.00
24.18
A


ATOM
1297
CG
ARG
A
236
15.802
−18.852
−51.786
1.00
28.66
A


ATOM
1298
CD
ARG
A
236
14.937
−20.104
−51.903
1.00
30.02
A


ATOM
1299
NE
ARG
A
236
14.181
−20.349
−50.678
1.00
31.89
A


ATOM
1300
CZ
ARG
A
236
14.710
−20.823
−49.552
1.00
33.51
A


ATOM
1301
NH1
ARG
A
236
16.003
−21.115
−49.490
1.00
33.19
A


ATOM
1302
NH2
ARG
A
236
13.947
−20.989
−48.480
1.00
35.80
A


ATOM
1303
C
ARG
A
236
18.865
−17.704
−53.758
1.00
24.86
A


ATOM
1304
O
ARG
A
236
19.946
−18.026
−53.248
1.00
24.45
A


ATOM
1305
N
GLU
A
237
18.698
−17.556
−55.073
1.00
23.40
A


ATOM
1306
CA
GLU
A
237
19.802
−17.775
−55.996
1.00
22.38
A


ATOM
1307
CB
GLU
A
237
19.339
−17.613
−57.450
1.00
21.86
A


ATOM
1308
CG
GLU
A
237
18.187
−18.534
−57.832
1.00
26.01
A


ATOM
1309
CD
GLU
A
237
18.347
−19.954
−57.284
1.00
28.79
A


ATOM
1310
OE1
GLU
A
237
19.326
−20.640
−57.649
1.00
31.36
A


ATOM
1311
OE2
GLU
A
237
17.487
−20.387
−56.479
1.00
31.54
A


ATOM
1312
C
GLU
A
237
20.931
−16.803
−55.683
1.00
19.80
A


ATOM
1313
O
GLU
A
237
22.102
−17.174
−55.709
1.00
18.95
A


ATOM
1314
N
GLU
A
238
20.570
−15.567
−55.362
1.00
17.58
A


ATOM
1315
CA
GLU
A
238
21.557
−14.546
−55.035
1.00
16.50
A


ATOM
1316
CB
GLU
A
238
20.848
−13.219
−54.729
1.00
16.60
A


ATOM
1317
CG
GLU
A
238
20.357
−12.449
−55.972
1.00
15.75
A


ATOM
1318
CD
GLU
A
238
19.198
−13.120
−56.712
1.00
16.05
A


ATOM
1319
OE1
GLU
A
238
18.860
−12.653
−57.817
1.00
15.84
A


ATOM
1320
OE2
GLU
A
238
18.613
−14.097
−56.199
1.00
19.07
A


ATOM
1321
C
GLU
A
238
22.449
−14.961
−53.851
1.00
16.83
A


ATOM
1322
O
GLU
A
238
23.677
−14.877
−53.925
1.00
14.90
A


ATOM
1323
N
LEU
A
239
21.820
−15.405
−52.764
1.00
15.47
A


ATOM
1324
CA
LEU
A
239
22.542
−15.836
−51.574
1.00
16.39
A


ATOM
1325
CB
LEU
A
239
21.553
−16.095
−50.428
1.00
14.91
A


ATOM
1326
CG
LEU
A
239
20.700
−14.891
−50.006
1.00
17.17
A


ATOM
1327
CD1
LEU
A
239
19.828
−15.234
−48.796
1.00
15.12
A


ATOM
1328
CD2
LEU
A
239
21.617
−13.734
−49.679
1.00
15.57
A


ATOM
1329
C
LEU
A
239
23.344
−17.100
−51.874
1.00
16.05
A


ATOM
1330
O
LEU
A
239
24.430
−17.316
−51.331
1.00
14.99
A


ATOM
1331
N
GLU
A
240
22.800
−17.927
−52.756
1.00
17.95
A


ATOM
1332
CA
GLU
A
240
23.444
−19.169
−53.149
1.00
21.35
A


ATOM
1333
CB
GLU
A
240
22.492
−19.969
−54.037
1.00
25.83
A


ATOM
1334
CG
GLU
A
240
22.635
−21.471
−53.966
1.00
31.74
A


ATOM
1335
CD
GLU
A
240
21.535
−22.176
−54.753
1.00
36.90
A


ATOM
1336
OE1
GLU
A
240
20.349
