anno_start	anno_end	anno_text	entity_type	sentence	section
26	31	human	species	Structural diversity in a human antibody germline library	TITLE
32	40	antibody	protein_type	Structural diversity in a human antibody germline library	TITLE
11	19	antibody	protein_type	To support antibody therapeutic development, the crystal structures of a set of 16 germline variants composed of 4 different kappa light chains paired with 4 different heavy chains have been determined.	ABSTRACT
49	67	crystal structures	evidence	To support antibody therapeutic development, the crystal structures of a set of 16 germline variants composed of 4 different kappa light chains paired with 4 different heavy chains have been determined.	ABSTRACT
125	143	kappa light chains	structure_element	To support antibody therapeutic development, the crystal structures of a set of 16 germline variants composed of 4 different kappa light chains paired with 4 different heavy chains have been determined.	ABSTRACT
168	180	heavy chains	structure_element	To support antibody therapeutic development, the crystal structures of a set of 16 germline variants composed of 4 different kappa light chains paired with 4 different heavy chains have been determined.	ABSTRACT
9	21	heavy chains	structure_element	All four heavy chains of the antigen-binding fragments (Fabs) have the same complementarity-determining region (CDR) H3 that was reported in an earlier Fab structure.	ABSTRACT
29	54	antigen-binding fragments	structure_element	All four heavy chains of the antigen-binding fragments (Fabs) have the same complementarity-determining region (CDR) H3 that was reported in an earlier Fab structure.	ABSTRACT
56	60	Fabs	structure_element	All four heavy chains of the antigen-binding fragments (Fabs) have the same complementarity-determining region (CDR) H3 that was reported in an earlier Fab structure.	ABSTRACT
76	110	complementarity-determining region	structure_element	All four heavy chains of the antigen-binding fragments (Fabs) have the same complementarity-determining region (CDR) H3 that was reported in an earlier Fab structure.	ABSTRACT
112	115	CDR	structure_element	All four heavy chains of the antigen-binding fragments (Fabs) have the same complementarity-determining region (CDR) H3 that was reported in an earlier Fab structure.	ABSTRACT
117	119	H3	structure_element	All four heavy chains of the antigen-binding fragments (Fabs) have the same complementarity-determining region (CDR) H3 that was reported in an earlier Fab structure.	ABSTRACT
152	155	Fab	structure_element	All four heavy chains of the antigen-binding fragments (Fabs) have the same complementarity-determining region (CDR) H3 that was reported in an earlier Fab structure.	ABSTRACT
156	165	structure	evidence	All four heavy chains of the antigen-binding fragments (Fabs) have the same complementarity-determining region (CDR) H3 that was reported in an earlier Fab structure.	ABSTRACT
4	22	structure analyses	experimental_method	The structure analyses include comparisons of the overall structures, canonical structures of the CDRs and the VH:VL packing interactions.	ABSTRACT
58	68	structures	evidence	The structure analyses include comparisons of the overall structures, canonical structures of the CDRs and the VH:VL packing interactions.	ABSTRACT
80	90	structures	evidence	The structure analyses include comparisons of the overall structures, canonical structures of the CDRs and the VH:VL packing interactions.	ABSTRACT
98	102	CDRs	structure_element	The structure analyses include comparisons of the overall structures, canonical structures of the CDRs and the VH:VL packing interactions.	ABSTRACT
111	137	VH:VL packing interactions	site	The structure analyses include comparisons of the overall structures, canonical structures of the CDRs and the VH:VL packing interactions.	ABSTRACT
4	7	CDR	structure_element	The CDR conformations for the most part are tightly clustered, especially for the ones with shorter lengths.	ABSTRACT
4	10	longer	protein_state	The longer CDRs with tandem glycines or serines have more conformational diversity than the others.	ABSTRACT
11	15	CDRs	structure_element	The longer CDRs with tandem glycines or serines have more conformational diversity than the others.	ABSTRACT
28	36	glycines	residue_name	The longer CDRs with tandem glycines or serines have more conformational diversity than the others.	ABSTRACT
40	47	serines	residue_name	The longer CDRs with tandem glycines or serines have more conformational diversity than the others.	ABSTRACT
0	3	CDR	structure_element	CDR H3, despite having the same amino acid sequence, exhibits the largest conformational diversity.	ABSTRACT
4	6	H3	structure_element	CDR H3, despite having the same amino acid sequence, exhibits the largest conformational diversity.	ABSTRACT
18	28	structures	evidence	About half of the structures have CDR H3 conformations similar to that of the parent; the others diverge significantly.	ABSTRACT
34	37	CDR	structure_element	About half of the structures have CDR H3 conformations similar to that of the parent; the others diverge significantly.	ABSTRACT
38	40	H3	structure_element	About half of the structures have CDR H3 conformations similar to that of the parent; the others diverge significantly.	ABSTRACT
27	30	CDR	structure_element	One conclusion is that the CDR H3 conformations are influenced by both their amino acid sequence and their structural environment determined by the heavy and light chain pairing.	ABSTRACT
31	33	H3	structure_element	One conclusion is that the CDR H3 conformations are influenced by both their amino acid sequence and their structural environment determined by the heavy and light chain pairing.	ABSTRACT
148	153	heavy	structure_element	One conclusion is that the CDR H3 conformations are influenced by both their amino acid sequence and their structural environment determined by the heavy and light chain pairing.	ABSTRACT
158	169	light chain	structure_element	One conclusion is that the CDR H3 conformations are influenced by both their amino acid sequence and their structural environment determined by the heavy and light chain pairing.	ABSTRACT
4	16	stem regions	structure_element	The stem regions of 14 of the variant pairs are in the ‘kinked’ conformation, and only 2 are in the extended conformation.	ABSTRACT
56	62	kinked	protein_state	The stem regions of 14 of the variant pairs are in the ‘kinked’ conformation, and only 2 are in the extended conformation.	ABSTRACT
100	108	extended	protein_state	The stem regions of 14 of the variant pairs are in the ‘kinked’ conformation, and only 2 are in the extended conformation.	ABSTRACT
19	21	VH	structure_element	The packing of the VH and VL domains is consistent with our knowledge of antibody structure, and the tilt angles between these domains cover a range of 11 degrees.	ABSTRACT
26	28	VL	structure_element	The packing of the VH and VL domains is consistent with our knowledge of antibody structure, and the tilt angles between these domains cover a range of 11 degrees.	ABSTRACT
73	81	antibody	protein_type	The packing of the VH and VL domains is consistent with our knowledge of antibody structure, and the tilt angles between these domains cover a range of 11 degrees.	ABSTRACT
82	91	structure	evidence	The packing of the VH and VL domains is consistent with our knowledge of antibody structure, and the tilt angles between these domains cover a range of 11 degrees.	ABSTRACT
101	112	tilt angles	evidence	The packing of the VH and VL domains is consistent with our knowledge of antibody structure, and the tilt angles between these domains cover a range of 11 degrees.	ABSTRACT
10	20	structures	evidence	Two of 16 structures showed particularly large variations in the tilt angles when compared with the other pairings.	ABSTRACT
65	76	tilt angles	evidence	Two of 16 structures showed particularly large variations in the tilt angles when compared with the other pairings.	ABSTRACT
4	14	structures	evidence	The structures and their analyses provide a rich foundation for future antibody modeling and engineering efforts.	ABSTRACT
71	79	antibody	protein_type	The structures and their analyses provide a rich foundation for future antibody modeling and engineering efforts.	ABSTRACT
24	34	antibodies	protein_type	At present, therapeutic antibodies are the largest class of biotherapeutic proteins that are in clinical trials.	INTRO
22	32	antibodies	protein_type	The use of monoclonal antibodies as therapeutics began in the early 1980s, and their composition has transitioned from murine antibodies to generally less immunogenic humanized and human antibodies.	INTRO
119	125	murine	taxonomy_domain	The use of monoclonal antibodies as therapeutics began in the early 1980s, and their composition has transitioned from murine antibodies to generally less immunogenic humanized and human antibodies.	INTRO
126	136	antibodies	protein_type	The use of monoclonal antibodies as therapeutics began in the early 1980s, and their composition has transitioned from murine antibodies to generally less immunogenic humanized and human antibodies.	INTRO
181	186	human	species	The use of monoclonal antibodies as therapeutics began in the early 1980s, and their composition has transitioned from murine antibodies to generally less immunogenic humanized and human antibodies.	INTRO
187	197	antibodies	protein_type	The use of monoclonal antibodies as therapeutics began in the early 1980s, and their composition has transitioned from murine antibodies to generally less immunogenic humanized and human antibodies.	INTRO
42	47	human	species	The technologies currently used to obtain human antibodies include transgenic mice containing human antibody repertoires, cloning directly from human B cells, and in vitro selection from antibody libraries using various display technologies.	INTRO
48	58	antibodies	protein_type	The technologies currently used to obtain human antibodies include transgenic mice containing human antibody repertoires, cloning directly from human B cells, and in vitro selection from antibody libraries using various display technologies.	INTRO
78	82	mice	taxonomy_domain	The technologies currently used to obtain human antibodies include transgenic mice containing human antibody repertoires, cloning directly from human B cells, and in vitro selection from antibody libraries using various display technologies.	INTRO
94	99	human	species	The technologies currently used to obtain human antibodies include transgenic mice containing human antibody repertoires, cloning directly from human B cells, and in vitro selection from antibody libraries using various display technologies.	INTRO
100	108	antibody	protein_type	The technologies currently used to obtain human antibodies include transgenic mice containing human antibody repertoires, cloning directly from human B cells, and in vitro selection from antibody libraries using various display technologies.	INTRO
144	149	human	species	The technologies currently used to obtain human antibodies include transgenic mice containing human antibody repertoires, cloning directly from human B cells, and in vitro selection from antibody libraries using various display technologies.	INTRO
163	181	in vitro selection	experimental_method	The technologies currently used to obtain human antibodies include transgenic mice containing human antibody repertoires, cloning directly from human B cells, and in vitro selection from antibody libraries using various display technologies.	INTRO
187	205	antibody libraries	experimental_method	The technologies currently used to obtain human antibodies include transgenic mice containing human antibody repertoires, cloning directly from human B cells, and in vitro selection from antibody libraries using various display technologies.	INTRO
17	25	antibody	protein_type	Once a candidate antibody is identified, protein engineering is usually required to produce a molecule with the right biophysical and functional properties.	INTRO
41	60	protein engineering	experimental_method	Once a candidate antibody is identified, protein engineering is usually required to produce a molecule with the right biophysical and functional properties.	INTRO
63	80	atomic structures	evidence	All engineering efforts are guided by our understanding of the atomic structures of antibodies.	INTRO
84	94	antibodies	protein_type	All engineering efforts are guided by our understanding of the atomic structures of antibodies.	INTRO
21	38	crystal structure	evidence	In such efforts, the crystal structure of the specific antibody may not be available, but modeling can be used to guide the engineering efforts.	INTRO
55	63	antibody	protein_type	In such efforts, the crystal structure of the specific antibody may not be available, but modeling can be used to guide the engineering efforts.	INTRO
8	16	antibody	protein_type	Today's antibody modeling approaches, which normally focus on the variable region, are being developed by the application of structural principles and insights that are evolving as our knowledge of antibody structures continues to expand.	INTRO
66	81	variable region	structure_element	Today's antibody modeling approaches, which normally focus on the variable region, are being developed by the application of structural principles and insights that are evolving as our knowledge of antibody structures continues to expand.	INTRO
198	206	antibody	protein_type	Today's antibody modeling approaches, which normally focus on the variable region, are being developed by the application of structural principles and insights that are evolving as our knowledge of antibody structures continues to expand.	INTRO
207	217	structures	evidence	Today's antibody modeling approaches, which normally focus on the variable region, are being developed by the application of structural principles and insights that are evolving as our knowledge of antibody structures continues to expand.	INTRO
36	46	antibodies	protein_type	Our current structural knowledge of antibodies is based on a multitude of studies that used many techniques to gain insight into the functional and structural properties of this class of macromolecule.	INTRO
15	23	antibody	protein_type	Five different antibody isotypes occur, IgG, IgD, IgE, IgA and IgM, and each isotype has a unique role in the adaptive immune system.	INTRO
40	43	IgG	protein	Five different antibody isotypes occur, IgG, IgD, IgE, IgA and IgM, and each isotype has a unique role in the adaptive immune system.	INTRO
45	48	IgD	protein	Five different antibody isotypes occur, IgG, IgD, IgE, IgA and IgM, and each isotype has a unique role in the adaptive immune system.	INTRO
50	53	IgE	protein	Five different antibody isotypes occur, IgG, IgD, IgE, IgA and IgM, and each isotype has a unique role in the adaptive immune system.	INTRO
55	58	IgA	protein	Five different antibody isotypes occur, IgG, IgD, IgE, IgA and IgM, and each isotype has a unique role in the adaptive immune system.	INTRO
63	66	IgM	protein	Five different antibody isotypes occur, IgG, IgD, IgE, IgA and IgM, and each isotype has a unique role in the adaptive immune system.	INTRO
0	3	IgG	protein	IgG, IgD and IgE isotypes are composed of 2 heavy chains (HCs) and 2 light chains (LCs) linked through disulfide bonds, while IgA and IgM are double and quintuple versions of antibodies, respectively.	INTRO
5	8	IgD	protein	IgG, IgD and IgE isotypes are composed of 2 heavy chains (HCs) and 2 light chains (LCs) linked through disulfide bonds, while IgA and IgM are double and quintuple versions of antibodies, respectively.	INTRO
13	16	IgE	protein	IgG, IgD and IgE isotypes are composed of 2 heavy chains (HCs) and 2 light chains (LCs) linked through disulfide bonds, while IgA and IgM are double and quintuple versions of antibodies, respectively.	INTRO
44	56	heavy chains	structure_element	IgG, IgD and IgE isotypes are composed of 2 heavy chains (HCs) and 2 light chains (LCs) linked through disulfide bonds, while IgA and IgM are double and quintuple versions of antibodies, respectively.	INTRO
58	61	HCs	structure_element	IgG, IgD and IgE isotypes are composed of 2 heavy chains (HCs) and 2 light chains (LCs) linked through disulfide bonds, while IgA and IgM are double and quintuple versions of antibodies, respectively.	INTRO
69	81	light chains	structure_element	IgG, IgD and IgE isotypes are composed of 2 heavy chains (HCs) and 2 light chains (LCs) linked through disulfide bonds, while IgA and IgM are double and quintuple versions of antibodies, respectively.	INTRO
83	86	LCs	structure_element	IgG, IgD and IgE isotypes are composed of 2 heavy chains (HCs) and 2 light chains (LCs) linked through disulfide bonds, while IgA and IgM are double and quintuple versions of antibodies, respectively.	INTRO
103	118	disulfide bonds	ptm	IgG, IgD and IgE isotypes are composed of 2 heavy chains (HCs) and 2 light chains (LCs) linked through disulfide bonds, while IgA and IgM are double and quintuple versions of antibodies, respectively.	INTRO
126	129	IgA	protein	IgG, IgD and IgE isotypes are composed of 2 heavy chains (HCs) and 2 light chains (LCs) linked through disulfide bonds, while IgA and IgM are double and quintuple versions of antibodies, respectively.	INTRO
134	137	IgM	protein	IgG, IgD and IgE isotypes are composed of 2 heavy chains (HCs) and 2 light chains (LCs) linked through disulfide bonds, while IgA and IgM are double and quintuple versions of antibodies, respectively.	INTRO
175	185	antibodies	protein_type	IgG, IgD and IgE isotypes are composed of 2 heavy chains (HCs) and 2 light chains (LCs) linked through disulfide bonds, while IgA and IgM are double and quintuple versions of antibodies, respectively.	INTRO
9	12	IgG	protein	Isotypes IgG, IgD and IgA each have 4 domains, one variable (V) and 3 constant (C) domains, while IgE and IgM each have the same 4 domains along with an additional C domain.	INTRO
14	17	IgD	protein	Isotypes IgG, IgD and IgA each have 4 domains, one variable (V) and 3 constant (C) domains, while IgE and IgM each have the same 4 domains along with an additional C domain.	INTRO
22	25	IgA	protein	Isotypes IgG, IgD and IgA each have 4 domains, one variable (V) and 3 constant (C) domains, while IgE and IgM each have the same 4 domains along with an additional C domain.	INTRO
51	59	variable	structure_element	Isotypes IgG, IgD and IgA each have 4 domains, one variable (V) and 3 constant (C) domains, while IgE and IgM each have the same 4 domains along with an additional C domain.	INTRO
61	62	V	structure_element	Isotypes IgG, IgD and IgA each have 4 domains, one variable (V) and 3 constant (C) domains, while IgE and IgM each have the same 4 domains along with an additional C domain.	INTRO
70	78	constant	structure_element	Isotypes IgG, IgD and IgA each have 4 domains, one variable (V) and 3 constant (C) domains, while IgE and IgM each have the same 4 domains along with an additional C domain.	INTRO
80	81	C	structure_element	Isotypes IgG, IgD and IgA each have 4 domains, one variable (V) and 3 constant (C) domains, while IgE and IgM each have the same 4 domains along with an additional C domain.	INTRO
98	101	IgE	protein	Isotypes IgG, IgD and IgA each have 4 domains, one variable (V) and 3 constant (C) domains, while IgE and IgM each have the same 4 domains along with an additional C domain.	INTRO
106	109	IgM	protein	Isotypes IgG, IgD and IgA each have 4 domains, one variable (V) and 3 constant (C) domains, while IgE and IgM each have the same 4 domains along with an additional C domain.	INTRO
164	172	C domain	structure_element	Isotypes IgG, IgD and IgA each have 4 domains, one variable (V) and 3 constant (C) domains, while IgE and IgM each have the same 4 domains along with an additional C domain.	INTRO