−21.810
−54.566
1.00
37.59
A


ATOM
1337
OE2
GLU
A
240
21.853
−23.092
−55.549
1.00
39.47
A


ATOM
1338
C
GLU
A
240
24.740
−18.854
−53.903
1.00
19.90
A


ATOM
1339
O
GLU
A
240
25.748
−19.548
−53.743
1.00
20.76
A


ATOM
1340
N
ALA
A
241
24.711
−17.798
−54.710
1.00
18.49
A


ATOM
1341
CA
ALA
A
241
25.887
−17.396
−55.480
1.00
18.34
A


ATOM
1342
CB
ALA
A
241
25.515
−16.306
−56.483
1.00
19.10
A


ATOM
1343
C
ALA
A
241
27.007
−16.905
−54.566
1.00
17.84
A


ATOM
1344
O
ALA
A
241
28.183
−17.073
−54.881
1.00
17.32
A


ATOM
1345
N
LEU
A
242
26.642
−16.289
−53.441
1.00
17.42
A


ATOM
1346
CA
LEU
A
242
27.641
−15.794
−52.494
1.00
17.40
A


ATOM
1347
CB
LEU
A
242
27.005
−14.800
−51.517
1.00
14.72
A


ATOM
1348
CG
LEU
A
242
26.611
−13.447
−52.119
1.00
13.60
A


ATOM
1349
CD1
LEU
A
242
25.823
−12.653
−51.105
1.00
13.80
A


ATOM
1350
CD2
LEU
A
242
27.848
−12.675
−52.532
1.00
10.81
A


ATOM
1351
C
LEU
A
242
28.267
−16.965
−51.730
1.00
18.23
A


ATOM
1352
O
LEU
A
242
29.445
−16.925
−51.375
1.00
16.99
A


ATOM
1353
N
GLU
A
243
27.472
−18.007
−51.494
1.00
19.15
A


ATOM
1354
CA
GLU
A
243
27.941
−19.197
−50.792
1.00
20.79
A


ATOM
1355
CB
GLU
A
243
26.770
−20.140
−50.507
1.00
21.06
A


ATOM
1356
CG
GLU
A
243
25.848
−19.685
−49.378
1.00
19.76
A


ATOM
1357
CD
GLU
A
243
24.475
−20.318
−49.474
1.00
20.44
A


ATOM
1358
OE1
GLU
A
243
24.357
−21.358
−50.150
1.00
22.37
A


ATOM
1359
OE2
GLU
A
243
23.518
−19.784
−48.873
1.00
20.73
A


ATOM
1360
C
GLU
A
243
28.975
−19.912
−51.649
1.00
22.94
A


ATOM
1361
O
GLU
A
243
29.983
−20.410
−51.143
1.00
22.58
A


ATOM
1362
N
LYS
A
244
28.717
−19.963
−52.951
1.00
23.02
A


ATOM
1363
CA
LYS
A
244
29.637
−20.601
−53.879
1.00
24.52
A


ATOM
1364
CB
LYS
A
244
28.966
−20.798
−55.242
1.00
25.82
A


ATOM
1365
CG
LYS
A
244
27.699
−21.650
−55.171
1.00
31.89
A


ATOM
1366
CD
LYS
A
244
27.998
−23.064
−54.652
1.00
34.68
A


ATOM
1367
CE
LYS
A
244
26.751
−23.745
−54.097
1.00
35.93
A


ATOM
1368
NZ
LYS
A
244
26.233
−23.064
−52.871
1.00
36.31
A


ATOM
1369
C
LYS
A
244
30.884
−19.735
−54.024
1.00
24.80
A


ATOM
1370
O
LYS
A
244
32.005
−20.239
−53.979
1.00
24.15
A


ATOM
1371
N
LYS
A
245
30.686
−18.431
−54.194
1.00
23.61
A


ATOM
1372
CA
LYS
A
245
31.805
−17.503
−54.330
1.00
23.86
A


ATOM
1373
CB
LYS
A
245
31.276
−16.075
−54.482
1.00
24.85
A


ATOM
1374
CG
LYS
A
245
32.325
−14.977
−54.377
1.00
27.82
A


ATOM
1375
CD
LYS
A
245
33.472
−15.174
−55.357
1.00
30.16
A


ATOM
1376
CE
LYS
A
245