53	54	J	structure_element	These multimeric forms are linked with an additional J chain.	INTRO
4	7	LCs	structure_element	The LCs that associate with the HCs are divided into 2 functionally indistinguishable classes, κ and λ.	INTRO
32	35	HCs	structure_element	The LCs that associate with the HCs are divided into 2 functionally indistinguishable classes, κ and λ.	INTRO
95	96	κ	structure_element	The LCs that associate with the HCs are divided into 2 functionally indistinguishable classes, κ and λ.	INTRO
101	102	λ	structure_element	The LCs that associate with the HCs are divided into 2 functionally indistinguishable classes, κ and λ.	INTRO
5	6	κ	structure_element	Both κ and λ polypeptide chains are composed of a single V domain and a single C domain.	INTRO
11	12	λ	structure_element	Both κ and λ polypeptide chains are composed of a single V domain and a single C domain.	INTRO
57	65	V domain	structure_element	Both κ and λ polypeptide chains are composed of a single V domain and a single C domain.	INTRO
79	87	C domain	structure_element	Both κ and λ polypeptide chains are composed of a single V domain and a single C domain.	INTRO
4	9	heavy	structure_element	The heavy and light chains are composed of structural domains that have ∼110 amino acid residues.	INTRO
14	26	light chains	structure_element	The heavy and light chains are composed of structural domains that have ∼110 amino acid residues.	INTRO
43	61	structural domains	structure_element	The heavy and light chains are composed of structural domains that have ∼110 amino acid residues.	INTRO
72	96	∼110 amino acid residues	residue_range	The heavy and light chains are composed of structural domains that have ∼110 amino acid residues.	INTRO
70	89	immunoglobulin fold	structure_element	These domains have a common folding pattern often referred to as the “immunoglobulin fold,” formed by the packing together of 2 anti-parallel β-sheets.	INTRO
128	150	anti-parallel β-sheets	structure_element	These domains have a common folding pattern often referred to as the “immunoglobulin fold,” formed by the packing together of 2 anti-parallel β-sheets.	INTRO
4	25	immunoglobulin chains	protein_type	All immunoglobulin chains have an N-terminal V domain followed by 1 to 4 C domains, depending upon the chain type.	INTRO
45	53	V domain	structure_element	All immunoglobulin chains have an N-terminal V domain followed by 1 to 4 C domains, depending upon the chain type.	INTRO
73	82	C domains	structure_element	All immunoglobulin chains have an N-terminal V domain followed by 1 to 4 C domains, depending upon the chain type.	INTRO
3	13	antibodies	protein_type	In antibodies, the heavy and light chain V domains pack together forming the antigen combining site.	INTRO
19	40	heavy and light chain	structure_element	In antibodies, the heavy and light chain V domains pack together forming the antigen combining site.	INTRO
41	50	V domains	structure_element	In antibodies, the heavy and light chain V domains pack together forming the antigen combining site.	INTRO
77	99	antigen combining site	site	In antibodies, the heavy and light chain V domains pack together forming the antigen combining site.	INTRO
81	89	antibody	protein_type	This site, which interacts with the antigen (or target), is the focus of current antibody modeling efforts.	INTRO
5	21	interaction site	site	This interaction site is composed of 6 complementarity-determining regions (CDRs) that were identified in early antibody amino acid sequence analyses to be hypervariable in nature, and thus are responsible for the sequence and structural diversity of our antibody repertoire.	INTRO
39	74	complementarity-determining regions	structure_element	This interaction site is composed of 6 complementarity-determining regions (CDRs) that were identified in early antibody amino acid sequence analyses to be hypervariable in nature, and thus are responsible for the sequence and structural diversity of our antibody repertoire.	INTRO
76	80	CDRs	structure_element	This interaction site is composed of 6 complementarity-determining regions (CDRs) that were identified in early antibody amino acid sequence analyses to be hypervariable in nature, and thus are responsible for the sequence and structural diversity of our antibody repertoire.	INTRO
112	149	antibody amino acid sequence analyses	experimental_method	This interaction site is composed of 6 complementarity-determining regions (CDRs) that were identified in early antibody amino acid sequence analyses to be hypervariable in nature, and thus are responsible for the sequence and structural diversity of our antibody repertoire.	INTRO
156	169	hypervariable	protein_state	This interaction site is composed of 6 complementarity-determining regions (CDRs) that were identified in early antibody amino acid sequence analyses to be hypervariable in nature, and thus are responsible for the sequence and structural diversity of our antibody repertoire.	INTRO
255	263	antibody	protein_type	This interaction site is composed of 6 complementarity-determining regions (CDRs) that were identified in early antibody amino acid sequence analyses to be hypervariable in nature, and thus are responsible for the sequence and structural diversity of our antibody repertoire.	INTRO
30	41	CDR regions	structure_element	The sequence diversity of the CDR regions presents a substantial challenge to antibody modeling.	INTRO
78	86	antibody	protein_type	The sequence diversity of the CDR regions presents a substantial challenge to antibody modeling.	INTRO
20	39	structural analysis	experimental_method	However, an initial structural analysis of the combining sites of the small set of structures of immunoglobulin fragments available in the 1980s found that 5 of the 6 hypervariable loops or CDRs had canonical structures (a limited set of main-chain conformations).	INTRO
47	62	combining sites	site	However, an initial structural analysis of the combining sites of the small set of structures of immunoglobulin fragments available in the 1980s found that 5 of the 6 hypervariable loops or CDRs had canonical structures (a limited set of main-chain conformations).	INTRO
83	93	structures	evidence	However, an initial structural analysis of the combining sites of the small set of structures of immunoglobulin fragments available in the 1980s found that 5 of the 6 hypervariable loops or CDRs had canonical structures (a limited set of main-chain conformations).	INTRO
167	186	hypervariable loops	structure_element	However, an initial structural analysis of the combining sites of the small set of structures of immunoglobulin fragments available in the 1980s found that 5 of the 6 hypervariable loops or CDRs had canonical structures (a limited set of main-chain conformations).	INTRO
190	194	CDRs	structure_element	However, an initial structural analysis of the combining sites of the small set of structures of immunoglobulin fragments available in the 1980s found that 5 of the 6 hypervariable loops or CDRs had canonical structures (a limited set of main-chain conformations).	INTRO
2	5	CDR	structure_element	A CDR canonical structure is defined by its length and conserved residues located in the hypervariable loop and framework residues (V-region residues that are not part of the CDRs).	INTRO
89	107	hypervariable loop	structure_element	A CDR canonical structure is defined by its length and conserved residues located in the hypervariable loop and framework residues (V-region residues that are not part of the CDRs).	INTRO
112	130	framework residues	structure_element	A CDR canonical structure is defined by its length and conserved residues located in the hypervariable loop and framework residues (V-region residues that are not part of the CDRs).	INTRO
132	140	V-region	structure_element	A CDR canonical structure is defined by its length and conserved residues located in the hypervariable loop and framework residues (V-region residues that are not part of the CDRs).	INTRO
175	179	CDRs	structure_element	A CDR canonical structure is defined by its length and conserved residues located in the hypervariable loop and framework residues (V-region residues that are not part of the CDRs).	INTRO
24	32	antibody	protein_type	Furthermore, studies of antibody sequences revealed that the total number of canonical structures are limited for each CDR, indicating possibly that antigen recognition may be affected by structural restrictions at the antigen-binding site.	INTRO
119	122	CDR	structure_element	Furthermore, studies of antibody sequences revealed that the total number of canonical structures are limited for each CDR, indicating possibly that antigen recognition may be affected by structural restrictions at the antigen-binding site.	INTRO
219	239	antigen-binding site	site	Furthermore, studies of antibody sequences revealed that the total number of canonical structures are limited for each CDR, indicating possibly that antigen recognition may be affected by structural restrictions at the antigen-binding site.	INTRO
29	37	CDR loop	structure_element	Later studies found that the CDR loop length is the primary determining factor of antigen-binding site topography because it is the primary factor for determining a canonical structure.	INTRO
82	102	antigen-binding site	site	Later studies found that the CDR loop length is the primary determining factor of antigen-binding site topography because it is the primary factor for determining a canonical structure.	INTRO
66	68	LC	structure_element	Additional efforts have led to our current understanding that the LC CDRs L1, L2, and L3 have preferred sets of canonical structures based on length and amino acid sequence composition.	INTRO
69	73	CDRs	structure_element	Additional efforts have led to our current understanding that the LC CDRs L1, L2, and L3 have preferred sets of canonical structures based on length and amino acid sequence composition.	INTRO
74	76	L1	structure_element	Additional efforts have led to our current understanding that the LC CDRs L1, L2, and L3 have preferred sets of canonical structures based on length and amino acid sequence composition.	INTRO
78	80	L2	structure_element	Additional efforts have led to our current understanding that the LC CDRs L1, L2, and L3 have preferred sets of canonical structures based on length and amino acid sequence composition.	INTRO
86	88	L3	structure_element	Additional efforts have led to our current understanding that the LC CDRs L1, L2, and L3 have preferred sets of canonical structures based on length and amino acid sequence composition.	INTRO
43	45	H1	structure_element	This was also found to be the case for the H1 and H2 CDRs.	INTRO
50	52	H2	structure_element	This was also found to be the case for the H1 and H2 CDRs.	INTRO
53	57	CDRs	structure_element	This was also found to be the case for the H1 and H2 CDRs.	INTRO
63	67	CDRs	structure_element	Classification schemes for the canonical structures of these 5 CDRs have emerged and evolved as the number of depositions in the Protein Data Bank of Fab fragments of antibodies grow.	INTRO
150	153	Fab	structure_element	Classification schemes for the canonical structures of these 5 CDRs have emerged and evolved as the number of depositions in the Protein Data Bank of Fab fragments of antibodies grow.	INTRO
167	177	antibodies	protein_type	Classification schemes for the canonical structures of these 5 CDRs have emerged and evolved as the number of depositions in the Protein Data Bank of Fab fragments of antibodies grow.	INTRO
26	29	CDR	structure_element	Recently, a comprehensive CDR classification scheme was reported identifying 72 clusters of conformations observed in antibody structures.	INTRO
118	126	antibody	protein_type	Recently, a comprehensive CDR classification scheme was reported identifying 72 clusters of conformations observed in antibody structures.	INTRO
127	137	structures	evidence	Recently, a comprehensive CDR classification scheme was reported identifying 72 clusters of conformations observed in antibody structures.	INTRO
42	45	CDR	structure_element	The knowledge and predictability of these CDR canonical structures have greatly advanced antibody modeling efforts.	INTRO
56	66	structures	evidence	The knowledge and predictability of these CDR canonical structures have greatly advanced antibody modeling efforts.	INTRO
89	97	antibody	protein_type	The knowledge and predictability of these CDR canonical structures have greatly advanced antibody modeling efforts.	INTRO
15	19	CDRs	structure_element	In contrast to CDRs L1, L2, L3, H1 and H2, no canonical structures have been observed for CDR H3, which is the most variable in length and amino acid sequence.	INTRO
20	22	L1	structure_element	In contrast to CDRs L1, L2, L3, H1 and H2, no canonical structures have been observed for CDR H3, which is the most variable in length and amino acid sequence.	INTRO
24	26	L2	structure_element	In contrast to CDRs L1, L2, L3, H1 and H2, no canonical structures have been observed for CDR H3, which is the most variable in length and amino acid sequence.	INTRO
28	30	L3	structure_element	In contrast to CDRs L1, L2, L3, H1 and H2, no canonical structures have been observed for CDR H3, which is the most variable in length and amino acid sequence.	INTRO
32	34	H1	structure_element	In contrast to CDRs L1, L2, L3, H1 and H2, no canonical structures have been observed for CDR H3, which is the most variable in length and amino acid sequence.	INTRO
39	41	H2	structure_element	In contrast to CDRs L1, L2, L3, H1 and H2, no canonical structures have been observed for CDR H3, which is the most variable in length and amino acid sequence.	INTRO
56	66	structures	evidence	In contrast to CDRs L1, L2, L3, H1 and H2, no canonical structures have been observed for CDR H3, which is the most variable in length and amino acid sequence.	INTRO
90	93	CDR	structure_element	In contrast to CDRs L1, L2, L3, H1 and H2, no canonical structures have been observed for CDR H3, which is the most variable in length and amino acid sequence.	INTRO
94	96	H3	structure_element	In contrast to CDRs L1, L2, L3, H1 and H2, no canonical structures have been observed for CDR H3, which is the most variable in length and amino acid sequence.	INTRO
96	101	loops	structure_element	Some clustering of conformations was observed for the shortest lengths; however, for the longer loops, only the portions nearest the framework (torso, stem or anchor region) were found to have defined conformations.	INTRO
133	142	framework	structure_element	Some clustering of conformations was observed for the shortest lengths; however, for the longer loops, only the portions nearest the framework (torso, stem or anchor region) were found to have defined conformations.	INTRO
144	149	torso	structure_element	Some clustering of conformations was observed for the shortest lengths; however, for the longer loops, only the portions nearest the framework (torso, stem or anchor region) were found to have defined conformations.	INTRO
151	155	stem	structure_element	Some clustering of conformations was observed for the shortest lengths; however, for the longer loops, only the portions nearest the framework (torso, stem or anchor region) were found to have defined conformations.	INTRO
159	172	anchor region	structure_element	Some clustering of conformations was observed for the shortest lengths; however, for the longer loops, only the portions nearest the framework (torso, stem or anchor region) were found to have defined conformations.	INTRO
7	19	torso region	structure_element	In the torso region, 2 primary groups could be identified, which led to sequence-based rules that can predict with some degree of reliability the conformation of the stem region.	INTRO
166	177	stem region	structure_element	In the torso region, 2 primary groups could be identified, which led to sequence-based rules that can predict with some degree of reliability the conformation of the stem region.	INTRO
5	11	kinked	protein_state	The “kinked” or “bulged” conformation is the most prevalent, but an “extended” or “non-bulged” conformation is also, but less frequently, observed.	INTRO
17	23	bulged	protein_state	The “kinked” or “bulged” conformation is the most prevalent, but an “extended” or “non-bulged” conformation is also, but less frequently, observed.	INTRO
69	77	extended	protein_state	The “kinked” or “bulged” conformation is the most prevalent, but an “extended” or “non-bulged” conformation is also, but less frequently, observed.	INTRO
83	93	non-bulged	protein_state	The “kinked” or “bulged” conformation is the most prevalent, but an “extended” or “non-bulged” conformation is also, but less frequently, observed.	INTRO
83	96	anchor region	structure_element	The cataloging and development of the rules for predicting the conformation of the anchor region of CDR H3 continue to be refined, producing new insight into the CDR H3 conformations and new tools for antibody engineering.	INTRO
100	103	CDR	structure_element	The cataloging and development of the rules for predicting the conformation of the anchor region of CDR H3 continue to be refined, producing new insight into the CDR H3 conformations and new tools for antibody engineering.	INTRO
104	106	H3	structure_element	The cataloging and development of the rules for predicting the conformation of the anchor region of CDR H3 continue to be refined, producing new insight into the CDR H3 conformations and new tools for antibody engineering.	INTRO
162	165	CDR	structure_element	The cataloging and development of the rules for predicting the conformation of the anchor region of CDR H3 continue to be refined, producing new insight into the CDR H3 conformations and new tools for antibody engineering.	INTRO
166	168	H3	structure_element	The cataloging and development of the rules for predicting the conformation of the anchor region of CDR H3 continue to be refined, producing new insight into the CDR H3 conformations and new tools for antibody engineering.	INTRO
201	209	antibody	protein_type	The cataloging and development of the rules for predicting the conformation of the anchor region of CDR H3 continue to be refined, producing new insight into the CDR H3 conformations and new tools for antibody engineering.	INTRO
8	16	antibody	protein_type	Current antibody modeling approaches take advantage of the most recent advances in homology modeling, the evolving understanding of the CDR canonical structures, the emerging rules for CDR H3 modeling and the growing body of antibody structural data available from the PDB.	INTRO
83	100	homology modeling	experimental_method	Current antibody modeling approaches take advantage of the most recent advances in homology modeling, the evolving understanding of the CDR canonical structures, the emerging rules for CDR H3 modeling and the growing body of antibody structural data available from the PDB.	INTRO
136	139	CDR	structure_element	Current antibody modeling approaches take advantage of the most recent advances in homology modeling, the evolving understanding of the CDR canonical structures, the emerging rules for CDR H3 modeling and the growing body of antibody structural data available from the PDB.	INTRO
150	160	structures	evidence	Current antibody modeling approaches take advantage of the most recent advances in homology modeling, the evolving understanding of the CDR canonical structures, the emerging rules for CDR H3 modeling and the growing body of antibody structural data available from the PDB.	INTRO