33.044
−14.966
−56.803
1.00
32.00
A


ATOM
1377
NZ
LYS
A
245
34.179
−15.225
−57.737
1.00
29.90
A


ATOM
1378
C
LYS
A
245
32.715
−17.609
−53.105
1.00
23.77
A


ATOM
1379
O
LYS
A
245
33.938
−17.506
−53.207
1.00
21.14
A


ATOM
1380
N
TYR
A
246
32.098
−17.827
−51.949
1.00
23.97
A


ATOM
1381
CA
TYR
A
246
32.823
−17.966
−50.694
1.00
23.96
A


ATOM
1382
CB
TYR
A
246
31.845
−18.110
−49.531
1.00
23.71
A


ATOM
1383
CG
TYR
A
246
32.520
−18.412
−48.219
1.00
24.55
A


ATOM
1384
CD1
TYR
A
246
33.192
−17.415
−47.518
1.00
23.26
A


ATOM
1385
CE1
TYR
A
246
33.847
−17.697
−46.323
1.00
23.72
A


ATOM
1386
CD2
TYR
A
246
32.517
−19.705
−47.692
1.00
25.41
A


ATOM
1387
CE2
TYR
A
246
33.172
−19.998
−46.497
1.00
24.58
A


ATOM
1388
CZ
TYR
A
246
33.835
−18.986
−45.821
1.00
24.76
A


ATOM
1389
OH
TYR
A
246
34.501
−19.257
−44.647
1.00
25.79
A


ATOM
1390
C
TYR
A
246
33.688
−19.210
−50.751
1.00
24.29
A


ATOM
1391
O
TYR
A
246
34.864
−19.187
−50.386
1.00
23.22
A


ATOM
1392
N
GLU
A
247
33.077
−20.302
−51.193
1.00
24.70
A


ATOM
1393
CA
GLU
A
247
33.767
−21.569
−51.302
1.00
26.80
A


ATOM
1394
CB
GLU
A
247
32.783
−22.658
−51.732
1.00
25.70
A


ATOM
1395
CG
GLU
A
247
31.852
−23.115
−50.617
1.00
26.11
A


ATOM
1396
CD
GLU
A
247
30.768
−24.069
−51.098
1.00
26.88
A


ATOM
1397
OE1
GLU
A
247
31.094
−25.045
−51.804
1.00
27.71
A


ATOM
1398
OE2
GLU
A
247
29.584
−23.848
−50.764
1.00
28.44
A


ATOM
1399
C
GLU
A
247
34.916
−21.461
−52.297
1.00
27.97
A


ATOM
1400
O
GLU
A
247
36.018
−21.937
−52.033
1.00
29.90
A


ATOM
1401
N
GLU
A
248
34.660
−20.816
−53.428
1.00
29.20
A


ATOM
1402
CA
GLU
A
248
35.675
−20.654
−54.460
1.00
31.97
A


ATOM
1403
CB
GLU
A
248
35.073
−20.025
−55.726
1.00
34.39
A


ATOM
1404
CG
GLU
A
248
35.868
−20.328
−57.004
1.00
40.86
A


ATOM
1405
CD
GLU
A
248
35.930
−19.154
−57.983
1.00
44.67
A


ATOM
1406
OE1
GLU
A
248
34.864
−18.578
−58.313
1.00
47.37
A


ATOM
1407
OE2
GLU
A
248
37.052
−18.813
−58.432
1.00
44.21
A


ATOM
1408
C
GLU
A
248
36.829
−19.780
−53.976
1.00
31.88
A


ATOM
1409
O
GLU
A
248
37.993
−20.072
−54.255
1.00
31.42
A


ATOM
1410
N
LYS
A
249
36.509
−18.708
−53.254
1.00
31.46
A


ATOM
1411
CA
LYS
A
249
37.546
−17.803
−52.769
1.00
31.64
A


ATOM
1412
CB
LYS
A
249
36.948
−16.456
−52.340
1.00
31.29
A


ATOM
1413
CG
LYS
A
249
37.985
−15.524
−51.731
1.00
33.88
A


ATOM
1414
CD
LYS
A
249
37.443
−14.145
−51.384
1.00
36.01
A


ATOM
1415
CE
LYS
A
249
38.546
−13.266
−50.777
1.00
38.28
A


ATOM
1416