185	188	CDR	structure_element	Current antibody modeling approaches take advantage of the most recent advances in homology modeling, the evolving understanding of the CDR canonical structures, the emerging rules for CDR H3 modeling and the growing body of antibody structural data available from the PDB.	INTRO
189	191	H3	structure_element	Current antibody modeling approaches take advantage of the most recent advances in homology modeling, the evolving understanding of the CDR canonical structures, the emerging rules for CDR H3 modeling and the growing body of antibody structural data available from the PDB.	INTRO
225	233	antibody	protein_type	Current antibody modeling approaches take advantage of the most recent advances in homology modeling, the evolving understanding of the CDR canonical structures, the emerging rules for CDR H3 modeling and the growing body of antibody structural data available from the PDB.	INTRO
7	36	antibody modeling assessments	experimental_method	Recent antibody modeling assessments show continued improvement in the quality of the models being generated by a variety of modeling methods.	INTRO
9	17	antibody	protein_type	Although antibody modeling is improving, the latest assessment revealed a number of challenges that need to be overcome to provide accurate 3-dimensional models of antibody V regions, including accuracies in the modeling of CDR H3.	INTRO
164	172	antibody	protein_type	Although antibody modeling is improving, the latest assessment revealed a number of challenges that need to be overcome to provide accurate 3-dimensional models of antibody V regions, including accuracies in the modeling of CDR H3.	INTRO
173	182	V regions	structure_element	Although antibody modeling is improving, the latest assessment revealed a number of challenges that need to be overcome to provide accurate 3-dimensional models of antibody V regions, including accuracies in the modeling of CDR H3.	INTRO
224	227	CDR	structure_element	Although antibody modeling is improving, the latest assessment revealed a number of challenges that need to be overcome to provide accurate 3-dimensional models of antibody V regions, including accuracies in the modeling of CDR H3.	INTRO
228	230	H3	structure_element	Although antibody modeling is improving, the latest assessment revealed a number of challenges that need to be overcome to provide accurate 3-dimensional models of antibody V regions, including accuracies in the modeling of CDR H3.	INTRO
137	145	antibody	protein_type	The need for improvement in this area was also highlighted in a recent study reporting an approach and results that may influence future antibody modeling efforts.	INTRO
29	58	antibody modeling assessments	experimental_method	One important finding of the antibody modeling assessments was that errors in the structural templates that are used as the basis for homology models can propagate into the final models, producing inaccuracies that may negatively influence the predictive nature of the V region model.	INTRO
134	149	homology models	experimental_method	One important finding of the antibody modeling assessments was that errors in the structural templates that are used as the basis for homology models can propagate into the final models, producing inaccuracies that may negatively influence the predictive nature of the V region model.	INTRO
269	277	V region	structure_element	One important finding of the antibody modeling assessments was that errors in the structural templates that are used as the basis for homology models can propagate into the final models, producing inaccuracies that may negatively influence the predictive nature of the V region model.	INTRO
11	19	antibody	protein_type	To support antibody engineering and therapeutic development efforts, a phage library was designed and constructed based on a limited number of scaffolds built with frequently used human germ-line IGV and IGJ gene segments that encode antigen combining sites suitable for recognition of peptides and proteins.	INTRO
71	84	phage library	experimental_method	To support antibody engineering and therapeutic development efforts, a phage library was designed and constructed based on a limited number of scaffolds built with frequently used human germ-line IGV and IGJ gene segments that encode antigen combining sites suitable for recognition of peptides and proteins.	INTRO
180	185	human	species	To support antibody engineering and therapeutic development efforts, a phage library was designed and constructed based on a limited number of scaffolds built with frequently used human germ-line IGV and IGJ gene segments that encode antigen combining sites suitable for recognition of peptides and proteins.	INTRO
196	199	IGV	structure_element	To support antibody engineering and therapeutic development efforts, a phage library was designed and constructed based on a limited number of scaffolds built with frequently used human germ-line IGV and IGJ gene segments that encode antigen combining sites suitable for recognition of peptides and proteins.	INTRO
204	207	IGJ	structure_element	To support antibody engineering and therapeutic development efforts, a phage library was designed and constructed based on a limited number of scaffolds built with frequently used human germ-line IGV and IGJ gene segments that encode antigen combining sites suitable for recognition of peptides and proteins.	INTRO
234	257	antigen combining sites	site	To support antibody engineering and therapeutic development efforts, a phage library was designed and constructed based on a limited number of scaffolds built with frequently used human germ-line IGV and IGJ gene segments that encode antigen combining sites suitable for recognition of peptides and proteins.	INTRO
5	8	Fab	structure_element	This Fab library is composed of 3 HC germlines, IGHV1-69 (H1-69), IGHV3-23 (H3-23) and IGHV5-51(H5-51), and 4 LC germlines (all κ), IGKV1-39 (L1-39), IGKV3-11 (L3-11), IGKV3-20 (L3-20) and IGKV4-1 (L4-1).	INTRO
34	36	HC	structure_element	This Fab library is composed of 3 HC germlines, IGHV1-69 (H1-69), IGHV3-23 (H3-23) and IGHV5-51(H5-51), and 4 LC germlines (all κ), IGKV1-39 (L1-39), IGKV3-11 (L3-11), IGKV3-20 (L3-20) and IGKV4-1 (L4-1).	INTRO
48	56	IGHV1-69	mutant	This Fab library is composed of 3 HC germlines, IGHV1-69 (H1-69), IGHV3-23 (H3-23) and IGHV5-51(H5-51), and 4 LC germlines (all κ), IGKV1-39 (L1-39), IGKV3-11 (L3-11), IGKV3-20 (L3-20) and IGKV4-1 (L4-1).	INTRO
58	63	H1-69	mutant	This Fab library is composed of 3 HC germlines, IGHV1-69 (H1-69), IGHV3-23 (H3-23) and IGHV5-51(H5-51), and 4 LC germlines (all κ), IGKV1-39 (L1-39), IGKV3-11 (L3-11), IGKV3-20 (L3-20) and IGKV4-1 (L4-1).	INTRO
66	74	IGHV3-23	mutant	This Fab library is composed of 3 HC germlines, IGHV1-69 (H1-69), IGHV3-23 (H3-23) and IGHV5-51(H5-51), and 4 LC germlines (all κ), IGKV1-39 (L1-39), IGKV3-11 (L3-11), IGKV3-20 (L3-20) and IGKV4-1 (L4-1).	INTRO
76	81	H3-23	mutant	This Fab library is composed of 3 HC germlines, IGHV1-69 (H1-69), IGHV3-23 (H3-23) and IGHV5-51(H5-51), and 4 LC germlines (all κ), IGKV1-39 (L1-39), IGKV3-11 (L3-11), IGKV3-20 (L3-20) and IGKV4-1 (L4-1).	INTRO
87	95	IGHV5-51	mutant	This Fab library is composed of 3 HC germlines, IGHV1-69 (H1-69), IGHV3-23 (H3-23) and IGHV5-51(H5-51), and 4 LC germlines (all κ), IGKV1-39 (L1-39), IGKV3-11 (L3-11), IGKV3-20 (L3-20) and IGKV4-1 (L4-1).	INTRO
96	101	H5-51	mutant	This Fab library is composed of 3 HC germlines, IGHV1-69 (H1-69), IGHV3-23 (H3-23) and IGHV5-51(H5-51), and 4 LC germlines (all κ), IGKV1-39 (L1-39), IGKV3-11 (L3-11), IGKV3-20 (L3-20) and IGKV4-1 (L4-1).	INTRO
110	112	LC	structure_element	This Fab library is composed of 3 HC germlines, IGHV1-69 (H1-69), IGHV3-23 (H3-23) and IGHV5-51(H5-51), and 4 LC germlines (all κ), IGKV1-39 (L1-39), IGKV3-11 (L3-11), IGKV3-20 (L3-20) and IGKV4-1 (L4-1).	INTRO
128	129	κ	structure_element	This Fab library is composed of 3 HC germlines, IGHV1-69 (H1-69), IGHV3-23 (H3-23) and IGHV5-51(H5-51), and 4 LC germlines (all κ), IGKV1-39 (L1-39), IGKV3-11 (L3-11), IGKV3-20 (L3-20) and IGKV4-1 (L4-1).	INTRO
132	140	IGKV1-39	mutant	This Fab library is composed of 3 HC germlines, IGHV1-69 (H1-69), IGHV3-23 (H3-23) and IGHV5-51(H5-51), and 4 LC germlines (all κ), IGKV1-39 (L1-39), IGKV3-11 (L3-11), IGKV3-20 (L3-20) and IGKV4-1 (L4-1).	INTRO
142	147	L1-39	mutant	This Fab library is composed of 3 HC germlines, IGHV1-69 (H1-69), IGHV3-23 (H3-23) and IGHV5-51(H5-51), and 4 LC germlines (all κ), IGKV1-39 (L1-39), IGKV3-11 (L3-11), IGKV3-20 (L3-20) and IGKV4-1 (L4-1).	INTRO
150	158	IGKV3-11	mutant	This Fab library is composed of 3 HC germlines, IGHV1-69 (H1-69), IGHV3-23 (H3-23) and IGHV5-51(H5-51), and 4 LC germlines (all κ), IGKV1-39 (L1-39), IGKV3-11 (L3-11), IGKV3-20 (L3-20) and IGKV4-1 (L4-1).	INTRO
160	165	L3-11	mutant	This Fab library is composed of 3 HC germlines, IGHV1-69 (H1-69), IGHV3-23 (H3-23) and IGHV5-51(H5-51), and 4 LC germlines (all κ), IGKV1-39 (L1-39), IGKV3-11 (L3-11), IGKV3-20 (L3-20) and IGKV4-1 (L4-1).	INTRO
168	176	IGKV3-20	mutant	This Fab library is composed of 3 HC germlines, IGHV1-69 (H1-69), IGHV3-23 (H3-23) and IGHV5-51(H5-51), and 4 LC germlines (all κ), IGKV1-39 (L1-39), IGKV3-11 (L3-11), IGKV3-20 (L3-20) and IGKV4-1 (L4-1).	INTRO
178	183	L3-20	mutant	This Fab library is composed of 3 HC germlines, IGHV1-69 (H1-69), IGHV3-23 (H3-23) and IGHV5-51(H5-51), and 4 LC germlines (all κ), IGKV1-39 (L1-39), IGKV3-11 (L3-11), IGKV3-20 (L3-20) and IGKV4-1 (L4-1).	INTRO
189	196	IGKV4-1	mutant	This Fab library is composed of 3 HC germlines, IGHV1-69 (H1-69), IGHV3-23 (H3-23) and IGHV5-51(H5-51), and 4 LC germlines (all κ), IGKV1-39 (L1-39), IGKV3-11 (L3-11), IGKV3-20 (L3-20) and IGKV4-1 (L4-1).	INTRO
198	202	L4-1	mutant	This Fab library is composed of 3 HC germlines, IGHV1-69 (H1-69), IGHV3-23 (H3-23) and IGHV5-51(H5-51), and 4 LC germlines (all κ), IGKV1-39 (L1-39), IGKV3-11 (L3-11), IGKV3-20 (L3-20) and IGKV4-1 (L4-1).	INTRO
98	108	structures	evidence	Selection of these genes was based on the high frequency of their use and their cognate canonical structures that were found binding to peptides and proteins, as well as their ability to be expressed in bacteria and displayed on filamentous phage.	INTRO
190	211	expressed in bacteria	experimental_method	Selection of these genes was based on the high frequency of their use and their cognate canonical structures that were found binding to peptides and proteins, as well as their ability to be expressed in bacteria and displayed on filamentous phage.	INTRO
216	246	displayed on filamentous phage	experimental_method	Selection of these genes was based on the high frequency of their use and their cognate canonical structures that were found binding to peptides and proteins, as well as their ability to be expressed in bacteria and displayed on filamentous phage.	INTRO
70	75	human	species	The implementation of the library involves the diversification of the human germline genes to mimic that found in natural human libraries.	INTRO
122	127	human	species	The implementation of the library involves the diversification of the human germline genes to mimic that found in natural human libraries.	INTRO
4	36	crystal structure determinations	experimental_method	The crystal structure determinations and structural analyses of all germline Fabs in the library described above along with the structures of a fourth HC germline, IGHV3-53 (H3-53), paired with the 4 LCs of the library have been carried out to support antibody therapeutic development.	INTRO
41	60	structural analyses	experimental_method	The crystal structure determinations and structural analyses of all germline Fabs in the library described above along with the structures of a fourth HC germline, IGHV3-53 (H3-53), paired with the 4 LCs of the library have been carried out to support antibody therapeutic development.	INTRO
77	81	Fabs	structure_element	The crystal structure determinations and structural analyses of all germline Fabs in the library described above along with the structures of a fourth HC germline, IGHV3-53 (H3-53), paired with the 4 LCs of the library have been carried out to support antibody therapeutic development.	INTRO
128	138	structures	evidence	The crystal structure determinations and structural analyses of all germline Fabs in the library described above along with the structures of a fourth HC germline, IGHV3-53 (H3-53), paired with the 4 LCs of the library have been carried out to support antibody therapeutic development.	INTRO
151	153	HC	structure_element	The crystal structure determinations and structural analyses of all germline Fabs in the library described above along with the structures of a fourth HC germline, IGHV3-53 (H3-53), paired with the 4 LCs of the library have been carried out to support antibody therapeutic development.	INTRO
164	172	IGHV3-53	mutant	The crystal structure determinations and structural analyses of all germline Fabs in the library described above along with the structures of a fourth HC germline, IGHV3-53 (H3-53), paired with the 4 LCs of the library have been carried out to support antibody therapeutic development.	INTRO
174	179	H3-53	mutant	The crystal structure determinations and structural analyses of all germline Fabs in the library described above along with the structures of a fourth HC germline, IGHV3-53 (H3-53), paired with the 4 LCs of the library have been carried out to support antibody therapeutic development.	INTRO
200	203	LCs	structure_element	The crystal structure determinations and structural analyses of all germline Fabs in the library described above along with the structures of a fourth HC germline, IGHV3-53 (H3-53), paired with the 4 LCs of the library have been carried out to support antibody therapeutic development.	INTRO
252	260	antibody	protein_type	The crystal structure determinations and structural analyses of all germline Fabs in the library described above along with the structures of a fourth HC germline, IGHV3-53 (H3-53), paired with the 4 LCs of the library have been carried out to support antibody therapeutic development.	INTRO
7	10	HCs	structure_element	All 16 HCs of the Fabs have the same CDR H3 that was reported in an earlier Fab structure.	INTRO
18	22	Fabs	structure_element	All 16 HCs of the Fabs have the same CDR H3 that was reported in an earlier Fab structure.	INTRO
37	40	CDR	structure_element	All 16 HCs of the Fabs have the same CDR H3 that was reported in an earlier Fab structure.	INTRO
41	43	H3	structure_element	All 16 HCs of the Fabs have the same CDR H3 that was reported in an earlier Fab structure.	INTRO
76	79	Fab	structure_element	All 16 HCs of the Fabs have the same CDR H3 that was reported in an earlier Fab structure.	INTRO
80	89	structure	evidence	All 16 HCs of the Fabs have the same CDR H3 that was reported in an earlier Fab structure.	INTRO
47	49	VH	structure_element	This is the first systematic study of the same VH and VL structures in the context of different pairings.	INTRO
54	56	VL	structure_element	This is the first systematic study of the same VH and VL structures in the context of different pairings.	INTRO
57	67	structures	evidence	This is the first systematic study of the same VH and VL structures in the context of different pairings.	INTRO
58	68	structures	evidence	The structure analyses include comparisons of the overall structures, canonical structures of the L1, L2, L3, H1 and H2 CDRs, the structures of all CDR H3s, and the VH:VL packing interactions.	INTRO
80	90	structures	evidence	The structure analyses include comparisons of the overall structures, canonical structures of the L1, L2, L3, H1 and H2 CDRs, the structures of all CDR H3s, and the VH:VL packing interactions.	INTRO
98	100	L1	structure_element	The structure analyses include comparisons of the overall structures, canonical structures of the L1, L2, L3, H1 and H2 CDRs, the structures of all CDR H3s, and the VH:VL packing interactions.	INTRO
102	104	L2	structure_element	The structure analyses include comparisons of the overall structures, canonical structures of the L1, L2, L3, H1 and H2 CDRs, the structures of all CDR H3s, and the VH:VL packing interactions.	INTRO
106	108	L3	structure_element	The structure analyses include comparisons of the overall structures, canonical structures of the L1, L2, L3, H1 and H2 CDRs, the structures of all CDR H3s, and the VH:VL packing interactions.	INTRO
110	112	H1	structure_element	The structure analyses include comparisons of the overall structures, canonical structures of the L1, L2, L3, H1 and H2 CDRs, the structures of all CDR H3s, and the VH:VL packing interactions.	INTRO
117	119	H2	structure_element	The structure analyses include comparisons of the overall structures, canonical structures of the L1, L2, L3, H1 and H2 CDRs, the structures of all CDR H3s, and the VH:VL packing interactions.	INTRO
120	124	CDRs	structure_element	The structure analyses include comparisons of the overall structures, canonical structures of the L1, L2, L3, H1 and H2 CDRs, the structures of all CDR H3s, and the VH:VL packing interactions.	INTRO
130	140	structures	evidence	The structure analyses include comparisons of the overall structures, canonical structures of the L1, L2, L3, H1 and H2 CDRs, the structures of all CDR H3s, and the VH:VL packing interactions.	INTRO
148	151	CDR	structure_element	The structure analyses include comparisons of the overall structures, canonical structures of the L1, L2, L3, H1 and H2 CDRs, the structures of all CDR H3s, and the VH:VL packing interactions.	INTRO
152	155	H3s	structure_element	The structure analyses include comparisons of the overall structures, canonical structures of the L1, L2, L3, H1 and H2 CDRs, the structures of all CDR H3s, and the VH:VL packing interactions.	INTRO
165	191	VH:VL packing interactions	site	The structure analyses include comparisons of the overall structures, canonical structures of the L1, L2, L3, H1 and H2 CDRs, the structures of all CDR H3s, and the VH:VL packing interactions.	INTRO
4	14	structures	evidence	The structures and their analyses provide a foundation for future antibody engineering and structure determination efforts.	INTRO
66	74	antibody	protein_type	The structures and their analyses provide a foundation for future antibody engineering and structure determination efforts.	INTRO
0	18	Crystal structures	evidence	Crystal structures	RESULTS
0	12	Crystal data	evidence	Crystal data, X-ray data, and refinement statistics.	TABLE
14	24	X-ray data	evidence	Crystal data, X-ray data, and refinement statistics.	TABLE
30	51	refinement statistics	evidence	Crystal data, X-ray data, and refinement statistics.	TABLE
12	24	Crystal data	evidence	(Continued) Crystal data, X-ray data, and refinement statistics.	TABLE
26	36	X-ray data	evidence	(Continued) Crystal data, X-ray data, and refinement statistics.	TABLE
42	63	refinement statistics	evidence	(Continued) Crystal data, X-ray data, and refinement statistics.	TABLE
12	24	Crystal data	evidence	(Continued) Crystal data, X-ray data, and refinement statistics.	TABLE
26	36	X-ray data	evidence	(Continued) Crystal data, X-ray data, and refinement statistics.	TABLE
42	63	refinement statistics	evidence	(Continued) Crystal data, X-ray data, and refinement statistics.	TABLE
12	24	Crystal data	evidence	(Continued) Crystal data, X-ray data, and refinement statistics.	TABLE
26	36	X-ray data	evidence	(Continued) Crystal data, X-ray data, and refinement statistics.	TABLE
42	63	refinement statistics	evidence	(Continued) Crystal data, X-ray data, and refinement statistics.	TABLE
4	22	crystal structures	evidence	The crystal structures of a germline library composed of 16 Fabs generated by combining 4 HCs (H1-69, H3-23, H3-53 and H5-51) and 4 LCs (L1-39, L3-11, L3-20 and L4-1) have been determined.	RESULTS
28	44	germline library	experimental_method	The crystal structures of a germline library composed of 16 Fabs generated by combining 4 HCs (H1-69, H3-23, H3-53 and H5-51) and 4 LCs (L1-39, L3-11, L3-20 and L4-1) have been determined.	RESULTS
60	64	Fabs	structure_element	The crystal structures of a germline library composed of 16 Fabs generated by combining 4 HCs (H1-69, H3-23, H3-53 and H5-51) and 4 LCs (L1-39, L3-11, L3-20 and L4-1) have been determined.	RESULTS
90	93	HCs	structure_element	The crystal structures of a germline library composed of 16 Fabs generated by combining 4 HCs (H1-69, H3-23, H3-53 and H5-51) and 4 LCs (L1-39, L3-11, L3-20 and L4-1) have been determined.	RESULTS
95	100	H1-69	mutant	The crystal structures of a germline library composed of 16 Fabs generated by combining 4 HCs (H1-69, H3-23, H3-53 and H5-51) and 4 LCs (L1-39, L3-11, L3-20 and L4-1) have been determined.	RESULTS
102	107	H3-23	mutant	The crystal structures of a germline library composed of 16 Fabs generated by combining 4 HCs (H1-69, H3-23, H3-53 and H5-51) and 4 LCs (L1-39, L3-11, L3-20 and L4-1) have been determined.	RESULTS
109	114	H3-53	mutant	The crystal structures of a germline library composed of 16 Fabs generated by combining 4 HCs (H1-69, H3-23, H3-53 and H5-51) and 4 LCs (L1-39, L3-11, L3-20 and L4-1) have been determined.	RESULTS
119	124	H5-51	mutant	The crystal structures of a germline library composed of 16 Fabs generated by combining 4 HCs (H1-69, H3-23, H3-53 and H5-51) and 4 LCs (L1-39, L3-11, L3-20 and L4-1) have been determined.	RESULTS
132	135	LCs	structure_element	The crystal structures of a germline library composed of 16 Fabs generated by combining 4 HCs (H1-69, H3-23, H3-53 and H5-51) and 4 LCs (L1-39, L3-11, L3-20 and L4-1) have been determined.	RESULTS
137	142	L1-39	mutant	The crystal structures of a germline library composed of 16 Fabs generated by combining 4 HCs (H1-69, H3-23, H3-53 and H5-51) and 4 LCs (L1-39, L3-11, L3-20 and L4-1) have been determined.	RESULTS
144	149	L3-11	mutant	The crystal structures of a germline library composed of 16 Fabs generated by combining 4 HCs (H1-69, H3-23, H3-53 and H5-51) and 4 LCs (L1-39, L3-11, L3-20 and L4-1) have been determined.	RESULTS
151	156	L3-20	mutant	The crystal structures of a germline library composed of 16 Fabs generated by combining 4 HCs (H1-69, H3-23, H3-53 and H5-51) and 4 LCs (L1-39, L3-11, L3-20 and L4-1) have been determined.	RESULTS
161	165	L4-1	mutant	The crystal structures of a germline library composed of 16 Fabs generated by combining 4 HCs (H1-69, H3-23, H3-53 and H5-51) and 4 LCs (L1-39, L3-11, L3-20 and L4-1) have been determined.	RESULTS
4	7	Fab	structure_element	The Fab heavy and light chain sequences for the variants numbered according to Chothia are shown in Fig. S1.	RESULTS
18	29	light chain	structure_element	The Fab heavy and light chain sequences for the variants numbered according to Chothia are shown in Fig. S1.	RESULTS
19	22	HCs	structure_element	The four different HCs all have the same CDR H3 sequence, ARYDGIYGELDF.	RESULTS
41	44	CDR	structure_element	The four different HCs all have the same CDR H3 sequence, ARYDGIYGELDF.	RESULTS
45	47	H3	structure_element	The four different HCs all have the same CDR H3 sequence, ARYDGIYGELDF.	RESULTS
58	70	ARYDGIYGELDF	structure_element	The four different HCs all have the same CDR H3 sequence, ARYDGIYGELDF.	RESULTS
0	15	Crystallization	experimental_method	Crystallization of the 16 Fabs was previously reported.	RESULTS
26	30	Fabs	structure_element	Crystallization of the 16 Fabs was previously reported.	RESULTS
18	26	crystals	evidence	Three sets of the crystals were isomorphous with nearly identical unit cells (Table 1).	RESULTS
18	29	H3-23:L3-11	complex_assembly	These include (1) H3-23:L3-11 and H3-23:L4-1 in P212121, (2) H3-53:L1-39, H3-53:L3-11 and H3-53:L3-20 in P6522, and (3) H5-51:L1-39, H5-51:L3-11 and H5-51:L3-20 in P212121.	RESULTS
34	44	H3-23:L4-1	complex_assembly	These include (1) H3-23:L3-11 and H3-23:L4-1 in P212121, (2) H3-53:L1-39, H3-53:L3-11 and H3-53:L3-20 in P6522, and (3) H5-51:L1-39, H5-51:L3-11 and H5-51:L3-20 in P212121.	RESULTS
61	72	H3-53:L1-39	complex_assembly	These include (1) H3-23:L3-11 and H3-23:L4-1 in P212121, (2) H3-53:L1-39, H3-53:L3-11 and H3-53:L3-20 in P6522, and (3) H5-51:L1-39, H5-51:L3-11 and H5-51:L3-20 in P212121.	RESULTS
74	85	H3-53:L3-11	complex_assembly	These include (1) H3-23:L3-11 and H3-23:L4-1 in P212121, (2) H3-53:L1-39, H3-53:L3-11 and H3-53:L3-20 in P6522, and (3) H5-51:L1-39, H5-51:L3-11 and H5-51:L3-20 in P212121.	RESULTS
90	101	H3-53:L3-20	complex_assembly	These include (1) H3-23:L3-11 and H3-23:L4-1 in P212121, (2) H3-53:L1-39, H3-53:L3-11 and H3-53:L3-20 in P6522, and (3) H5-51:L1-39, H5-51:L3-11 and H5-51:L3-20 in P212121.	RESULTS
120	131	H5-51:L1-39	complex_assembly	These include (1) H3-23:L3-11 and H3-23:L4-1 in P212121, (2) H3-53:L1-39, H3-53:L3-11 and H3-53:L3-20 in P6522, and (3) H5-51:L1-39, H5-51:L3-11 and H5-51:L3-20 in P212121.	RESULTS
133	144	H5-51:L3-11	complex_assembly	These include (1) H3-23:L3-11 and H3-23:L4-1 in P212121, (2) H3-53:L1-39, H3-53:L3-11 and H3-53:L3-20 in P6522, and (3) H5-51:L1-39, H5-51:L3-11 and H5-51:L3-20 in P212121.	RESULTS
149	160	H5-51:L3-20	complex_assembly	These include (1) H3-23:L3-11 and H3-23:L4-1 in P212121, (2) H3-53:L1-39, H3-53:L3-11 and H3-53:L3-20 in P6522, and (3) H5-51:L1-39, H5-51:L3-11 and H5-51:L3-20 in P212121.	RESULTS
72	80	PEG 3350	chemical	Variations occur in the pH (buffer) and the additives, and, in group 3, PEG 3350 is the precipitant for one variants while ammonium sulfate is the precipitant for the other two.	RESULTS
123	139	ammonium sulfate	chemical	Variations occur in the pH (buffer) and the additives, and, in group 3, PEG 3350 is the precipitant for one variants while ammonium sulfate is the precipitant for the other two.	RESULTS
22	35	crystal forms	evidence	The similarity in the crystal forms is attributed in part to cross-seeding using the microseed matrix screening for groups 2 and 3.	RESULTS
85	111	microseed matrix screening	experimental_method	The similarity in the crystal forms is attributed in part to cross-seeding using the microseed matrix screening for groups 2 and 3.	RESULTS
4	22	crystal structures	evidence	The crystal structures of the 16 Fabs have been determined at resolutions ranging from 3.3 Å to 1.65 Å (Table 1).	RESULTS
33	37	Fabs	structure_element	The crystal structures of the 16 Fabs have been determined at resolutions ranging from 3.3 Å to 1.65 Å (Table 1).	RESULTS
14	17	Fab	structure_element	The number of Fab molecules in the crystallographic asymmetric unit varies from 1 (for 12 Fabs) to 2 (for 4 Fabs).	RESULTS
90	94	Fabs	structure_element	The number of Fab molecules in the crystallographic asymmetric unit varies from 1 (for 12 Fabs) to 2 (for 4 Fabs).	RESULTS
108	112	Fabs	structure_element	The number of Fab molecules in the crystallographic asymmetric unit varies from 1 (for 12 Fabs) to 2 (for 4 Fabs).	RESULTS
12	22	structures	evidence	Overall the structures are fairly complete, and, as can be expected, the models for the higher resolution structures are more complete than those for the lower resolution structures (Table S1).	RESULTS
106	116	structures	evidence	Overall the structures are fairly complete, and, as can be expected, the models for the higher resolution structures are more complete than those for the lower resolution structures (Table S1).	RESULTS
171	181	structures	evidence	Overall the structures are fairly complete, and, as can be expected, the models for the higher resolution structures are more complete than those for the lower resolution structures (Table S1).	RESULTS
16	19	HCs	structure_element	Invariably, the HCs have more disorder than the LCs.	RESULTS
30	38	disorder	protein_state	Invariably, the HCs have more disorder than the LCs.	RESULTS
48	51	LCs	structure_element	Invariably, the HCs have more disorder than the LCs.	RESULTS
8	10	LC	structure_element	For the LC, the disorder is observed at 2 of the C-terminal residues with few exceptions.	RESULTS
16	24	disorder	protein_state	For the LC, the disorder is observed at 2 of the C-terminal residues with few exceptions.	RESULTS
58	60	LC	structure_element	Apart from the C-terminus, only a few surface residues in LC are disordered.	RESULTS
65	75	disordered	protein_state	Apart from the C-terminus, only a few surface residues in LC are disordered.	RESULTS
4	7	HCs	structure_element	The HCs feature the largest number of disordered residues, with the lower resolution structures having the most.	RESULTS
38	48	disordered	protein_state	The HCs feature the largest number of disordered residues, with the lower resolution structures having the most.	RESULTS
85	95	structures	evidence	The HCs feature the largest number of disordered residues, with the lower resolution structures having the most.	RESULTS
53	63	disordered	protein_state	The C-terminal residues including the 6xHis tags are disordered in all 16 structures.	RESULTS
74	84	structures	evidence	The C-terminal residues including the 6xHis tags are disordered in all 16 structures.	RESULTS
93	103	structures	evidence	In addition to these, 2 primary disordered stretches of residues are observed in a number of structures (Table S1).	RESULTS
17	21	loop	structure_element	One involves the loop connecting the first 2 β-strands of the constant domain (in all Fabs except H3-23:L1-39, H3-23:L3-11 and H3-53:L1-39).	RESULTS
45	54	β-strands	structure_element	One involves the loop connecting the first 2 β-strands of the constant domain (in all Fabs except H3-23:L1-39, H3-23:L3-11 and H3-53:L1-39).	RESULTS
62	77	constant domain	structure_element	One involves the loop connecting the first 2 β-strands of the constant domain (in all Fabs except H3-23:L1-39, H3-23:L3-11 and H3-53:L1-39).	RESULTS
86	90	Fabs	structure_element	One involves the loop connecting the first 2 β-strands of the constant domain (in all Fabs except H3-23:L1-39, H3-23:L3-11 and H3-53:L1-39).	RESULTS
98	109	H3-23:L1-39	complex_assembly	One involves the loop connecting the first 2 β-strands of the constant domain (in all Fabs except H3-23:L1-39, H3-23:L3-11 and H3-53:L1-39).	RESULTS
111	122	H3-23:L3-11	complex_assembly	One involves the loop connecting the first 2 β-strands of the constant domain (in all Fabs except H3-23:L1-39, H3-23:L3-11 and H3-53:L1-39).	RESULTS
127	138	H3-53:L1-39	complex_assembly	One involves the loop connecting the first 2 β-strands of the constant domain (in all Fabs except H3-23:L1-39, H3-23:L3-11 and H3-53:L1-39).	RESULTS
24	27	CDR	structure_element	The other is located in CDR H3 (in H5-51:L3-11, H5-51:L3-20 and in one of 2 copies of H3-23:L4-1).	RESULTS
28	30	H3	structure_element	The other is located in CDR H3 (in H5-51:L3-11, H5-51:L3-20 and in one of 2 copies of H3-23:L4-1).	RESULTS
35	46	H5-51:L3-11	complex_assembly	The other is located in CDR H3 (in H5-51:L3-11, H5-51:L3-20 and in one of 2 copies of H3-23:L4-1).	RESULTS
48	59	H5-51:L3-20	complex_assembly	The other is located in CDR H3 (in H5-51:L3-11, H5-51:L3-20 and in one of 2 copies of H3-23:L4-1).	RESULTS
86	96	H3-23:L4-1	complex_assembly	The other is located in CDR H3 (in H5-51:L3-11, H5-51:L3-20 and in one of 2 copies of H3-23:L4-1).	RESULTS
0	3	CDR	structure_element	CDR H1 and CDR H2 also show some degree of disorder, but to a lesser extent.	RESULTS
4	6	H1	structure_element	CDR H1 and CDR H2 also show some degree of disorder, but to a lesser extent.	RESULTS
11	14	CDR	structure_element	CDR H1 and CDR H2 also show some degree of disorder, but to a lesser extent.	RESULTS
15	17	H2	structure_element	CDR H1 and CDR H2 also show some degree of disorder, but to a lesser extent.	RESULTS
43	51	disorder	protein_state	CDR H1 and CDR H2 also show some degree of disorder, but to a lesser extent.	RESULTS
0	3	CDR	structure_element	CDR canonical structures	RESULTS
14	24	structures	evidence	CDR canonical structures	RESULTS
8	11	CDR	structure_element	Several CDR definitions have evolved over decades of antibody research.	RESULTS
53	61	antibody	protein_type	Several CDR definitions have evolved over decades of antibody research.	RESULTS
41	44	CDR	structure_element	Depending on the focus of the study, the CDR boundaries differ slightly between various definitions.	RESULTS
25	28	CDR	structure_element	In this work, we use the CDR definition of North et al., which is similar to that of Martin with the following exceptions: 1) CDRs H1 and H3 begin immediately after the Cys; and 2) CDR L2 includes an additional residue at the N-terminal side, typically Tyr.	RESULTS
126	130	CDRs	structure_element	In this work, we use the CDR definition of North et al., which is similar to that of Martin with the following exceptions: 1) CDRs H1 and H3 begin immediately after the Cys; and 2) CDR L2 includes an additional residue at the N-terminal side, typically Tyr.	RESULTS
131	133	H1	structure_element	In this work, we use the CDR definition of North et al., which is similar to that of Martin with the following exceptions: 1) CDRs H1 and H3 begin immediately after the Cys; and 2) CDR L2 includes an additional residue at the N-terminal side, typically Tyr.	RESULTS
138	140	H3	structure_element	In this work, we use the CDR definition of North et al., which is similar to that of Martin with the following exceptions: 1) CDRs H1 and H3 begin immediately after the Cys; and 2) CDR L2 includes an additional residue at the N-terminal side, typically Tyr.	RESULTS
169	172	Cys	residue_name	In this work, we use the CDR definition of North et al., which is similar to that of Martin with the following exceptions: 1) CDRs H1 and H3 begin immediately after the Cys; and 2) CDR L2 includes an additional residue at the N-terminal side, typically Tyr.	RESULTS
181	184	CDR	structure_element	In this work, we use the CDR definition of North et al., which is similar to that of Martin with the following exceptions: 1) CDRs H1 and H3 begin immediately after the Cys; and 2) CDR L2 includes an additional residue at the N-terminal side, typically Tyr.	RESULTS
185	187	L2	structure_element	In this work, we use the CDR definition of North et al., which is similar to that of Martin with the following exceptions: 1) CDRs H1 and H3 begin immediately after the Cys; and 2) CDR L2 includes an additional residue at the N-terminal side, typically Tyr.	RESULTS
253	256	Tyr	residue_name	In this work, we use the CDR definition of North et al., which is similar to that of Martin with the following exceptions: 1) CDRs H1 and H3 begin immediately after the Cys; and 2) CDR L2 includes an additional residue at the N-terminal side, typically Tyr.	RESULTS
0	3	CDR	structure_element	CDR H1	RESULTS
4	6	H1	structure_element	CDR H1	RESULTS
4	17	superposition	experimental_method	The superposition of CDR H1 backbones for all HC:LC pairs with heavy chains: (A) H1-69, (B) H3-23, (C) H3-53 and (D) H5-51.	FIG
21	24	CDR	structure_element	The superposition of CDR H1 backbones for all HC:LC pairs with heavy chains: (A) H1-69, (B) H3-23, (C) H3-53 and (D) H5-51.	FIG
25	27	H1	structure_element	The superposition of CDR H1 backbones for all HC:LC pairs with heavy chains: (A) H1-69, (B) H3-23, (C) H3-53 and (D) H5-51.	FIG
46	51	HC:LC	complex_assembly	The superposition of CDR H1 backbones for all HC:LC pairs with heavy chains: (A) H1-69, (B) H3-23, (C) H3-53 and (D) H5-51.	FIG
63	75	heavy chains	structure_element	The superposition of CDR H1 backbones for all HC:LC pairs with heavy chains: (A) H1-69, (B) H3-23, (C) H3-53 and (D) H5-51.	FIG
81	86	H1-69	mutant	The superposition of CDR H1 backbones for all HC:LC pairs with heavy chains: (A) H1-69, (B) H3-23, (C) H3-53 and (D) H5-51.	FIG
92	97	H3-23	mutant	The superposition of CDR H1 backbones for all HC:LC pairs with heavy chains: (A) H1-69, (B) H3-23, (C) H3-53 and (D) H5-51.	FIG
103	108	H3-53	mutant	The superposition of CDR H1 backbones for all HC:LC pairs with heavy chains: (A) H1-69, (B) H3-23, (C) H3-53 and (D) H5-51.	FIG
117	122	H5-51	mutant	The superposition of CDR H1 backbones for all HC:LC pairs with heavy chains: (A) H1-69, (B) H3-23, (C) H3-53 and (D) H5-51.	FIG
0	4	CDRs	structure_element	CDRs are defined using the Dunbrack convention [12].	TABLE
32	35	Fab	structure_element	Assignments for 2 copies of the Fab in the asymmetric unit are given for 5 structures.	TABLE
75	85	structures	evidence	Assignments for 2 copies of the Fab in the asymmetric unit are given for 5 structures.	TABLE
23	27	CDRs	structure_element	No assignment (NA) for CDRs with missing residues.	TABLE
9	12	HCs	structure_element	The four HCs feature CDR H1 of the same length, and their sequences are highly similar (Table 2).	RESULTS
21	24	CDR	structure_element	The four HCs feature CDR H1 of the same length, and their sequences are highly similar (Table 2).	RESULTS
25	27	H1	structure_element	The four HCs feature CDR H1 of the same length, and their sequences are highly similar (Table 2).	RESULTS
4	7	CDR	structure_element	The CDR H1 backbone conformations for all variants for each of the HCs are shown in Fig. 1.	RESULTS
8	10	H1	structure_element	The CDR H1 backbone conformations for all variants for each of the HCs are shown in Fig. 1.	RESULTS
67	70	HCs	structure_element	The CDR H1 backbone conformations for all variants for each of the HCs are shown in Fig. 1.	RESULTS
13	16	HCs	structure_element	Three of the HCs, H3-23, H3-53 and H5-51, have the same canonical structure, H1-13-1, and the backbone conformations are tightly clustered for each set of Fab structures as reflected in the rmsd values (Fig. 1B-D).	RESULTS
18	23	H3-23	mutant	Three of the HCs, H3-23, H3-53 and H5-51, have the same canonical structure, H1-13-1, and the backbone conformations are tightly clustered for each set of Fab structures as reflected in the rmsd values (Fig. 1B-D).	RESULTS
25	30	H3-53	mutant	Three of the HCs, H3-23, H3-53 and H5-51, have the same canonical structure, H1-13-1, and the backbone conformations are tightly clustered for each set of Fab structures as reflected in the rmsd values (Fig. 1B-D).	RESULTS
35	40	H5-51	mutant	Three of the HCs, H3-23, H3-53 and H5-51, have the same canonical structure, H1-13-1, and the backbone conformations are tightly clustered for each set of Fab structures as reflected in the rmsd values (Fig. 1B-D).	RESULTS
77	84	H1-13-1	mutant	Three of the HCs, H3-23, H3-53 and H5-51, have the same canonical structure, H1-13-1, and the backbone conformations are tightly clustered for each set of Fab structures as reflected in the rmsd values (Fig. 1B-D).	RESULTS
155	158	Fab	structure_element	Three of the HCs, H3-23, H3-53 and H5-51, have the same canonical structure, H1-13-1, and the backbone conformations are tightly clustered for each set of Fab structures as reflected in the rmsd values (Fig. 1B-D).	RESULTS
159	169	structures	evidence	Three of the HCs, H3-23, H3-53 and H5-51, have the same canonical structure, H1-13-1, and the backbone conformations are tightly clustered for each set of Fab structures as reflected in the rmsd values (Fig. 1B-D).	RESULTS
190	201	rmsd values	evidence	Three of the HCs, H3-23, H3-53 and H5-51, have the same canonical structure, H1-13-1, and the backbone conformations are tightly clustered for each set of Fab structures as reflected in the rmsd values (Fig. 1B-D).	RESULTS
31	36	H3-53	mutant	Some deviation is observed for H3-53, mostly due to H3-53:L4-1, which exhibits a significant degree of disorder in CDR H1.	RESULTS