NZ
LYS
A
249
38.102
−11.882
−50.419
1.00
39.36
A


ATOM
1417
C
LYS
A
249
38.372
−18.371
−51.618
1.00
31.30
A


ATOM
1418
O
LYS
A
249
39.598
−18.353
−51.672
1.00
31.00
A


ATOM
1419
N
THR
A
250
37.708
−18.877
−50.584
1.00
30.44
A


ATOM
1420
CA
THR
A
250
38.418
−19.414
−49.428
1.00
31.23
A


ATOM
1421
CB
THR
A
250
37.555
−19.338
−48.148
1.00
31.86
A


ATOM
1422
OG1
THR
A
250
36.507
−20.314
−48.214
1.00
34.34
A


ATOM
1423
CG2
THR
A
250
36.941
−17.952
−48.001
1.00
34.00
A


ATOM
1424
C
THR
A
250
38.892
−20.857
−49.586
1.00
30.95
A


ATOM
1425
O
THR
A
250
39.942
−21.223
−49.065
1.00
29.91
A


ATOM
1426
N
GLY
A
251
38.125
−21.668
−50.306
1.00
30.20
A


ATOM
1427
CA
GLY
A
251
38.491
−23.064
−50.475
1.00
30.06
A


ATOM
1428
C
GLY
A
251
37.843
−23.878
−49.365
1.00
30.74
A


ATOM
1429
O
GLY
A
251
38.060
−25.083
−49.238
1.00
31.77
A


ATOM
1430
N
LEU
A
252
37.030
−23.193
−48.564
1.00
29.90
A


ATOM
1431
CA
LEU
A
252
36.323
−23.790
−47.440
1.00
27.62
A


ATOM
1432
CB
LEU
A
252
36.561
−22.942
−46.191
1.00
27.01
A


ATOM
1433
CG
LEU
A
252
38.024
−22.633
−45.872
1.00
25.71
A


ATOM
1434
CD1
LEU
A
252
38.102
−21.489
−44.875
1.00
25.85
A


ATOM
1435
CD2
LEU
A
252
38.701
−23.888
−45.330
1.00
24.69
A


ATOM
1436
C
LEU
A
252
34.823
−23.840
−47.736
1.00
27.80
A


ATOM
1437
O
LEU
A
252
34.306
−23.006
−48.480
1.00
27.40
A


ATOM
1438
N
PRO
A
253
34.109
−24.822
−47.159
1.00
27.39
A


ATOM
1439
CD
PRO
A
253
34.659
−25.921
−46.355
1.00
27.81
A


ATOM
1440
CA
PRO
A
253
32.663
−24.994
−47.344
1.00
28.16
A


ATOM
1441
CB
PRO
A
253
32.399
−26.394
−46.784
1.00
28.26
A


ATOM
1442
CG
PRO
A
253
33.756
−27.045
−46.736
1.00
28.79
A


ATOM
1443
C
PRO
A
253
31.954
−23.931
−46.506
1.00
29.29
A


ATOM
1444
O
PRO
A
253
32.331
−23.707
−45.355
1.00
30.16
A


ATOM
1445
N
SER
A
254
30.931
−23.283
−47.054
1.00
30.59
A


ATOM
1446
CA
SER
A
254
30.231
−22.248
−46.286
1.00
32.13
A


ATOM
1447
CB
SER
A
254
29.629
−21.192
−47.219
1.00
31.94
A


ATOM
1448
OG
SER
A
254
28.478
−21.688
−47.880
1.00
30.37
A


ATOM
1449
C
SER
A
254
29.114
−22.815
−45.423
1.00
32.34
A


ATOM
1450
O
SER
A
254
28.543
−23.851
−45.742
1.00
30.85
A


ATOM
1451
N
PRO
A
255
28.808
−22.150
−44.299
1.00
34.62
A


ATOM
1452
CD
PRO
A
255
29.704
−21.193
−43.627
1.00
33.82
A


ATOM
1453
CA
PRO
A
255
27.736
−22.594
−43.393
1.00
35.62
A


ATOM
1454
CB
PRO
A
255
28.082
−21.906
−42.079
1.00
36.32
A


ATOM
1455
CG
PRO
A
255
29.590
−21.635
−42.200
1.00
35.07
A


ATOM