52	62	H3-53:L4-1	complex_assembly	Some deviation is observed for H3-53, mostly due to H3-53:L4-1, which exhibits a significant degree of disorder in CDR H1.	RESULTS
115	118	CDR	structure_element	Some deviation is observed for H3-53, mostly due to H3-53:L4-1, which exhibits a significant degree of disorder in CDR H1.	RESULTS
119	121	H1	structure_element	Some deviation is observed for H3-53, mostly due to H3-53:L4-1, which exhibits a significant degree of disorder in CDR H1.	RESULTS
4	20	electron density	evidence	The electron density for the backbone is weak and discontinuous, and completely missing for several side chains.	RESULTS
4	7	CDR	structure_element	The CDR H1 structures with H1-69 shown in Fig. 1A are quite variable, both for the structures with different LCs and for the copies of the same Fab in the asymmetric unit, H1-69:L3-11 and H1-69:L3-20.	RESULTS
8	10	H1	structure_element	The CDR H1 structures with H1-69 shown in Fig. 1A are quite variable, both for the structures with different LCs and for the copies of the same Fab in the asymmetric unit, H1-69:L3-11 and H1-69:L3-20.	RESULTS
11	21	structures	evidence	The CDR H1 structures with H1-69 shown in Fig. 1A are quite variable, both for the structures with different LCs and for the copies of the same Fab in the asymmetric unit, H1-69:L3-11 and H1-69:L3-20.	RESULTS
27	32	H1-69	mutant	The CDR H1 structures with H1-69 shown in Fig. 1A are quite variable, both for the structures with different LCs and for the copies of the same Fab in the asymmetric unit, H1-69:L3-11 and H1-69:L3-20.	RESULTS
83	93	structures	evidence	The CDR H1 structures with H1-69 shown in Fig. 1A are quite variable, both for the structures with different LCs and for the copies of the same Fab in the asymmetric unit, H1-69:L3-11 and H1-69:L3-20.	RESULTS
109	112	LCs	structure_element	The CDR H1 structures with H1-69 shown in Fig. 1A are quite variable, both for the structures with different LCs and for the copies of the same Fab in the asymmetric unit, H1-69:L3-11 and H1-69:L3-20.	RESULTS
144	147	Fab	structure_element	The CDR H1 structures with H1-69 shown in Fig. 1A are quite variable, both for the structures with different LCs and for the copies of the same Fab in the asymmetric unit, H1-69:L3-11 and H1-69:L3-20.	RESULTS
172	183	H1-69:L3-11	complex_assembly	The CDR H1 structures with H1-69 shown in Fig. 1A are quite variable, both for the structures with different LCs and for the copies of the same Fab in the asymmetric unit, H1-69:L3-11 and H1-69:L3-20.	RESULTS
188	199	H1-69:L3-20	complex_assembly	The CDR H1 structures with H1-69 shown in Fig. 1A are quite variable, both for the structures with different LCs and for the copies of the same Fab in the asymmetric unit, H1-69:L3-11 and H1-69:L3-20.	RESULTS
24	27	Fab	structure_element	In total, 6 independent Fab structures produce 5 different canonical structures, namely H1-13-1, H1-13-3, H1-13-4, H1-13-6 and H1-13-10.	RESULTS
28	38	structures	evidence	In total, 6 independent Fab structures produce 5 different canonical structures, namely H1-13-1, H1-13-3, H1-13-4, H1-13-6 and H1-13-10.	RESULTS
69	79	structures	evidence	In total, 6 independent Fab structures produce 5 different canonical structures, namely H1-13-1, H1-13-3, H1-13-4, H1-13-6 and H1-13-10.	RESULTS
88	95	H1-13-1	mutant	In total, 6 independent Fab structures produce 5 different canonical structures, namely H1-13-1, H1-13-3, H1-13-4, H1-13-6 and H1-13-10.	RESULTS
97	104	H1-13-3	mutant	In total, 6 independent Fab structures produce 5 different canonical structures, namely H1-13-1, H1-13-3, H1-13-4, H1-13-6 and H1-13-10.	RESULTS
106	113	H1-13-4	mutant	In total, 6 independent Fab structures produce 5 different canonical structures, namely H1-13-1, H1-13-3, H1-13-4, H1-13-6 and H1-13-10.	RESULTS
115	122	H1-13-6	mutant	In total, 6 independent Fab structures produce 5 different canonical structures, namely H1-13-1, H1-13-3, H1-13-4, H1-13-6 and H1-13-10.	RESULTS
127	135	H1-13-10	mutant	In total, 6 independent Fab structures produce 5 different canonical structures, namely H1-13-1, H1-13-3, H1-13-4, H1-13-6 and H1-13-10.	RESULTS
22	27	H1-69	mutant	A major difference of H1-69 from the other germlines in the experimental data set is the presence of Gly instead of Phe or Tyr at position 27 (residue 5 of 13 in CDR H1).	RESULTS
101	104	Gly	residue_name	A major difference of H1-69 from the other germlines in the experimental data set is the presence of Gly instead of Phe or Tyr at position 27 (residue 5 of 13 in CDR H1).	RESULTS
116	119	Phe	residue_name	A major difference of H1-69 from the other germlines in the experimental data set is the presence of Gly instead of Phe or Tyr at position 27 (residue 5 of 13 in CDR H1).	RESULTS
123	126	Tyr	residue_name	A major difference of H1-69 from the other germlines in the experimental data set is the presence of Gly instead of Phe or Tyr at position 27 (residue 5 of 13 in CDR H1).	RESULTS
139	141	27	residue_number	A major difference of H1-69 from the other germlines in the experimental data set is the presence of Gly instead of Phe or Tyr at position 27 (residue 5 of 13 in CDR H1).	RESULTS
162	165	CDR	structure_element	A major difference of H1-69 from the other germlines in the experimental data set is the presence of Gly instead of Phe or Tyr at position 27 (residue 5 of 13 in CDR H1).	RESULTS
166	168	H1	structure_element	A major difference of H1-69 from the other germlines in the experimental data set is the presence of Gly instead of Phe or Tyr at position 27 (residue 5 of 13 in CDR H1).	RESULTS
0	7	Glycine	residue_name	Glycine introduces the possibility of a higher degree of conformational flexibility that undoubtedly translates to the differences observed, and contributes to the elevated thermal parameters for the atoms in the amino acid residues in this region.	RESULTS
0	3	CDR	structure_element	CDR H2	RESULTS
4	6	H2	structure_element	CDR H2	RESULTS
4	17	superposition	experimental_method	The superposition of CDR H2 backbones for all HC:LC pairs with heavy chains: (A) H1-69, (B) H3-23, (C) H3-53 and (D) H5-51.	FIG
21	24	CDR	structure_element	The superposition of CDR H2 backbones for all HC:LC pairs with heavy chains: (A) H1-69, (B) H3-23, (C) H3-53 and (D) H5-51.	FIG
25	27	H2	structure_element	The superposition of CDR H2 backbones for all HC:LC pairs with heavy chains: (A) H1-69, (B) H3-23, (C) H3-53 and (D) H5-51.	FIG
46	51	HC:LC	complex_assembly	The superposition of CDR H2 backbones for all HC:LC pairs with heavy chains: (A) H1-69, (B) H3-23, (C) H3-53 and (D) H5-51.	FIG
63	75	heavy chains	structure_element	The superposition of CDR H2 backbones for all HC:LC pairs with heavy chains: (A) H1-69, (B) H3-23, (C) H3-53 and (D) H5-51.	FIG
81	86	H1-69	mutant	The superposition of CDR H2 backbones for all HC:LC pairs with heavy chains: (A) H1-69, (B) H3-23, (C) H3-53 and (D) H5-51.	FIG
92	97	H3-23	mutant	The superposition of CDR H2 backbones for all HC:LC pairs with heavy chains: (A) H1-69, (B) H3-23, (C) H3-53 and (D) H5-51.	FIG
103	108	H3-53	mutant	The superposition of CDR H2 backbones for all HC:LC pairs with heavy chains: (A) H1-69, (B) H3-23, (C) H3-53 and (D) H5-51.	FIG
117	122	H5-51	mutant	The superposition of CDR H2 backbones for all HC:LC pairs with heavy chains: (A) H1-69, (B) H3-23, (C) H3-53 and (D) H5-51.	FIG
28	31	CDR	structure_element	The canonical structures of CDR H2 have fairly consistent conformations (Table 2, Fig. 2).	RESULTS
32	34	H2	structure_element	The canonical structures of CDR H2 have fairly consistent conformations (Table 2, Fig. 2).	RESULTS
14	17	HCs	structure_element	Each of the 4 HCs adopts only one canonical structure regardless of the pairing LC.	RESULTS
80	82	LC	structure_element	Each of the 4 HCs adopts only one canonical structure regardless of the pairing LC.	RESULTS
10	15	H1-69	mutant	Germlines H1-69 and H5-51 have the same canonical structure assignment H2-10-1, H3-23 has H2-10-2, and H3-53 has H2-9-3.	RESULTS
20	25	H5-51	mutant	Germlines H1-69 and H5-51 have the same canonical structure assignment H2-10-1, H3-23 has H2-10-2, and H3-53 has H2-9-3.	RESULTS
71	78	H2-10-1	mutant	Germlines H1-69 and H5-51 have the same canonical structure assignment H2-10-1, H3-23 has H2-10-2, and H3-53 has H2-9-3.	RESULTS
80	85	H3-23	mutant	Germlines H1-69 and H5-51 have the same canonical structure assignment H2-10-1, H3-23 has H2-10-2, and H3-53 has H2-9-3.	RESULTS
90	97	H2-10-2	mutant	Germlines H1-69 and H5-51 have the same canonical structure assignment H2-10-1, H3-23 has H2-10-2, and H3-53 has H2-9-3.	RESULTS
103	108	H3-53	mutant	Germlines H1-69 and H5-51 have the same canonical structure assignment H2-10-1, H3-23 has H2-10-2, and H3-53 has H2-9-3.	RESULTS
113	119	H2-9-3	mutant	Germlines H1-69 and H5-51 have the same canonical structure assignment H2-10-1, H3-23 has H2-10-2, and H3-53 has H2-9-3.	RESULTS
35	38	CDR	structure_element	The conformations for all of these CDR H2s are tightly clustered (Fig. 2).	RESULTS
39	42	H2s	structure_element	The conformations for all of these CDR H2s are tightly clustered (Fig. 2).	RESULTS
27	30	Fab	structure_element	In one case, in the second Fab of H1-69:L3-20, CDR H2 is partially disordered (Δ55-60).	RESULTS
34	45	H1-69:L3-20	complex_assembly	In one case, in the second Fab of H1-69:L3-20, CDR H2 is partially disordered (Δ55-60).	RESULTS
47	50	CDR	structure_element	In one case, in the second Fab of H1-69:L3-20, CDR H2 is partially disordered (Δ55-60).	RESULTS
51	53	H2	structure_element	In one case, in the second Fab of H1-69:L3-20, CDR H2 is partially disordered (Δ55-60).	RESULTS
57	77	partially disordered	protein_state	In one case, in the second Fab of H1-69:L3-20, CDR H2 is partially disordered (Δ55-60).	RESULTS
79	85	Δ55-60	mutant	In one case, in the second Fab of H1-69:L3-20, CDR H2 is partially disordered (Δ55-60).	RESULTS
37	40	CDR	structure_element	Although three of the germlines have CDR H2 of the same length, 10 residues, they adopt 2 distinctively different conformations depending mostly on the residue at position 71 from the so-called CDR H4.	RESULTS
41	43	H2	structure_element	Although three of the germlines have CDR H2 of the same length, 10 residues, they adopt 2 distinctively different conformations depending mostly on the residue at position 71 from the so-called CDR H4.	RESULTS
64	75	10 residues	residue_range	Although three of the germlines have CDR H2 of the same length, 10 residues, they adopt 2 distinctively different conformations depending mostly on the residue at position 71 from the so-called CDR H4.	RESULTS
172	174	71	residue_number	Although three of the germlines have CDR H2 of the same length, 10 residues, they adopt 2 distinctively different conformations depending mostly on the residue at position 71 from the so-called CDR H4.	RESULTS
194	197	CDR	structure_element	Although three of the germlines have CDR H2 of the same length, 10 residues, they adopt 2 distinctively different conformations depending mostly on the residue at position 71 from the so-called CDR H4.	RESULTS
198	200	H4	structure_element	Although three of the germlines have CDR H2 of the same length, 10 residues, they adopt 2 distinctively different conformations depending mostly on the residue at position 71 from the so-called CDR H4.	RESULTS
0	5	Arg71	residue_name_number	Arg71 in H3-23 fills the space between CDRs H2 and H4, and defines the conformation of the tip of CDR H2 so that residue 54 points away from the antigen binding site.	RESULTS
9	14	H3-23	mutant	Arg71 in H3-23 fills the space between CDRs H2 and H4, and defines the conformation of the tip of CDR H2 so that residue 54 points away from the antigen binding site.	RESULTS
39	43	CDRs	structure_element	Arg71 in H3-23 fills the space between CDRs H2 and H4, and defines the conformation of the tip of CDR H2 so that residue 54 points away from the antigen binding site.	RESULTS
44	46	H2	structure_element	Arg71 in H3-23 fills the space between CDRs H2 and H4, and defines the conformation of the tip of CDR H2 so that residue 54 points away from the antigen binding site.	RESULTS
51	53	H4	structure_element	Arg71 in H3-23 fills the space between CDRs H2 and H4, and defines the conformation of the tip of CDR H2 so that residue 54 points away from the antigen binding site.	RESULTS
98	101	CDR	structure_element	Arg71 in H3-23 fills the space between CDRs H2 and H4, and defines the conformation of the tip of CDR H2 so that residue 54 points away from the antigen binding site.	RESULTS
102	104	H2	structure_element	Arg71 in H3-23 fills the space between CDRs H2 and H4, and defines the conformation of the tip of CDR H2 so that residue 54 points away from the antigen binding site.	RESULTS
121	123	54	residue_number	Arg71 in H3-23 fills the space between CDRs H2 and H4, and defines the conformation of the tip of CDR H2 so that residue 54 points away from the antigen binding site.	RESULTS
145	165	antigen binding site	site	Arg71 in H3-23 fills the space between CDRs H2 and H4, and defines the conformation of the tip of CDR H2 so that residue 54 points away from the antigen binding site.	RESULTS
10	15	H1-69	mutant	Germlines H1-69 and H5-51 are unique in the human repertoire in having an Ala at position 71 that leaves enough space for H-Pro52a to pack deeper against CDR H4 so that the following residues 53 and 54 point toward the putative antigen.	RESULTS
20	25	H5-51	mutant	Germlines H1-69 and H5-51 are unique in the human repertoire in having an Ala at position 71 that leaves enough space for H-Pro52a to pack deeper against CDR H4 so that the following residues 53 and 54 point toward the putative antigen.	RESULTS
44	49	human	species	Germlines H1-69 and H5-51 are unique in the human repertoire in having an Ala at position 71 that leaves enough space for H-Pro52a to pack deeper against CDR H4 so that the following residues 53 and 54 point toward the putative antigen.	RESULTS
74	77	Ala	residue_name	Germlines H1-69 and H5-51 are unique in the human repertoire in having an Ala at position 71 that leaves enough space for H-Pro52a to pack deeper against CDR H4 so that the following residues 53 and 54 point toward the putative antigen.	RESULTS
90	92	71	residue_number	Germlines H1-69 and H5-51 are unique in the human repertoire in having an Ala at position 71 that leaves enough space for H-Pro52a to pack deeper against CDR H4 so that the following residues 53 and 54 point toward the putative antigen.	RESULTS
122	123	H	structure_element	Germlines H1-69 and H5-51 are unique in the human repertoire in having an Ala at position 71 that leaves enough space for H-Pro52a to pack deeper against CDR H4 so that the following residues 53 and 54 point toward the putative antigen.	RESULTS
124	130	Pro52a	residue_name_number	Germlines H1-69 and H5-51 are unique in the human repertoire in having an Ala at position 71 that leaves enough space for H-Pro52a to pack deeper against CDR H4 so that the following residues 53 and 54 point toward the putative antigen.	RESULTS
154	157	CDR	structure_element	Germlines H1-69 and H5-51 are unique in the human repertoire in having an Ala at position 71 that leaves enough space for H-Pro52a to pack deeper against CDR H4 so that the following residues 53 and 54 point toward the putative antigen.	RESULTS
158	160	H4	structure_element	Germlines H1-69 and H5-51 are unique in the human repertoire in having an Ala at position 71 that leaves enough space for H-Pro52a to pack deeper against CDR H4 so that the following residues 53 and 54 point toward the putative antigen.	RESULTS
192	194	53	residue_number	Germlines H1-69 and H5-51 are unique in the human repertoire in having an Ala at position 71 that leaves enough space for H-Pro52a to pack deeper against CDR H4 so that the following residues 53 and 54 point toward the putative antigen.	RESULTS
199	201	54	residue_number	Germlines H1-69 and H5-51 are unique in the human repertoire in having an Ala at position 71 that leaves enough space for H-Pro52a to pack deeper against CDR H4 so that the following residues 53 and 54 point toward the putative antigen.	RESULTS
17	20	CDR	structure_element	Conformations of CDR H2 in H1-69 and H5-51, both of which have canonical structure H2-10-1, show little deviation within each set of 4 structures.	RESULTS
21	23	H2	structure_element	Conformations of CDR H2 in H1-69 and H5-51, both of which have canonical structure H2-10-1, show little deviation within each set of 4 structures.	RESULTS
27	32	H1-69	mutant	Conformations of CDR H2 in H1-69 and H5-51, both of which have canonical structure H2-10-1, show little deviation within each set of 4 structures.	RESULTS
37	42	H5-51	mutant	Conformations of CDR H2 in H1-69 and H5-51, both of which have canonical structure H2-10-1, show little deviation within each set of 4 structures.	RESULTS
83	90	H2-10-1	mutant	Conformations of CDR H2 in H1-69 and H5-51, both of which have canonical structure H2-10-1, show little deviation within each set of 4 structures.	RESULTS
135	145	structures	evidence	Conformations of CDR H2 in H1-69 and H5-51, both of which have canonical structure H2-10-1, show little deviation within each set of 4 structures.	RESULTS
45	48	CDR	structure_element	However, there is a significant shift of the CDR as a rigid body when the 2 sets are superimposed.	RESULTS
85	97	superimposed	experimental_method	However, there is a significant shift of the CDR as a rigid body when the 2 sets are superimposed.	RESULTS
49	52	CDR	structure_element	Most likely this is the result of interaction of CDR H2 with CDR H1, namely with the residue at position 33 (residue 11 of 13 in CDR H1).	RESULTS
53	55	H2	structure_element	Most likely this is the result of interaction of CDR H2 with CDR H1, namely with the residue at position 33 (residue 11 of 13 in CDR H1).	RESULTS
61	64	CDR	structure_element	Most likely this is the result of interaction of CDR H2 with CDR H1, namely with the residue at position 33 (residue 11 of 13 in CDR H1).	RESULTS
65	67	H1	structure_element	Most likely this is the result of interaction of CDR H2 with CDR H1, namely with the residue at position 33 (residue 11 of 13 in CDR H1).	RESULTS
105	107	33	residue_number	Most likely this is the result of interaction of CDR H2 with CDR H1, namely with the residue at position 33 (residue 11 of 13 in CDR H1).	RESULTS
129	132	CDR	structure_element	Most likely this is the result of interaction of CDR H2 with CDR H1, namely with the residue at position 33 (residue 11 of 13 in CDR H1).	RESULTS
133	135	H1	structure_element	Most likely this is the result of interaction of CDR H2 with CDR H1, namely with the residue at position 33 (residue 11 of 13 in CDR H1).	RESULTS
9	14	H1-69	mutant	Germline H1-69 has Ala at position 33 whereas in H5-51 position 33 is occupied by a bulky Trp, which stacks against H-Tyr52 and drives CDR H2 away from the center.	RESULTS
19	22	Ala	residue_name	Germline H1-69 has Ala at position 33 whereas in H5-51 position 33 is occupied by a bulky Trp, which stacks against H-Tyr52 and drives CDR H2 away from the center.	RESULTS
35	37	33	residue_number	Germline H1-69 has Ala at position 33 whereas in H5-51 position 33 is occupied by a bulky Trp, which stacks against H-Tyr52 and drives CDR H2 away from the center.	RESULTS
49	54	H5-51	mutant	Germline H1-69 has Ala at position 33 whereas in H5-51 position 33 is occupied by a bulky Trp, which stacks against H-Tyr52 and drives CDR H2 away from the center.	RESULTS
64	66	33	residue_number	Germline H1-69 has Ala at position 33 whereas in H5-51 position 33 is occupied by a bulky Trp, which stacks against H-Tyr52 and drives CDR H2 away from the center.	RESULTS
90	93	Trp	residue_name	Germline H1-69 has Ala at position 33 whereas in H5-51 position 33 is occupied by a bulky Trp, which stacks against H-Tyr52 and drives CDR H2 away from the center.	RESULTS
116	117	H	structure_element	Germline H1-69 has Ala at position 33 whereas in H5-51 position 33 is occupied by a bulky Trp, which stacks against H-Tyr52 and drives CDR H2 away from the center.	RESULTS
118	123	Tyr52	residue_name_number	Germline H1-69 has Ala at position 33 whereas in H5-51 position 33 is occupied by a bulky Trp, which stacks against H-Tyr52 and drives CDR H2 away from the center.	RESULTS
135	138	CDR	structure_element	Germline H1-69 has Ala at position 33 whereas in H5-51 position 33 is occupied by a bulky Trp, which stacks against H-Tyr52 and drives CDR H2 away from the center.	RESULTS
139	141	H2	structure_element	Germline H1-69 has Ala at position 33 whereas in H5-51 position 33 is occupied by a bulky Trp, which stacks against H-Tyr52 and drives CDR H2 away from the center.	RESULTS
0	3	CDR	structure_element	CDR L1	RESULTS
4	6	L1	structure_element	CDR L1	RESULTS
4	17	superposition	experimental_method	The superposition of CDR L1 backbones for all HC:LC pairs with light chains: (A) L1-39, (B) L3-11, (C) L3-20 and (D) L4-1.	FIG
21	24	CDR	structure_element	The superposition of CDR L1 backbones for all HC:LC pairs with light chains: (A) L1-39, (B) L3-11, (C) L3-20 and (D) L4-1.	FIG
25	27	L1	structure_element	The superposition of CDR L1 backbones for all HC:LC pairs with light chains: (A) L1-39, (B) L3-11, (C) L3-20 and (D) L4-1.	FIG
46	51	HC:LC	complex_assembly	The superposition of CDR L1 backbones for all HC:LC pairs with light chains: (A) L1-39, (B) L3-11, (C) L3-20 and (D) L4-1.	FIG
63	75	light chains	structure_element	The superposition of CDR L1 backbones for all HC:LC pairs with light chains: (A) L1-39, (B) L3-11, (C) L3-20 and (D) L4-1.	FIG
81	86	L1-39	mutant	The superposition of CDR L1 backbones for all HC:LC pairs with light chains: (A) L1-39, (B) L3-11, (C) L3-20 and (D) L4-1.	FIG
92	97	L3-11	mutant	The superposition of CDR L1 backbones for all HC:LC pairs with light chains: (A) L1-39, (B) L3-11, (C) L3-20 and (D) L4-1.	FIG
103	108	L3-20	mutant	The superposition of CDR L1 backbones for all HC:LC pairs with light chains: (A) L1-39, (B) L3-11, (C) L3-20 and (D) L4-1.	FIG
117	121	L4-1	mutant	The superposition of CDR L1 backbones for all HC:LC pairs with light chains: (A) L1-39, (B) L3-11, (C) L3-20 and (D) L4-1.	FIG
9	11	LC	structure_element	The four LC CDRs L1 feature 3 different lengths (11, 12 and 17 residues) having a total of 4 different canonical structure assignments.	RESULTS
12	16	CDRs	structure_element	The four LC CDRs L1 feature 3 different lengths (11, 12 and 17 residues) having a total of 4 different canonical structure assignments.	RESULTS
17	19	L1	structure_element	The four LC CDRs L1 feature 3 different lengths (11, 12 and 17 residues) having a total of 4 different canonical structure assignments.	RESULTS
49	51	11	residue_range	The four LC CDRs L1 feature 3 different lengths (11, 12 and 17 residues) having a total of 4 different canonical structure assignments.	RESULTS
53	55	12	residue_range	The four LC CDRs L1 feature 3 different lengths (11, 12 and 17 residues) having a total of 4 different canonical structure assignments.	RESULTS
60	62	17	residue_range	The four LC CDRs L1 feature 3 different lengths (11, 12 and 17 residues) having a total of 4 different canonical structure assignments.	RESULTS
9	12	LCs	structure_element	Of these LCs, L1-39 and L3-11 have the same canonical structure, L1-11-1, and superimpose very well (Fig. 3A, B).	RESULTS
14	19	L1-39	mutant	Of these LCs, L1-39 and L3-11 have the same canonical structure, L1-11-1, and superimpose very well (Fig. 3A, B).	RESULTS
24	29	L3-11	mutant	Of these LCs, L1-39 and L3-11 have the same canonical structure, L1-11-1, and superimpose very well (Fig. 3A, B).	RESULTS
65	72	L1-11-1	mutant	Of these LCs, L1-39 and L3-11 have the same canonical structure, L1-11-1, and superimpose very well (Fig. 3A, B).	RESULTS
78	89	superimpose	experimental_method	Of these LCs, L1-39 and L3-11 have the same canonical structure, L1-11-1, and superimpose very well (Fig. 3A, B).	RESULTS
21	26	L3-20	mutant	For the remaining 2, L3-20 has 2 different assignments, L1-12-1 and L1-12-2, while L4-1 has a single assignment, L1-17-1.	RESULTS
56	63	L1-12-1	mutant	For the remaining 2, L3-20 has 2 different assignments, L1-12-1 and L1-12-2, while L4-1 has a single assignment, L1-17-1.	RESULTS
68	75	L1-12-2	mutant	For the remaining 2, L3-20 has 2 different assignments, L1-12-1 and L1-12-2, while L4-1 has a single assignment, L1-17-1.	RESULTS
83	87	L4-1	mutant	For the remaining 2, L3-20 has 2 different assignments, L1-12-1 and L1-12-2, while L4-1 has a single assignment, L1-17-1.	RESULTS
113	120	L1-17-1	mutant	For the remaining 2, L3-20 has 2 different assignments, L1-12-1 and L1-12-2, while L4-1 has a single assignment, L1-17-1.	RESULTS
0	4	L4-1	mutant	L4-1 has the longest CDR L1, composed of 17 amino acid residues (Fig. 3D).	RESULTS
21	24	CDR	structure_element	L4-1 has the longest CDR L1, composed of 17 amino acid residues (Fig. 3D).	RESULTS
25	27	L1	structure_element	L4-1 has the longest CDR L1, composed of 17 amino acid residues (Fig. 3D).	RESULTS
41	63	17 amino acid residues	residue_range	L4-1 has the longest CDR L1, composed of 17 amino acid residues (Fig. 3D).	RESULTS
55	59	rmsd	evidence	Despite this, the conformations are tightly clustered (rmsd is 0.20 Å).	RESULTS
34	46	stem regions	structure_element	The backbone conformations of the stem regions superimpose well.	RESULTS
52	55	30a	residue_number	Some changes in conformation occur between residues 30a and 30f (residues 8 and 13 of 17 in CDR L1).	RESULTS
60	63	30f	residue_number	Some changes in conformation occur between residues 30a and 30f (residues 8 and 13 of 17 in CDR L1).	RESULTS
74	75	8	residue_number	Some changes in conformation occur between residues 30a and 30f (residues 8 and 13 of 17 in CDR L1).	RESULTS
80	82	13	residue_number	Some changes in conformation occur between residues 30a and 30f (residues 8 and 13 of 17 in CDR L1).	RESULTS
86	88	17	residue_number	Some changes in conformation occur between residues 30a and 30f (residues 8 and 13 of 17 in CDR L1).	RESULTS
92	95	CDR	structure_element	Some changes in conformation occur between residues 30a and 30f (residues 8 and 13 of 17 in CDR L1).	RESULTS
96	98	L1	structure_element	Some changes in conformation occur between residues 30a and 30f (residues 8 and 13 of 17 in CDR L1).	RESULTS
23	34	loop region	structure_element	This is the tip of the loop region, which appears to have similar conformations that fan out the structures because of the slight differences in torsion angles in the backbone near Tyr30a and Lys30f.	RESULTS
97	107	structures	evidence	This is the tip of the loop region, which appears to have similar conformations that fan out the structures because of the slight differences in torsion angles in the backbone near Tyr30a and Lys30f.	RESULTS
181	187	Tyr30a	residue_name_number	This is the tip of the loop region, which appears to have similar conformations that fan out the structures because of the slight differences in torsion angles in the backbone near Tyr30a and Lys30f.	RESULTS
192	198	Lys30f	residue_name_number	This is the tip of the loop region, which appears to have similar conformations that fan out the structures because of the slight differences in torsion angles in the backbone near Tyr30a and Lys30f.	RESULTS
0	5	L3-20	mutant	L3-20 is the most variable in CDR L1 among the 4 germlines as indicated by an rmsd of 0.54 Å (Fig. 3C).	RESULTS
30	33	CDR	structure_element	L3-20 is the most variable in CDR L1 among the 4 germlines as indicated by an rmsd of 0.54 Å (Fig. 3C).	RESULTS
34	36	L1	structure_element	L3-20 is the most variable in CDR L1 among the 4 germlines as indicated by an rmsd of 0.54 Å (Fig. 3C).	RESULTS
78	82	rmsd	evidence	L3-20 is the most variable in CDR L1 among the 4 germlines as indicated by an rmsd of 0.54 Å (Fig. 3C).	RESULTS
4	14	structures	evidence	Two structures, H3-53:L3-20 and H5-51:L3-20 are assigned to canonical structure L1-12-1 with virtually identical backbone conformations.	RESULTS
16	27	H3-53:L3-20	complex_assembly	Two structures, H3-53:L3-20 and H5-51:L3-20 are assigned to canonical structure L1-12-1 with virtually identical backbone conformations.	RESULTS
32	43	H5-51:L3-20	complex_assembly	Two structures, H3-53:L3-20 and H5-51:L3-20 are assigned to canonical structure L1-12-1 with virtually identical backbone conformations.	RESULTS
80	87	L1-12-1	mutant	Two structures, H3-53:L3-20 and H5-51:L3-20 are assigned to canonical structure L1-12-1 with virtually identical backbone conformations.	RESULTS
21	32	H3-23:L3-20	complex_assembly	The third structure, H3-23:L3-20, has CDR L1 as L1-12-2, which deviates from L1-12-1 at residues 29-32, i.e., at the site of insertion with respect to the 11-residue CDR.	RESULTS
38	41	CDR	structure_element	The third structure, H3-23:L3-20, has CDR L1 as L1-12-2, which deviates from L1-12-1 at residues 29-32, i.e., at the site of insertion with respect to the 11-residue CDR.	RESULTS
42	44	L1	structure_element	The third structure, H3-23:L3-20, has CDR L1 as L1-12-2, which deviates from L1-12-1 at residues 29-32, i.e., at the site of insertion with respect to the 11-residue CDR.	RESULTS
48	55	L1-12-2	mutant	The third structure, H3-23:L3-20, has CDR L1 as L1-12-2, which deviates from L1-12-1 at residues 29-32, i.e., at the site of insertion with respect to the 11-residue CDR.	RESULTS
77	84	L1-12-1	mutant	The third structure, H3-23:L3-20, has CDR L1 as L1-12-2, which deviates from L1-12-1 at residues 29-32, i.e., at the site of insertion with respect to the 11-residue CDR.	RESULTS
97	102	29-32	residue_range	The third structure, H3-23:L3-20, has CDR L1 as L1-12-2, which deviates from L1-12-1 at residues 29-32, i.e., at the site of insertion with respect to the 11-residue CDR.	RESULTS
155	165	11-residue	residue_range	The third structure, H3-23:L3-20, has CDR L1 as L1-12-2, which deviates from L1-12-1 at residues 29-32, i.e., at the site of insertion with respect to the 11-residue CDR.	RESULTS
166	169	CDR	structure_element	The third structure, H3-23:L3-20, has CDR L1 as L1-12-2, which deviates from L1-12-1 at residues 29-32, i.e., at the site of insertion with respect to the 11-residue CDR.	RESULTS
30	41	H1-69:L3-20	complex_assembly	The fourth member of the set, H1-69:L3-20, was crystallized with 2 Fabs in the asymmetric unit.	RESULTS
47	59	crystallized	experimental_method	The fourth member of the set, H1-69:L3-20, was crystallized with 2 Fabs in the asymmetric unit.	RESULTS
67	71	Fabs	structure_element	The fourth member of the set, H1-69:L3-20, was crystallized with 2 Fabs in the asymmetric unit.	RESULTS
20	23	CDR	structure_element	The conformation of CDR L1 in these 2 Fabs is slightly different, and both conformations fall somewhere between L1-12-1 and L1-12-2.	RESULTS
24	26	L1	structure_element	The conformation of CDR L1 in these 2 Fabs is slightly different, and both conformations fall somewhere between L1-12-1 and L1-12-2.	RESULTS
38	42	Fabs	structure_element	The conformation of CDR L1 in these 2 Fabs is slightly different, and both conformations fall somewhere between L1-12-1 and L1-12-2.	RESULTS
112	119	L1-12-1	mutant	The conformation of CDR L1 in these 2 Fabs is slightly different, and both conformations fall somewhere between L1-12-1 and L1-12-2.	RESULTS
124	131	L1-12-2	mutant	The conformation of CDR L1 in these 2 Fabs is slightly different, and both conformations fall somewhere between L1-12-1 and L1-12-2.	RESULTS
42	51	structure	evidence	This reflects the lack of accuracy in the structure due to low resolution of the X-ray data (3.3 Å).	RESULTS
81	91	X-ray data	evidence	This reflects the lack of accuracy in the structure due to low resolution of the X-ray data (3.3 Å).	RESULTS
0	3	CDR	structure_element	CDR L2	RESULTS
4	6	L2	structure_element	CDR L2	RESULTS
4	17	superposition	experimental_method	The superposition of CDR L2 backbones for all HC:LC pairs with light chains: (A) L1-39, (B) L3-11, (C) L3-20 and (D) L4-1.	FIG
21	24	CDR	structure_element	The superposition of CDR L2 backbones for all HC:LC pairs with light chains: (A) L1-39, (B) L3-11, (C) L3-20 and (D) L4-1.	FIG
25	27	L2	structure_element	The superposition of CDR L2 backbones for all HC:LC pairs with light chains: (A) L1-39, (B) L3-11, (C) L3-20 and (D) L4-1.	FIG
46	51	HC:LC	complex_assembly	The superposition of CDR L2 backbones for all HC:LC pairs with light chains: (A) L1-39, (B) L3-11, (C) L3-20 and (D) L4-1.	FIG
63	75	light chains	structure_element	The superposition of CDR L2 backbones for all HC:LC pairs with light chains: (A) L1-39, (B) L3-11, (C) L3-20 and (D) L4-1.	FIG
81	86	L1-39	mutant	The superposition of CDR L2 backbones for all HC:LC pairs with light chains: (A) L1-39, (B) L3-11, (C) L3-20 and (D) L4-1.	FIG
92	97	L3-11	mutant	The superposition of CDR L2 backbones for all HC:LC pairs with light chains: (A) L1-39, (B) L3-11, (C) L3-20 and (D) L4-1.	FIG
103	108	L3-20	mutant	The superposition of CDR L2 backbones for all HC:LC pairs with light chains: (A) L1-39, (B) L3-11, (C) L3-20 and (D) L4-1.	FIG
117	121	L4-1	mutant	The superposition of CDR L2 backbones for all HC:LC pairs with light chains: (A) L1-39, (B) L3-11, (C) L3-20 and (D) L4-1.	FIG
9	12	LCs	structure_element	All four LCs have CDR L2 of the same length and canonical structure, L2-8-1 (Table 2).	RESULTS
18	21	CDR	structure_element	All four LCs have CDR L2 of the same length and canonical structure, L2-8-1 (Table 2).	RESULTS
22	24	L2	structure_element	All four LCs have CDR L2 of the same length and canonical structure, L2-8-1 (Table 2).	RESULTS
69	75	L2-8-1	mutant	All four LCs have CDR L2 of the same length and canonical structure, L2-8-1 (Table 2).	RESULTS
4	7	CDR	structure_element	The CDR L2 conformations for each of the LCs paired with the 4 HCs are clustered more tightly than any of the other CDRs (rmsd values are in the range 0.09-0.16 Å), and all 4 sets have virtually the same conformation despite the sequence diversity of the loop.	RESULTS
8	10	L2	structure_element	The CDR L2 conformations for each of the LCs paired with the 4 HCs are clustered more tightly than any of the other CDRs (rmsd values are in the range 0.09-0.16 Å), and all 4 sets have virtually the same conformation despite the sequence diversity of the loop.	RESULTS
41	44	LCs	structure_element	The CDR L2 conformations for each of the LCs paired with the 4 HCs are clustered more tightly than any of the other CDRs (rmsd values are in the range 0.09-0.16 Å), and all 4 sets have virtually the same conformation despite the sequence diversity of the loop.	RESULTS
63	66	HCs	structure_element	The CDR L2 conformations for each of the LCs paired with the 4 HCs are clustered more tightly than any of the other CDRs (rmsd values are in the range 0.09-0.16 Å), and all 4 sets have virtually the same conformation despite the sequence diversity of the loop.	RESULTS
116	120	CDRs	structure_element	The CDR L2 conformations for each of the LCs paired with the 4 HCs are clustered more tightly than any of the other CDRs (rmsd values are in the range 0.09-0.16 Å), and all 4 sets have virtually the same conformation despite the sequence diversity of the loop.	RESULTS
122	126	rmsd	evidence	The CDR L2 conformations for each of the LCs paired with the 4 HCs are clustered more tightly than any of the other CDRs (rmsd values are in the range 0.09-0.16 Å), and all 4 sets have virtually the same conformation despite the sequence diversity of the loop.	RESULTS
255	259	loop	structure_element	The CDR L2 conformations for each of the LCs paired with the 4 HCs are clustered more tightly than any of the other CDRs (rmsd values are in the range 0.09-0.16 Å), and all 4 sets have virtually the same conformation despite the sequence diversity of the loop.	RESULTS
0	3	CDR	structure_element	CDR L3	RESULTS
4	6	L3	structure_element	CDR L3	RESULTS
4	17	superposition	experimental_method	The superposition of CDR L3 backbones for all HC:LC pairs with light chains: (A) L1-39, (B) L3-11, (C) L3-20 and (D) L4-1.	FIG
21	24	CDR	structure_element	The superposition of CDR L3 backbones for all HC:LC pairs with light chains: (A) L1-39, (B) L3-11, (C) L3-20 and (D) L4-1.	FIG
25	27	L3	structure_element	The superposition of CDR L3 backbones for all HC:LC pairs with light chains: (A) L1-39, (B) L3-11, (C) L3-20 and (D) L4-1.	FIG
46	51	HC:LC	complex_assembly	The superposition of CDR L3 backbones for all HC:LC pairs with light chains: (A) L1-39, (B) L3-11, (C) L3-20 and (D) L4-1.	FIG
63	75	light chains	structure_element	The superposition of CDR L3 backbones for all HC:LC pairs with light chains: (A) L1-39, (B) L3-11, (C) L3-20 and (D) L4-1.	FIG
81	86	L1-39	mutant	The superposition of CDR L3 backbones for all HC:LC pairs with light chains: (A) L1-39, (B) L3-11, (C) L3-20 and (D) L4-1.	FIG
92	97	L3-11	mutant	The superposition of CDR L3 backbones for all HC:LC pairs with light chains: (A) L1-39, (B) L3-11, (C) L3-20 and (D) L4-1.	FIG
103	108	L3-20	mutant	The superposition of CDR L3 backbones for all HC:LC pairs with light chains: (A) L1-39, (B) L3-11, (C) L3-20 and (D) L4-1.	FIG
117	121	L4-1	mutant	The superposition of CDR L3 backbones for all HC:LC pairs with light chains: (A) L1-39, (B) L3-11, (C) L3-20 and (D) L4-1.	FIG
8	11	CDR	structure_element	As with CDR L2, all 4 LCs have CDR L3 of the same length and canonical structure, L3-9-cis7-1 (Table 2).	RESULTS
12	14	L2	structure_element	As with CDR L2, all 4 LCs have CDR L3 of the same length and canonical structure, L3-9-cis7-1 (Table 2).	RESULTS
22	25	LCs	structure_element	As with CDR L2, all 4 LCs have CDR L3 of the same length and canonical structure, L3-9-cis7-1 (Table 2).	RESULTS
31	34	CDR	structure_element	As with CDR L2, all 4 LCs have CDR L3 of the same length and canonical structure, L3-9-cis7-1 (Table 2).	RESULTS
35	37	L3	structure_element	As with CDR L2, all 4 LCs have CDR L3 of the same length and canonical structure, L3-9-cis7-1 (Table 2).	RESULTS
71	80	structure	evidence	As with CDR L2, all 4 LCs have CDR L3 of the same length and canonical structure, L3-9-cis7-1 (Table 2).	RESULTS
82	93	L3-9-cis7-1	mutant	As with CDR L2, all 4 LCs have CDR L3 of the same length and canonical structure, L3-9-cis7-1 (Table 2).	RESULTS
21	24	CDR	structure_element	The conformations of CDR L3 for L1-39, L3-11, and particularly for L320, are not as tightly clustered as those of L4-1 (Fig. 5).	RESULTS
25	27	L3	structure_element	The conformations of CDR L3 for L1-39, L3-11, and particularly for L320, are not as tightly clustered as those of L4-1 (Fig. 5).	RESULTS
32	37	L1-39	mutant	The conformations of CDR L3 for L1-39, L3-11, and particularly for L320, are not as tightly clustered as those of L4-1 (Fig. 5).	RESULTS
39	44	L3-11	mutant	The conformations of CDR L3 for L1-39, L3-11, and particularly for L320, are not as tightly clustered as those of L4-1 (Fig. 5).	RESULTS
114	118	L4-1	mutant	The conformations of CDR L3 for L1-39, L3-11, and particularly for L320, are not as tightly clustered as those of L4-1 (Fig. 5).	RESULTS
82	87	90-92	residue_range	The slight conformational variability occurs in the region of amino acid residues 90-92, which is in contact with CDR H3.	RESULTS
114	117	CDR	structure_element	The slight conformational variability occurs in the region of amino acid residues 90-92, which is in contact with CDR H3.	RESULTS
118	120	H3	structure_element	The slight conformational variability occurs in the region of amino acid residues 90-92, which is in contact with CDR H3.	RESULTS