1456
C
PRO
A
255
26.410
−22.096
−43.984
1.00
38.43
A


ATOM
1457
O
PRO
A
255
25.564
−21.528
−43.295
1.00
37.08
A


ATOM
1458
N
GLU
A
256
26.273
−22.334
−45.287
1.00
42.39
A


ATOM
1459
CA
GLU
A
256
25.139
−21.942
−46.124
1.00
45.09
A


ATOM
1460
CB
GLU
A
256
25.419
−22.388
−47.564
1.00
48.71
A


ATOM
1461
CG
GLU
A
256
24.872
−23.776
−47.940
1.00
51.06
A


ATOM
1462
CD
GLU
A
256
25.525
−24.911
−47.177
1.00
54.43
A


ATOM
1463
OE1
GLU
A
256
26.723
−25.180
−47.422
1.00
54.78
A


ATOM
1464
OE2
GLU
A
256
24.840
−25.533
−46.334
1.00
54.37
A


ATOM
1465
C
GLU
A
256
23.721
−22.388
−45.759
1.00
45.88
A


ATOM
1466
O
GLU
A
256
23.420
−22.700
−44.607
1.00
46.95
A


ATOM
1467
N
ARG
A
257
22.875
−22.396
−46.795
1.00
47.40
A


ATOM
1468
CA
ARG
A
257
21.458
−22.766
−46.768
1.00
48.03
A


ATOM
1469
CB
ARG
A
257
21.166
−23.841
−45.708
1.00
49.00
A


ATOM
1470
CG
ARG
A
257
19.673
−24.239
−45.527
1.00
49.58
A


ATOM
1471
CD
ARG
A
257
18.926
−24.462
−46.845
1.00
50.25
A


ATOM
1472
NE
ARG
A
257
18.716
−23.197
−47.542
1.00
50.22
A


ATOM
1473
CZ
ARG
A
257
19.098
−22.961
−48.791
1.00
51.01
A


ATOM
1474
NH1
ARG
A
257
19.705
−23.913
−49.485
1.00
51.87
A


ATOM
1475
NH2
ARG
A
257
18.900
−21.767
−49.332
1.00
51.93
A


ATOM
1476
C
ARG
A
257
20.576
−21.545
−46.548
1.00
48.27
A


ATOM
1477
O
ARG
A
257
19.959
−21.445
−45.465
1.00
48.75
A


ATOM
1478
OXT
ARG
A
257
20.517
−20.700
−47.471
1.00
47.21
A


ATOM
1479
S
SO4
L
1
26.750
−1.543
−20.726
1.00
38.59
L


ATOM
1480
O1
SO4
L
1
26.466
−2.892
−21.261
1.00
36.34
L


ATOM
1481
O2
SO4
L
1
25.516
−0.950
−20.178
1.00
38.18
L


ATOM
1482
O3
SO4
L
1
27.748
−1.640
−19.643
1.00
39.55
L


ATOM
1483
O4
SO4
L
1
27.270
−0.687
−21.812
1.00
36.64
L


ATOM
1484
ZN + 2
ZN2
M
1
24.054
−4.948
−43.032
1.00
17.46
M


ATOM
1485
ZN + 2
ZN2
M
2
39.953
7.918
−41.358
1.00
25.22
M


ATOM
1486
ZN + 2
ZN2
M
3
36.946
−5.734
−22.999
1.00
22.38
M


ATOM
1487
ZN + 2
ZN2
M
4
19.157
−22.594
−56.610
0.50
43.08
M


ATOM
1488
ZN + 2
ZN2
M
5
21.794
−10.556
−27.675
0.40
29.27
M


ATOM
1489
ZN + 2
ZN2
M
6
−0.285
1.757
−30.184
0.50
36.10
M


ATOM
1490
OH2
TIP
S
1
25.969
−2.074
−44.807
1.00
14.25
S


ATOM
1491
OH2
TIP
S
2
3.811
2.346
−30.357
1.00
14.25
S


ATOM
1492
OH2
TIP
S
3
−0.051
0.258
−28.134
1.00
14.25
S


ATOM
1493
OH2
TIP
S
4
10.090
−8.668
−43.625
1.00
15.50
S


ATOM
1494
OH2
TIP
S
5
24.192
−17.873
−42.585
1.00
9.05
S


ATOM
1495
OH2
TIP
S
6
26.335
−9.687
−38.091
1.00
2.09
S


ATOM
1496
OH2