0	3	CDR	structure_element	CDR H3 conformational diversity	RESULTS
4	6	H3	structure_element	CDR H3 conformational diversity	RESULTS
29	33	Fabs	structure_element	As mentioned earlier, all 16 Fabs have the same CDR H3, for which the amino acid sequence is derived from the anti-CCL2 antibody CNTO 888.	RESULTS
48	51	CDR	structure_element	As mentioned earlier, all 16 Fabs have the same CDR H3, for which the amino acid sequence is derived from the anti-CCL2 antibody CNTO 888.	RESULTS
52	54	H3	structure_element	As mentioned earlier, all 16 Fabs have the same CDR H3, for which the amino acid sequence is derived from the anti-CCL2 antibody CNTO 888.	RESULTS
120	128	antibody	protein_type	As mentioned earlier, all 16 Fabs have the same CDR H3, for which the amino acid sequence is derived from the anti-CCL2 antibody CNTO 888.	RESULTS
129	137	CNTO 888	chemical	As mentioned earlier, all 16 Fabs have the same CDR H3, for which the amino acid sequence is derived from the anti-CCL2 antibody CNTO 888.	RESULTS
4	8	loop	structure_element	The loop and the 2 β-strands of the CDR H3 in this ‘parent’ structure are stabilized by H-bonds between the carbonyl oxygen and peptide nitrogen atoms in the 2 strands.	RESULTS
19	28	β-strands	structure_element	The loop and the 2 β-strands of the CDR H3 in this ‘parent’ structure are stabilized by H-bonds between the carbonyl oxygen and peptide nitrogen atoms in the 2 strands.	RESULTS
36	39	CDR	structure_element	The loop and the 2 β-strands of the CDR H3 in this ‘parent’ structure are stabilized by H-bonds between the carbonyl oxygen and peptide nitrogen atoms in the 2 strands.	RESULTS
40	42	H3	structure_element	The loop and the 2 β-strands of the CDR H3 in this ‘parent’ structure are stabilized by H-bonds between the carbonyl oxygen and peptide nitrogen atoms in the 2 strands.	RESULTS
60	69	structure	evidence	The loop and the 2 β-strands of the CDR H3 in this ‘parent’ structure are stabilized by H-bonds between the carbonyl oxygen and peptide nitrogen atoms in the 2 strands.	RESULTS
32	35	CDR	structure_element	An interesting feature of these CDR H3 structures is the presence of a water molecule that interacts with the peptide nitrogens and carbonyl oxygens near the bridging loop connecting the 2 β-strands.	RESULTS
36	38	H3	structure_element	An interesting feature of these CDR H3 structures is the presence of a water molecule that interacts with the peptide nitrogens and carbonyl oxygens near the bridging loop connecting the 2 β-strands.	RESULTS
39	49	structures	evidence	An interesting feature of these CDR H3 structures is the presence of a water molecule that interacts with the peptide nitrogens and carbonyl oxygens near the bridging loop connecting the 2 β-strands.	RESULTS
71	76	water	chemical	An interesting feature of these CDR H3 structures is the presence of a water molecule that interacts with the peptide nitrogens and carbonyl oxygens near the bridging loop connecting the 2 β-strands.	RESULTS
167	171	loop	structure_element	An interesting feature of these CDR H3 structures is the presence of a water molecule that interacts with the peptide nitrogens and carbonyl oxygens near the bridging loop connecting the 2 β-strands.	RESULTS
189	198	β-strands	structure_element	An interesting feature of these CDR H3 structures is the presence of a water molecule that interacts with the peptide nitrogens and carbonyl oxygens near the bridging loop connecting the 2 β-strands.	RESULTS
5	10	water	chemical	This water is present in both the bound (4DN4) and unbound (4DN3) forms of CNTO 888.	RESULTS
34	39	bound	protein_state	This water is present in both the bound (4DN4) and unbound (4DN3) forms of CNTO 888.	RESULTS
51	58	unbound	protein_state	This water is present in both the bound (4DN4) and unbound (4DN3) forms of CNTO 888.	RESULTS
75	83	CNTO 888	chemical	This water is present in both the bound (4DN4) and unbound (4DN3) forms of CNTO 888.	RESULTS
4	15	stem region	structure_element	The stem region of CDR H3 in the parental Fab is in a ‘kinked’ conformation, in which the indole nitrogen of Trp103 forms a hydrogen bond with the carbonyl oxygen of Leu100b.	RESULTS
19	22	CDR	structure_element	The stem region of CDR H3 in the parental Fab is in a ‘kinked’ conformation, in which the indole nitrogen of Trp103 forms a hydrogen bond with the carbonyl oxygen of Leu100b.	RESULTS
23	25	H3	structure_element	The stem region of CDR H3 in the parental Fab is in a ‘kinked’ conformation, in which the indole nitrogen of Trp103 forms a hydrogen bond with the carbonyl oxygen of Leu100b.	RESULTS
42	45	Fab	structure_element	The stem region of CDR H3 in the parental Fab is in a ‘kinked’ conformation, in which the indole nitrogen of Trp103 forms a hydrogen bond with the carbonyl oxygen of Leu100b.	RESULTS
55	61	kinked	protein_state	The stem region of CDR H3 in the parental Fab is in a ‘kinked’ conformation, in which the indole nitrogen of Trp103 forms a hydrogen bond with the carbonyl oxygen of Leu100b.	RESULTS
109	115	Trp103	residue_name_number	The stem region of CDR H3 in the parental Fab is in a ‘kinked’ conformation, in which the indole nitrogen of Trp103 forms a hydrogen bond with the carbonyl oxygen of Leu100b.	RESULTS
166	173	Leu100b	residue_name_number	The stem region of CDR H3 in the parental Fab is in a ‘kinked’ conformation, in which the indole nitrogen of Trp103 forms a hydrogen bond with the carbonyl oxygen of Leu100b.	RESULTS
22	28	Asp101	residue_name_number	The carboxyl group of Asp101 forms a salt bridge with Arg94.	RESULTS
54	59	Arg94	residue_name_number	The carboxyl group of Asp101 forms a salt bridge with Arg94.	RESULTS
34	47	superposition	experimental_method	Ribbon representations of (A) the superposition of all CDR H3s of the structures with complete backbone traces. (B) The CDR H3s rotated 90° about the y axis of the page.	FIG
55	58	CDR	structure_element	Ribbon representations of (A) the superposition of all CDR H3s of the structures with complete backbone traces. (B) The CDR H3s rotated 90° about the y axis of the page.	FIG
59	62	H3s	structure_element	Ribbon representations of (A) the superposition of all CDR H3s of the structures with complete backbone traces. (B) The CDR H3s rotated 90° about the y axis of the page.	FIG
70	80	structures	evidence	Ribbon representations of (A) the superposition of all CDR H3s of the structures with complete backbone traces. (B) The CDR H3s rotated 90° about the y axis of the page.	FIG
120	123	CDR	structure_element	Ribbon representations of (A) the superposition of all CDR H3s of the structures with complete backbone traces. (B) The CDR H3s rotated 90° about the y axis of the page.	FIG
124	127	H3s	structure_element	Ribbon representations of (A) the superposition of all CDR H3s of the structures with complete backbone traces. (B) The CDR H3s rotated 90° about the y axis of the page.	FIG
4	13	structure	evidence	The structure of each CDR H3 is represented with a different color.	FIG
22	25	CDR	structure_element	The structure of each CDR H3 is represented with a different color.	FIG
26	28	H3	structure_element	The structure of each CDR H3 is represented with a different color.	FIG
61	64	CDR	structure_element	Despite having the same amino acid sequence in all variants, CDR H3 has the highest degree of structural diversity and disorder of all of the CDRs in the experimental set.	RESULTS
65	67	H3	structure_element	Despite having the same amino acid sequence in all variants, CDR H3 has the highest degree of structural diversity and disorder of all of the CDRs in the experimental set.	RESULTS
142	146	CDRs	structure_element	Despite having the same amino acid sequence in all variants, CDR H3 has the highest degree of structural diversity and disorder of all of the CDRs in the experimental set.	RESULTS
16	19	Fab	structure_element	Three of the 21 Fab structures (including multiple copies in the asymmetric unit), H5-51:L3-11, H551:L3-20 and H3-23:L4-1 (one of the 2 Fabs), have missing (disordered) residues at the apex of the CDR loop.	RESULTS
20	30	structures	evidence	Three of the 21 Fab structures (including multiple copies in the asymmetric unit), H5-51:L3-11, H551:L3-20 and H3-23:L4-1 (one of the 2 Fabs), have missing (disordered) residues at the apex of the CDR loop.	RESULTS
83	94	H5-51:L3-11	complex_assembly	Three of the 21 Fab structures (including multiple copies in the asymmetric unit), H5-51:L3-11, H551:L3-20 and H3-23:L4-1 (one of the 2 Fabs), have missing (disordered) residues at the apex of the CDR loop.	RESULTS
96	106	H551:L3-20	complex_assembly	Three of the 21 Fab structures (including multiple copies in the asymmetric unit), H5-51:L3-11, H551:L3-20 and H3-23:L4-1 (one of the 2 Fabs), have missing (disordered) residues at the apex of the CDR loop.	RESULTS
111	121	H3-23:L4-1	complex_assembly	Three of the 21 Fab structures (including multiple copies in the asymmetric unit), H5-51:L3-11, H551:L3-20 and H3-23:L4-1 (one of the 2 Fabs), have missing (disordered) residues at the apex of the CDR loop.	RESULTS
136	140	Fabs	structure_element	Three of the 21 Fab structures (including multiple copies in the asymmetric unit), H5-51:L3-11, H551:L3-20 and H3-23:L4-1 (one of the 2 Fabs), have missing (disordered) residues at the apex of the CDR loop.	RESULTS
148	155	missing	protein_state	Three of the 21 Fab structures (including multiple copies in the asymmetric unit), H5-51:L3-11, H551:L3-20 and H3-23:L4-1 (one of the 2 Fabs), have missing (disordered) residues at the apex of the CDR loop.	RESULTS
157	167	disordered	protein_state	Three of the 21 Fab structures (including multiple copies in the asymmetric unit), H5-51:L3-11, H551:L3-20 and H3-23:L4-1 (one of the 2 Fabs), have missing (disordered) residues at the apex of the CDR loop.	RESULTS
197	205	CDR loop	structure_element	Three of the 21 Fab structures (including multiple copies in the asymmetric unit), H5-51:L3-11, H551:L3-20 and H3-23:L4-1 (one of the 2 Fabs), have missing (disordered) residues at the apex of the CDR loop.	RESULTS
20	24	Fabs	structure_element	Another four of the Fabs, H3-23:L1-39, H3-53:L1-39, H3-53:L3-11 and H3-53:L4-1 have missing side-chain atoms.	RESULTS
26	37	H3-23:L1-39	complex_assembly	Another four of the Fabs, H3-23:L1-39, H3-53:L1-39, H3-53:L3-11 and H3-53:L4-1 have missing side-chain atoms.	RESULTS
39	50	H3-53:L1-39	complex_assembly	Another four of the Fabs, H3-23:L1-39, H3-53:L1-39, H3-53:L3-11 and H3-53:L4-1 have missing side-chain atoms.	RESULTS
52	63	H3-53:L3-11	complex_assembly	Another four of the Fabs, H3-23:L1-39, H3-53:L1-39, H3-53:L3-11 and H3-53:L4-1 have missing side-chain atoms.	RESULTS
68	78	H3-53:L4-1	complex_assembly	Another four of the Fabs, H3-23:L1-39, H3-53:L1-39, H3-53:L3-11 and H3-53:L4-1 have missing side-chain atoms.	RESULTS
18	21	CDR	structure_element	The variations in CDR H3 conformation are illustrated in Fig. 6 for the 18 Fab structures that have ordered backbone atoms.	RESULTS
22	24	H3	structure_element	The variations in CDR H3 conformation are illustrated in Fig. 6 for the 18 Fab structures that have ordered backbone atoms.	RESULTS
75	78	Fab	structure_element	The variations in CDR H3 conformation are illustrated in Fig. 6 for the 18 Fab structures that have ordered backbone atoms.	RESULTS
79	89	structures	evidence	The variations in CDR H3 conformation are illustrated in Fig. 6 for the 18 Fab structures that have ordered backbone atoms.	RESULTS
40	46	kinked	protein_state	A comparison of representatives of the “kinked” and “extended” structures.	FIG
53	61	extended	protein_state	A comparison of representatives of the “kinked” and “extended” structures.	FIG
63	73	structures	evidence	A comparison of representatives of the “kinked” and “extended” structures.	FIG
9	15	kinked	protein_state	(A) The “kinked” CDR H3 of H1-69:L3-11 with purple carbon atoms and yellow dashed lines connecting the H-bond pairs for Leu100b O and Trp103 NE1, Arg94 NE and Asp101 OD1, and Arg94 NH2 and Asp101 OD2.	FIG
17	20	CDR	structure_element	(A) The “kinked” CDR H3 of H1-69:L3-11 with purple carbon atoms and yellow dashed lines connecting the H-bond pairs for Leu100b O and Trp103 NE1, Arg94 NE and Asp101 OD1, and Arg94 NH2 and Asp101 OD2.	FIG
21	23	H3	structure_element	(A) The “kinked” CDR H3 of H1-69:L3-11 with purple carbon atoms and yellow dashed lines connecting the H-bond pairs for Leu100b O and Trp103 NE1, Arg94 NE and Asp101 OD1, and Arg94 NH2 and Asp101 OD2.	FIG
27	38	H1-69:L3-11	complex_assembly	(A) The “kinked” CDR H3 of H1-69:L3-11 with purple carbon atoms and yellow dashed lines connecting the H-bond pairs for Leu100b O and Trp103 NE1, Arg94 NE and Asp101 OD1, and Arg94 NH2 and Asp101 OD2.	FIG
120	127	Leu100b	residue_name_number	(A) The “kinked” CDR H3 of H1-69:L3-11 with purple carbon atoms and yellow dashed lines connecting the H-bond pairs for Leu100b O and Trp103 NE1, Arg94 NE and Asp101 OD1, and Arg94 NH2 and Asp101 OD2.	FIG
134	140	Trp103	residue_name_number	(A) The “kinked” CDR H3 of H1-69:L3-11 with purple carbon atoms and yellow dashed lines connecting the H-bond pairs for Leu100b O and Trp103 NE1, Arg94 NE and Asp101 OD1, and Arg94 NH2 and Asp101 OD2.	FIG
146	151	Arg94	residue_name_number	(A) The “kinked” CDR H3 of H1-69:L3-11 with purple carbon atoms and yellow dashed lines connecting the H-bond pairs for Leu100b O and Trp103 NE1, Arg94 NE and Asp101 OD1, and Arg94 NH2 and Asp101 OD2.	FIG
159	165	Asp101	residue_name_number	(A) The “kinked” CDR H3 of H1-69:L3-11 with purple carbon atoms and yellow dashed lines connecting the H-bond pairs for Leu100b O and Trp103 NE1, Arg94 NE and Asp101 OD1, and Arg94 NH2 and Asp101 OD2.	FIG
175	180	Arg94	residue_name_number	(A) The “kinked” CDR H3 of H1-69:L3-11 with purple carbon atoms and yellow dashed lines connecting the H-bond pairs for Leu100b O and Trp103 NE1, Arg94 NE and Asp101 OD1, and Arg94 NH2 and Asp101 OD2.	FIG
189	195	Asp101	residue_name_number	(A) The “kinked” CDR H3 of H1-69:L3-11 with purple carbon atoms and yellow dashed lines connecting the H-bond pairs for Leu100b O and Trp103 NE1, Arg94 NE and Asp101 OD1, and Arg94 NH2 and Asp101 OD2.	FIG
9	17	extended	protein_state	(B) The “extended” CDR H3 of H1-69:L3-20 with green carbon atoms and yellow dashed lines connecting the H-bond pairs for Asp101 OD1 and OD2 and Trp103 NE1.	FIG
19	22	CDR	structure_element	(B) The “extended” CDR H3 of H1-69:L3-20 with green carbon atoms and yellow dashed lines connecting the H-bond pairs for Asp101 OD1 and OD2 and Trp103 NE1.	FIG
23	25	H3	structure_element	(B) The “extended” CDR H3 of H1-69:L3-20 with green carbon atoms and yellow dashed lines connecting the H-bond pairs for Asp101 OD1 and OD2 and Trp103 NE1.	FIG
29	40	H1-69:L3-20	complex_assembly	(B) The “extended” CDR H3 of H1-69:L3-20 with green carbon atoms and yellow dashed lines connecting the H-bond pairs for Asp101 OD1 and OD2 and Trp103 NE1.	FIG
121	127	Asp101	residue_name_number	(B) The “extended” CDR H3 of H1-69:L3-20 with green carbon atoms and yellow dashed lines connecting the H-bond pairs for Asp101 OD1 and OD2 and Trp103 NE1.	FIG
144	150	Trp103	residue_name_number	(B) The “extended” CDR H3 of H1-69:L3-20 with green carbon atoms and yellow dashed lines connecting the H-bond pairs for Asp101 OD1 and OD2 and Trp103 NE1.	FIG
16	19	Fab	structure_element	In 10 of the 18 Fab structures, H1-69:L1-39, H1-69:L3-11 (2 Fabs), H1-69:L4-1, H3-23:L3-11 (2 Fabs), H3-23:L3-20, H3-53:L3-11, H3-53:L3-20 and H5-51:L1-39, the CDRs have similar conformations to that found in 4DN3.	RESULTS
20	30	structures	evidence	In 10 of the 18 Fab structures, H1-69:L1-39, H1-69:L3-11 (2 Fabs), H1-69:L4-1, H3-23:L3-11 (2 Fabs), H3-23:L3-20, H3-53:L3-11, H3-53:L3-20 and H5-51:L1-39, the CDRs have similar conformations to that found in 4DN3.	RESULTS
32	43	H1-69:L1-39	complex_assembly	In 10 of the 18 Fab structures, H1-69:L1-39, H1-69:L3-11 (2 Fabs), H1-69:L4-1, H3-23:L3-11 (2 Fabs), H3-23:L3-20, H3-53:L3-11, H3-53:L3-20 and H5-51:L1-39, the CDRs have similar conformations to that found in 4DN3.	RESULTS
45	56	H1-69:L3-11	complex_assembly	In 10 of the 18 Fab structures, H1-69:L1-39, H1-69:L3-11 (2 Fabs), H1-69:L4-1, H3-23:L3-11 (2 Fabs), H3-23:L3-20, H3-53:L3-11, H3-53:L3-20 and H5-51:L1-39, the CDRs have similar conformations to that found in 4DN3.	RESULTS
60	64	Fabs	structure_element	In 10 of the 18 Fab structures, H1-69:L1-39, H1-69:L3-11 (2 Fabs), H1-69:L4-1, H3-23:L3-11 (2 Fabs), H3-23:L3-20, H3-53:L3-11, H3-53:L3-20 and H5-51:L1-39, the CDRs have similar conformations to that found in 4DN3.	RESULTS
67	77	H1-69:L4-1	complex_assembly	In 10 of the 18 Fab structures, H1-69:L1-39, H1-69:L3-11 (2 Fabs), H1-69:L4-1, H3-23:L3-11 (2 Fabs), H3-23:L3-20, H3-53:L3-11, H3-53:L3-20 and H5-51:L1-39, the CDRs have similar conformations to that found in 4DN3.	RESULTS
79	90	H3-23:L3-11	complex_assembly	In 10 of the 18 Fab structures, H1-69:L1-39, H1-69:L3-11 (2 Fabs), H1-69:L4-1, H3-23:L3-11 (2 Fabs), H3-23:L3-20, H3-53:L3-11, H3-53:L3-20 and H5-51:L1-39, the CDRs have similar conformations to that found in 4DN3.	RESULTS
94	98	Fabs	structure_element	In 10 of the 18 Fab structures, H1-69:L1-39, H1-69:L3-11 (2 Fabs), H1-69:L4-1, H3-23:L3-11 (2 Fabs), H3-23:L3-20, H3-53:L3-11, H3-53:L3-20 and H5-51:L1-39, the CDRs have similar conformations to that found in 4DN3.	RESULTS
101	112	H3-23:L3-20	complex_assembly	In 10 of the 18 Fab structures, H1-69:L1-39, H1-69:L3-11 (2 Fabs), H1-69:L4-1, H3-23:L3-11 (2 Fabs), H3-23:L3-20, H3-53:L3-11, H3-53:L3-20 and H5-51:L1-39, the CDRs have similar conformations to that found in 4DN3.	RESULTS
114	125	H3-53:L3-11	complex_assembly	In 10 of the 18 Fab structures, H1-69:L1-39, H1-69:L3-11 (2 Fabs), H1-69:L4-1, H3-23:L3-11 (2 Fabs), H3-23:L3-20, H3-53:L3-11, H3-53:L3-20 and H5-51:L1-39, the CDRs have similar conformations to that found in 4DN3.	RESULTS
127	138	H3-53:L3-20	complex_assembly	In 10 of the 18 Fab structures, H1-69:L1-39, H1-69:L3-11 (2 Fabs), H1-69:L4-1, H3-23:L3-11 (2 Fabs), H3-23:L3-20, H3-53:L3-11, H3-53:L3-20 and H5-51:L1-39, the CDRs have similar conformations to that found in 4DN3.	RESULTS
143	154	H5-51:L1-39	complex_assembly	In 10 of the 18 Fab structures, H1-69:L1-39, H1-69:L3-11 (2 Fabs), H1-69:L4-1, H3-23:L3-11 (2 Fabs), H3-23:L3-20, H3-53:L3-11, H3-53:L3-20 and H5-51:L1-39, the CDRs have similar conformations to that found in 4DN3.	RESULTS
160	164	CDRs	structure_element	In 10 of the 18 Fab structures, H1-69:L1-39, H1-69:L3-11 (2 Fabs), H1-69:L4-1, H3-23:L3-11 (2 Fabs), H3-23:L3-20, H3-53:L3-11, H3-53:L3-20 and H5-51:L1-39, the CDRs have similar conformations to that found in 4DN3.	RESULTS
19	29	structures	evidence	The bases of these structures have the ‘kinked’ conformation with the H-bond between Trp103 and Leu100b.	RESULTS
40	46	kinked	protein_state	The bases of these structures have the ‘kinked’ conformation with the H-bond between Trp103 and Leu100b.	RESULTS
85	91	Trp103	residue_name_number	The bases of these structures have the ‘kinked’ conformation with the H-bond between Trp103 and Leu100b.	RESULTS
96	103	Leu100b	residue_name_number	The bases of these structures have the ‘kinked’ conformation with the H-bond between Trp103 and Leu100b.	RESULTS
17	20	CDR	structure_element	A representative CDR H3 structure for H1-69:L1-39 illustrating this is shown in Fig. 7A.	RESULTS
21	23	H3	structure_element	A representative CDR H3 structure for H1-69:L1-39 illustrating this is shown in Fig. 7A.	RESULTS
24	33	structure	evidence	A representative CDR H3 structure for H1-69:L1-39 illustrating this is shown in Fig. 7A.	RESULTS
38	49	H1-69:L1-39	complex_assembly	A representative CDR H3 structure for H1-69:L1-39 illustrating this is shown in Fig. 7A.	RESULTS