TIP
S
7
42.910
−1.393
−27.043
1.00
40.60
S


ATOM
1497
OH2
TIP
S
8
22.287
−8.014
−43.054
1.00
3.78
S


ATOM
1498
OH2
TIP
S
9
22.996
−4.825
−50.565
1.00
6.81
S


ATOM
1499
OH2
TIP
S
10
9.921
−9.608
−46.068
1.00
10.87
S


ATOM
1500
OH2
TIP
S
11
21.456
−25.782
−55.836
1.00
28.41
S


ATOM
1501
OH2
TIP
S
12
31.066
7.682
−53.311
1.00
21.03
S


ATOM
1502
OH2
TIP
S
13
11.349
−7.646
−52.115
1.00
13.10
S


ATOM
1503
OH2
TIP
S
14
24.496
−4.224
−28.092
1.00
23.20
S


ATOM
1504
OH2
TIP
S
15
20.931
−22.429
−58.425
1.00
14.25
S


ATOM
1505
OH2
TIP
S
16
27.530
−14.722
−42.923
1.00
9.87
S


ATOM
1506
OH2
TIP
S
17
9.342
6.275
−38.471
1.00
18.89
S


ATOM
1507
OH2
TIP
S
18
5.984
−3.364
−30.710
1.00
11.90
S


ATOM
1508
OH2
TIP
S
19
19.793
−0.210
−46.871
1.00
26.54
S


ATOM
1509
OH2
TIP
S
20
28.046
−17.680
−41.836
1.00
10.88
S


ATOM
1510
OH2
TIP
S
23
21.557
−7.309
−40.376
1.00
14.41
S


ATOM
1511
OH2
TIP
S
24
12.004
1.128
−39.615
1.00
16.43
S


ATOM
1512
OH2
TIP
S
25
30.777
−14.876
−50.134
1.00
11.00
S


ATOM
1513
OH2
TIP
S
26
−1.303
−0.882
−25.776
1.00
38.49
S


ATOM
1514
OH2
TIP
S
28
13.901
−4.350
−36.733
1.00
17.30
S


ATOM
1515
OH2
TIP
S
30
28.137
−11.377
−35.724
1.00
13.45
S


ATOM
1516
OH2
TIP
S
32
10.937
−8.045
−38.922
1.00
19.04
S


ATOM
1517
OH2
TIP
S
33
32.844
−9.803
−54.314
1.00
43.74
S


ATOM
1518
OH2
TIP
S
34
36.191
−3.234
−48.811
1.00
43.05
S


ATOM
1519
OH2
TIP
S
36
16.139
−16.545
−56.285
1.00
35.15
S


ATOM
1520
OH2
TIP
S
37
33.130
11.162
−16.863
1.00
27.08
S


ATOM
1521
OH2
TIP
S
38
13.131
−19.278
−54.777
1.00
21.83
S


ATOM
1522
OH2
TIP
S
39
26.597
−10.167
−54.360
1.00
17.41
S


ATOM
1523
OH2
TIP
S
40
12.308
−8.028
−32.094
1.00
23.20
S


ATOM
1524
OH2
TIP
S
41
23.225
−15.656
−35.045
1.00
28.13
S


ATOM
1525
OH2
TIP
S
42
24.923
−2.981
−42.626
1.00
13.51
S


ATOM
1526
OH2
TIP
S
43
44.298
−1.798
−33.197
1.00
17.76
S


ATOM
1527
OH2
TIP
S
44
20.680
−0.619
−44.292
1.00
14.01
S


ATOM
1528
OH2
TIP
S
45
5.896
−15.409
−44.351
1.00
22.87
S


ATOM
1529
OH2
TIP
S
46
23.233
−24.442
−53.915
1.00
39.19
S


ATOM
1530
OH2
TIP
S
47
14.208
−10.403
−32.245
1.00
18.95
S


ATOM
1531
OH2
TIP
S
48
38.832
−0.501
−27.020
1.00
14.49
S


ATOM
1532
OH2
TIP
S
49
18.236
−0.002
−44.579
1.00
27.51
S


ATOM
1533
OH2
TIP
S
50
36.434
8.748
−34.776
1.00
11.42
S


ATOM
1534
OH2
TIP
S
51
27.579
14.569
−38.647
1.00
28.40
S


ATOM
1535
OH2
TIP
S
52
38.153
2.185
−20.385
1.00
15.38
S


ATOM
1536
OH2
TIP
S
54
29.121
−17.432
−57.522
1.00
14.06
S


ATOM
1537
OH2
TIP
S
55
28.554
−19.346
−40.014
1.00
37.78
S


ATOM
1538
OH2
TIP
S
56
22.082
−22.880
−50.314
1.00
24.72
S


ATOM
1539
OH2
TIP
S
59
35.171
−10.112
−50.196
1.00
27.04
S


ATOM
1540
OH2
TIP
S
61
9.233
−20.875
−49.991
1.00
31.75
S


ATOM
1541
OH2
TIP
S
62
18.870
−7.844
−55.461
1.00
34.62
S


ATOM
1542
OH2
TIP
S
63
11.323
3.689
−39.850
1.00
18.17
S


ATOM
1543
OH2
TIP
S
64
35.403
9.921
−37.907
1.00
26.55
S


ATOM
1544
OH2
TIP
S
65
8.090
14.529
−43.710
1.00
30.17
S


ATOM
1545
OH2
TIP
S
66
38.045
−0.048
−19.192
1.00
30.52
S


ATOM
1546
OH2
TIP
S
67
33.352
−13.694
−29.289
1.00
33.68
S


ATOM
1547
OH2
TIP
S
69
35.976
−15.780
−40.760
1.00
13.56
S









The examples set forth above are provided to give those of ordinary skill in the art a complete disclosure and description of how to make and use the embodiments of the devices, systems and methods of the invention, and are not intended to limit the scope of what the inventors regard as their invention. Modifications of the above-described modes for carrying out the invention that are obvious to persons of skill in the art are intended to be within the scope of the following claims. All patents and publications mentioned in the specification are indicative of the levels of skill of those skilled in the art to which the invention pertains. All references cited in this disclosure are incorporated by reference to the same extent as if each reference had been incorporated by reference in its entirety individually.
In addition, it is understood that the terminology used herein is for the purpose of describing particular embodiments only, and is not intended to be limiting. As used in this specification and the appended claims, the singular forms “a,” “an,” and “the” include plural referents unless the content clearly dictates otherwise. Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which the invention pertains. Although any methods and materials similar or equivalent to those described herein can be used in the practice for testing of the invention(s), specific examples of appropriate materials and methods are described herein.
A number of embodiments of the invention have been described. Nevertheless, it will be understood that various modifications may be made without departing from the spirit and scope of the invention. Accordingly, other embodiments are within the scope of the following claims.

## Claims

1. A method of identifying a candidate compound that binds to the active site of Arabidopsis thaliana peptide deformylase polypeptide, the method comprising:
a) comparing, by a processor of a computer, the atomic structure of the compound with a three-dimensional structure of a crystalline form of an Arabidopsis thaliana peptide deformylase polypeptide, wherein the crystalline form of the polypeptide consists of the amino acid sequence of SEQ ID NO:1 complexed with Zn2+, wherein said crystalline form has the space group symmetry P41212; unit cell dimensions of a=about 49 angstroms to about 52 angstroms, b=about 49 angstroms to about 52 angstroms, and c=about 143 angstroms to about 147 angstroms; and alpha=beta=gamma=90 degrees; and
b) computationally identifying by the processor a candidate compound for an ability to bind to the Arabidopsis thaliana peptide deformylase
wherein said computer has the atomic coordinates of said polypeptide stored therein, and wherein said three-dimensional structure is generated from the structure coordinates of Table 1 or homologous structures coordinates for the amino acid residues of SEQ ID NO: 1 comprising a root mean square deviation of non-hydrogen atoms of less than about 0.35 Å when superimposed on the non-hydrogen atom positions of the corresponding atomic coordinates of Table 1.

2. The method of claim 1, wherein the candidate compound binds to the active site of the Arabidopsis thaliana peptide deformylase.

3. The method of claim 1, wherein the three-dimensional structure is generated from the structure coordinates for one or more Arabidopsis thaliana peptide deformylase amino acid residues Gly121, Gly123, Leu124, Gln128, Glu169, Gly170, Cys171, Leu172, His213, Glu214, His217, and Tyr178 according to Table 1, or similar structure coordinates for said amino acids comprising a root mean square deviation of non-hydrogen atoms of less than about 0.35 Å when superimposed on the non-hydrogen atom positions of the corresponding atomic coordinates of Table 1.

4. The method of claim 1, wherein the comparing comprises employing a computational means to perform a fitting operation between the compound and at least one binding site of the peptide deformylase.

5. The method of claim 1, further comprising synthesizing the candidate compound and screening the candidate compound for the ability to bind Arabidopsis thaliana peptide deformylase in vitro or in vivo.

6. The method of claim 5, wherein the compound is an herbicide.

7. A method of computationally designing a candidate compound that binds to Arabidopsis thaliana peptide deformylase polypeptide, the method comprising:
a) comparing by a processor of a computer the atomic structure of chemical entities, or fragments thereof, with a three-dimensional structural representation of a crystalline form of a polypeptide;
b) computationally identifying by the processor chemical entities capable of associating with the three-dimensional structural representation of a crystalline form of a polypeptide; and
c) assembling the chemical entities, or fragments thereof, into a single molecule to provide the structure of the candidate compound
wherein the crystalline form of the polypeptide consists of the amino acid sequence of SEQ ID NO:1 complexed with Zn2+, wherein said crystalline form has the space group symmetry P41212; unit cell dimensions of a=about 49 angstroms to about 52 angstroms, b=about 49 angstroms to about 52 angstroms, and c=about 143 angstroms to about 147 angstroms; and alpha=beta=gamma=90 degrees
wherein said computer has the atomic coordinates of said polypeptide stored therein.

8. The method of claim 7, wherein the candidate compound binds to the active site of Arabidopsis thaliana peptide deformylase.

9. The method of claim 7 further comprising synthesizing the candidate compound and screening the candidate compound for Arabidopsis thaliana peptide deformylase binding activity.