64	69	Tyr99	residue_name_number	The largest backbone conformational deviation for the set is at Tyr99, where the C=O is rotated by 90° relative to that observed in 4DN3.	RESULTS
48	58	structures	evidence	Also, it is worth noting that only one of these structures, H1-69:L4-1, has the conserved water molecule in CDR H3 observed in the 4DN3 and 4DN4 structures.	RESULTS
60	70	H1-69:L4-1	complex_assembly	Also, it is worth noting that only one of these structures, H1-69:L4-1, has the conserved water molecule in CDR H3 observed in the 4DN3 and 4DN4 structures.	RESULTS
80	89	conserved	protein_state	Also, it is worth noting that only one of these structures, H1-69:L4-1, has the conserved water molecule in CDR H3 observed in the 4DN3 and 4DN4 structures.	RESULTS
90	95	water	chemical	Also, it is worth noting that only one of these structures, H1-69:L4-1, has the conserved water molecule in CDR H3 observed in the 4DN3 and 4DN4 structures.	RESULTS
108	111	CDR	structure_element	Also, it is worth noting that only one of these structures, H1-69:L4-1, has the conserved water molecule in CDR H3 observed in the 4DN3 and 4DN4 structures.	RESULTS
112	114	H3	structure_element	Also, it is worth noting that only one of these structures, H1-69:L4-1, has the conserved water molecule in CDR H3 observed in the 4DN3 and 4DN4 structures.	RESULTS
145	155	structures	evidence	Also, it is worth noting that only one of these structures, H1-69:L4-1, has the conserved water molecule in CDR H3 observed in the 4DN3 and 4DN4 structures.	RESULTS
24	27	Fab	structure_element	In fact, it is the only Fab in the set that has a water molecule present at this site.	RESULTS
50	55	water	chemical	In fact, it is the only Fab in the set that has a water molecule present at this site.	RESULTS
4	7	CDR	structure_element	The CDR H3 for this structure is shown in Fig. S3.	RESULTS
8	10	H3	structure_element	The CDR H3 for this structure is shown in Fig. S3.	RESULTS
20	29	structure	evidence	The CDR H3 for this structure is shown in Fig. S3.	RESULTS
16	20	Fabs	structure_element	The remaining 8 Fabs can be grouped into 5 different conformational classes.	RESULTS
13	17	Fabs	structure_element	Three of the Fabs, H3-23:L1-39, H3-23:L4-1 and H3-53:L1-39, have distinctive conformations.	RESULTS
19	30	H3-23:L1-39	complex_assembly	Three of the Fabs, H3-23:L1-39, H3-23:L4-1 and H3-53:L1-39, have distinctive conformations.	RESULTS
32	42	H3-23:L4-1	complex_assembly	Three of the Fabs, H3-23:L1-39, H3-23:L4-1 and H3-53:L1-39, have distinctive conformations.	RESULTS
47	58	H3-53:L1-39	complex_assembly	Three of the Fabs, H3-23:L1-39, H3-23:L4-1 and H3-53:L1-39, have distinctive conformations.	RESULTS
4	16	stem regions	structure_element	The stem regions in these 3 cases are in the ‘kinked’ conformation consistent with that observed for 4DN3.	RESULTS
46	52	kinked	protein_state	The stem regions in these 3 cases are in the ‘kinked’ conformation consistent with that observed for 4DN3.	RESULTS
19	23	Fabs	structure_element	The five remaining Fabs, H5-51:L4-1 (2 copies), H1-69:L3-20 (2 copies) and H3-53:L4-1, have 3 different CDR H3 conformations (Fig. S4).	RESULTS
25	35	H5-51:L4-1	complex_assembly	The five remaining Fabs, H5-51:L4-1 (2 copies), H1-69:L3-20 (2 copies) and H3-53:L4-1, have 3 different CDR H3 conformations (Fig. S4).	RESULTS
48	59	H1-69:L3-20	complex_assembly	The five remaining Fabs, H5-51:L4-1 (2 copies), H1-69:L3-20 (2 copies) and H3-53:L4-1, have 3 different CDR H3 conformations (Fig. S4).	RESULTS
75	85	H3-53:L4-1	complex_assembly	The five remaining Fabs, H5-51:L4-1 (2 copies), H1-69:L3-20 (2 copies) and H3-53:L4-1, have 3 different CDR H3 conformations (Fig. S4).	RESULTS
104	107	CDR	structure_element	The five remaining Fabs, H5-51:L4-1 (2 copies), H1-69:L3-20 (2 copies) and H3-53:L4-1, have 3 different CDR H3 conformations (Fig. S4).	RESULTS
108	110	H3	structure_element	The five remaining Fabs, H5-51:L4-1 (2 copies), H1-69:L3-20 (2 copies) and H3-53:L4-1, have 3 different CDR H3 conformations (Fig. S4).	RESULTS
4	16	stem regions	structure_element	The stem regions of CDR H3 for the H5-51:L4-1 Fabs are in the ‘kinked’ conformation while, surprisingly, those of the H1-69:L3-20 pair and H3-53:L4-1 are in the ‘extended’ conformation (Fig. 7B).	RESULTS
20	23	CDR	structure_element	The stem regions of CDR H3 for the H5-51:L4-1 Fabs are in the ‘kinked’ conformation while, surprisingly, those of the H1-69:L3-20 pair and H3-53:L4-1 are in the ‘extended’ conformation (Fig. 7B).	RESULTS
24	26	H3	structure_element	The stem regions of CDR H3 for the H5-51:L4-1 Fabs are in the ‘kinked’ conformation while, surprisingly, those of the H1-69:L3-20 pair and H3-53:L4-1 are in the ‘extended’ conformation (Fig. 7B).	RESULTS
35	45	H5-51:L4-1	complex_assembly	The stem regions of CDR H3 for the H5-51:L4-1 Fabs are in the ‘kinked’ conformation while, surprisingly, those of the H1-69:L3-20 pair and H3-53:L4-1 are in the ‘extended’ conformation (Fig. 7B).	RESULTS
46	50	Fabs	structure_element	The stem regions of CDR H3 for the H5-51:L4-1 Fabs are in the ‘kinked’ conformation while, surprisingly, those of the H1-69:L3-20 pair and H3-53:L4-1 are in the ‘extended’ conformation (Fig. 7B).	RESULTS
63	69	kinked	protein_state	The stem regions of CDR H3 for the H5-51:L4-1 Fabs are in the ‘kinked’ conformation while, surprisingly, those of the H1-69:L3-20 pair and H3-53:L4-1 are in the ‘extended’ conformation (Fig. 7B).	RESULTS
118	129	H1-69:L3-20	complex_assembly	The stem regions of CDR H3 for the H5-51:L4-1 Fabs are in the ‘kinked’ conformation while, surprisingly, those of the H1-69:L3-20 pair and H3-53:L4-1 are in the ‘extended’ conformation (Fig. 7B).	RESULTS
139	149	H3-53:L4-1	complex_assembly	The stem regions of CDR H3 for the H5-51:L4-1 Fabs are in the ‘kinked’ conformation while, surprisingly, those of the H1-69:L3-20 pair and H3-53:L4-1 are in the ‘extended’ conformation (Fig. 7B).	RESULTS
162	170	extended	protein_state	The stem regions of CDR H3 for the H5-51:L4-1 Fabs are in the ‘kinked’ conformation while, surprisingly, those of the H1-69:L3-20 pair and H3-53:L4-1 are in the ‘extended’ conformation (Fig. 7B).	RESULTS
0	5	VH:VL	complex_assembly	VH:VL domain packing	RESULTS
4	6	VH	structure_element	The VH and VL domains have a β-sandwich structure (also often referred as a Greek key motif) and each is composed of a 4-stranded and a 5-stranded antiparallel β-sheets.	RESULTS
11	13	VL	structure_element	The VH and VL domains have a β-sandwich structure (also often referred as a Greek key motif) and each is composed of a 4-stranded and a 5-stranded antiparallel β-sheets.	RESULTS
29	49	β-sandwich structure	structure_element	The VH and VL domains have a β-sandwich structure (also often referred as a Greek key motif) and each is composed of a 4-stranded and a 5-stranded antiparallel β-sheets.	RESULTS
76	91	Greek key motif	structure_element	The VH and VL domains have a β-sandwich structure (also often referred as a Greek key motif) and each is composed of a 4-stranded and a 5-stranded antiparallel β-sheets.	RESULTS
119	168	4-stranded and a 5-stranded antiparallel β-sheets	structure_element	The VH and VL domains have a β-sandwich structure (also often referred as a Greek key motif) and each is composed of a 4-stranded and a 5-stranded antiparallel β-sheets.	RESULTS
44	63	5-stranded β-sheets	structure_element	The two domains pack together such that the 5-stranded β-sheets, which have hydrophobic surfaces, interact with each other bringing the CDRs from both the VH and VL domains into close proximity.	RESULTS
136	140	CDRs	structure_element	The two domains pack together such that the 5-stranded β-sheets, which have hydrophobic surfaces, interact with each other bringing the CDRs from both the VH and VL domains into close proximity.	RESULTS
155	157	VH	structure_element	The two domains pack together such that the 5-stranded β-sheets, which have hydrophobic surfaces, interact with each other bringing the CDRs from both the VH and VL domains into close proximity.	RESULTS
162	164	VL	structure_element	The two domains pack together such that the 5-stranded β-sheets, which have hydrophobic surfaces, interact with each other bringing the CDRs from both the VH and VL domains into close proximity.	RESULTS
65	81	domain interface	site	The domain packing of the variants was assessed by computing the domain interface interactions, the VH:VL tilt angles, the buried surface area and surface complementarity.	RESULTS
100	105	VH:VL	complex_assembly	The domain packing of the variants was assessed by computing the domain interface interactions, the VH:VL tilt angles, the buried surface area and surface complementarity.	RESULTS
106	117	tilt angles	evidence	The domain packing of the variants was assessed by computing the domain interface interactions, the VH:VL tilt angles, the buried surface area and surface complementarity.	RESULTS
0	15	VH:VL interface	site	VH:VL interface amino acid residue interactions	RESULTS
4	13	conserved	protein_state	The conserved VH:VL interactions as viewed along the VH/VL axis.	FIG
14	19	VH:VL	complex_assembly	The conserved VH:VL interactions as viewed along the VH/VL axis.	FIG
53	55	VH	structure_element	The conserved VH:VL interactions as viewed along the VH/VL axis.	FIG
56	58	VL	structure_element	The conserved VH:VL interactions as viewed along the VH/VL axis.	FIG
4	6	VH	structure_element	The VH residues are in blue, the VL residues are in orange.	FIG
33	35	VL	structure_element	The VH residues are in blue, the VL residues are in orange.	FIG
4	19	VH:VL interface	site	The VH:VL interface is pseudosymmetric, and involves 2 stretches of the polypeptide chain from each domain, namely CDR3 and the framework region between CDRs 1 and 2.	RESULTS
23	38	pseudosymmetric	protein_state	The VH:VL interface is pseudosymmetric, and involves 2 stretches of the polypeptide chain from each domain, namely CDR3 and the framework region between CDRs 1 and 2.	RESULTS
115	119	CDR3	structure_element	The VH:VL interface is pseudosymmetric, and involves 2 stretches of the polypeptide chain from each domain, namely CDR3 and the framework region between CDRs 1 and 2.	RESULTS
128	144	framework region	structure_element	The VH:VL interface is pseudosymmetric, and involves 2 stretches of the polypeptide chain from each domain, namely CDR3 and the framework region between CDRs 1 and 2.	RESULTS
153	165	CDRs 1 and 2	structure_element	The VH:VL interface is pseudosymmetric, and involves 2 stretches of the polypeptide chain from each domain, namely CDR3 and the framework region between CDRs 1 and 2.	RESULTS
21	44	antiparallel β-hairpins	structure_element	These stretches form antiparallel β-hairpins within the internal 5-stranded β-sheet.	RESULTS
65	83	5-stranded β-sheet	structure_element	These stretches form antiparallel β-hairpins within the internal 5-stranded β-sheet.	RESULTS
110	114	Fabs	structure_element	There are a few principal inter-domain interactions that are conserved not only in the experimental set of 16 Fabs, but in all human antibodies.	RESULTS
127	132	human	species	There are a few principal inter-domain interactions that are conserved not only in the experimental set of 16 Fabs, but in all human antibodies.	RESULTS
133	143	antibodies	protein_type	There are a few principal inter-domain interactions that are conserved not only in the experimental set of 16 Fabs, but in all human antibodies.	RESULTS
51	52	L	structure_element	They include: 1) a bidentate hydrogen bond between L-Gln38 and H-Gln39; 2) H-Leu45 in a hydrophobic pocket between L-Phe98, L-Tyr87 and L-Pro44; 3) L-Pro44 stacked against H-Trp103; and 4) L-Ala43 opposite the face of H-Tyr91 (Fig. 8).	RESULTS
53	58	Gln38	residue_name_number	They include: 1) a bidentate hydrogen bond between L-Gln38 and H-Gln39; 2) H-Leu45 in a hydrophobic pocket between L-Phe98, L-Tyr87 and L-Pro44; 3) L-Pro44 stacked against H-Trp103; and 4) L-Ala43 opposite the face of H-Tyr91 (Fig. 8).	RESULTS
63	64	H	structure_element	They include: 1) a bidentate hydrogen bond between L-Gln38 and H-Gln39; 2) H-Leu45 in a hydrophobic pocket between L-Phe98, L-Tyr87 and L-Pro44; 3) L-Pro44 stacked against H-Trp103; and 4) L-Ala43 opposite the face of H-Tyr91 (Fig. 8).	RESULTS
65	70	Gln39	residue_name_number	They include: 1) a bidentate hydrogen bond between L-Gln38 and H-Gln39; 2) H-Leu45 in a hydrophobic pocket between L-Phe98, L-Tyr87 and L-Pro44; 3) L-Pro44 stacked against H-Trp103; and 4) L-Ala43 opposite the face of H-Tyr91 (Fig. 8).	RESULTS
75	76	H	structure_element	They include: 1) a bidentate hydrogen bond between L-Gln38 and H-Gln39; 2) H-Leu45 in a hydrophobic pocket between L-Phe98, L-Tyr87 and L-Pro44; 3) L-Pro44 stacked against H-Trp103; and 4) L-Ala43 opposite the face of H-Tyr91 (Fig. 8).	RESULTS
77	82	Leu45	residue_name_number	They include: 1) a bidentate hydrogen bond between L-Gln38 and H-Gln39; 2) H-Leu45 in a hydrophobic pocket between L-Phe98, L-Tyr87 and L-Pro44; 3) L-Pro44 stacked against H-Trp103; and 4) L-Ala43 opposite the face of H-Tyr91 (Fig. 8).	RESULTS
88	106	hydrophobic pocket	site	They include: 1) a bidentate hydrogen bond between L-Gln38 and H-Gln39; 2) H-Leu45 in a hydrophobic pocket between L-Phe98, L-Tyr87 and L-Pro44; 3) L-Pro44 stacked against H-Trp103; and 4) L-Ala43 opposite the face of H-Tyr91 (Fig. 8).	RESULTS
115	116	L	structure_element	They include: 1) a bidentate hydrogen bond between L-Gln38 and H-Gln39; 2) H-Leu45 in a hydrophobic pocket between L-Phe98, L-Tyr87 and L-Pro44; 3) L-Pro44 stacked against H-Trp103; and 4) L-Ala43 opposite the face of H-Tyr91 (Fig. 8).	RESULTS
117	122	Phe98	residue_name_number	They include: 1) a bidentate hydrogen bond between L-Gln38 and H-Gln39; 2) H-Leu45 in a hydrophobic pocket between L-Phe98, L-Tyr87 and L-Pro44; 3) L-Pro44 stacked against H-Trp103; and 4) L-Ala43 opposite the face of H-Tyr91 (Fig. 8).	RESULTS
124	125	L	structure_element	They include: 1) a bidentate hydrogen bond between L-Gln38 and H-Gln39; 2) H-Leu45 in a hydrophobic pocket between L-Phe98, L-Tyr87 and L-Pro44; 3) L-Pro44 stacked against H-Trp103; and 4) L-Ala43 opposite the face of H-Tyr91 (Fig. 8).	RESULTS
126	131	Tyr87	residue_name_number	They include: 1) a bidentate hydrogen bond between L-Gln38 and H-Gln39; 2) H-Leu45 in a hydrophobic pocket between L-Phe98, L-Tyr87 and L-Pro44; 3) L-Pro44 stacked against H-Trp103; and 4) L-Ala43 opposite the face of H-Tyr91 (Fig. 8).	RESULTS
136	137	L	structure_element	They include: 1) a bidentate hydrogen bond between L-Gln38 and H-Gln39; 2) H-Leu45 in a hydrophobic pocket between L-Phe98, L-Tyr87 and L-Pro44; 3) L-Pro44 stacked against H-Trp103; and 4) L-Ala43 opposite the face of H-Tyr91 (Fig. 8).	RESULTS
138	143	Pro44	residue_name_number	They include: 1) a bidentate hydrogen bond between L-Gln38 and H-Gln39; 2) H-Leu45 in a hydrophobic pocket between L-Phe98, L-Tyr87 and L-Pro44; 3) L-Pro44 stacked against H-Trp103; and 4) L-Ala43 opposite the face of H-Tyr91 (Fig. 8).	RESULTS
148	149	L	structure_element	They include: 1) a bidentate hydrogen bond between L-Gln38 and H-Gln39; 2) H-Leu45 in a hydrophobic pocket between L-Phe98, L-Tyr87 and L-Pro44; 3) L-Pro44 stacked against H-Trp103; and 4) L-Ala43 opposite the face of H-Tyr91 (Fig. 8).	RESULTS
150	155	Pro44	residue_name_number	They include: 1) a bidentate hydrogen bond between L-Gln38 and H-Gln39; 2) H-Leu45 in a hydrophobic pocket between L-Phe98, L-Tyr87 and L-Pro44; 3) L-Pro44 stacked against H-Trp103; and 4) L-Ala43 opposite the face of H-Tyr91 (Fig. 8).	RESULTS
172	173	H	structure_element	They include: 1) a bidentate hydrogen bond between L-Gln38 and H-Gln39; 2) H-Leu45 in a hydrophobic pocket between L-Phe98, L-Tyr87 and L-Pro44; 3) L-Pro44 stacked against H-Trp103; and 4) L-Ala43 opposite the face of H-Tyr91 (Fig. 8).	RESULTS
174	180	Trp103	residue_name_number	They include: 1) a bidentate hydrogen bond between L-Gln38 and H-Gln39; 2) H-Leu45 in a hydrophobic pocket between L-Phe98, L-Tyr87 and L-Pro44; 3) L-Pro44 stacked against H-Trp103; and 4) L-Ala43 opposite the face of H-Tyr91 (Fig. 8).	RESULTS
189	190	L	structure_element	They include: 1) a bidentate hydrogen bond between L-Gln38 and H-Gln39; 2) H-Leu45 in a hydrophobic pocket between L-Phe98, L-Tyr87 and L-Pro44; 3) L-Pro44 stacked against H-Trp103; and 4) L-Ala43 opposite the face of H-Tyr91 (Fig. 8).	RESULTS
191	196	Ala43	residue_name_number	They include: 1) a bidentate hydrogen bond between L-Gln38 and H-Gln39; 2) H-Leu45 in a hydrophobic pocket between L-Phe98, L-Tyr87 and L-Pro44; 3) L-Pro44 stacked against H-Trp103; and 4) L-Ala43 opposite the face of H-Tyr91 (Fig. 8).	RESULTS
218	219	H	structure_element	They include: 1) a bidentate hydrogen bond between L-Gln38 and H-Gln39; 2) H-Leu45 in a hydrophobic pocket between L-Phe98, L-Tyr87 and L-Pro44; 3) L-Pro44 stacked against H-Trp103; and 4) L-Ala43 opposite the face of H-Tyr91 (Fig. 8).	RESULTS
220	225	Tyr91	residue_name_number	They include: 1) a bidentate hydrogen bond between L-Gln38 and H-Gln39; 2) H-Leu45 in a hydrophobic pocket between L-Phe98, L-Tyr87 and L-Pro44; 3) L-Pro44 stacked against H-Trp103; and 4) L-Ala43 opposite the face of H-Tyr91 (Fig. 8).	RESULTS
22	23	L	structure_element	With the exception of L-Ala43, all other residues are conserved in human germlines.	RESULTS
24	29	Ala43	residue_name_number	With the exception of L-Ala43, all other residues are conserved in human germlines.	RESULTS
67	72	human	species	With the exception of L-Ala43, all other residues are conserved in human germlines.	RESULTS
9	11	43	residue_number	Position 43 may be alternatively occupied by Ser, Val or Pro (as in L4-1), but the hydrophobic interaction with H-Tyr91 is preserved.	RESULTS
45	48	Ser	residue_name	Position 43 may be alternatively occupied by Ser, Val or Pro (as in L4-1), but the hydrophobic interaction with H-Tyr91 is preserved.	RESULTS
50	53	Val	residue_name	Position 43 may be alternatively occupied by Ser, Val or Pro (as in L4-1), but the hydrophobic interaction with H-Tyr91 is preserved.	RESULTS
57	60	Pro	residue_name	Position 43 may be alternatively occupied by Ser, Val or Pro (as in L4-1), but the hydrophobic interaction with H-Tyr91 is preserved.	RESULTS
68	72	L4-1	mutant	Position 43 may be alternatively occupied by Ser, Val or Pro (as in L4-1), but the hydrophobic interaction with H-Tyr91 is preserved.	RESULTS
112	113	H	structure_element	Position 43 may be alternatively occupied by Ser, Val or Pro (as in L4-1), but the hydrophobic interaction with H-Tyr91 is preserved.	RESULTS
114	119	Tyr91	residue_name_number	Position 43 may be alternatively occupied by Ser, Val or Pro (as in L4-1), but the hydrophobic interaction with H-Tyr91 is preserved.	RESULTS
56	61	VH:VL	complex_assembly	These core interactions provide enough stability to the VH:VL dimer so that additional VH-VL contacts can tolerate amino acid sequence variations in CDRs H3 and L3 that form part of the VH:VL interface.	RESULTS
62	67	dimer	oligomeric_state	These core interactions provide enough stability to the VH:VL dimer so that additional VH-VL contacts can tolerate amino acid sequence variations in CDRs H3 and L3 that form part of the VH:VL interface.	RESULTS
87	101	VH-VL contacts	site	These core interactions provide enough stability to the VH:VL dimer so that additional VH-VL contacts can tolerate amino acid sequence variations in CDRs H3 and L3 that form part of the VH:VL interface.	RESULTS
149	153	CDRs	structure_element	These core interactions provide enough stability to the VH:VL dimer so that additional VH-VL contacts can tolerate amino acid sequence variations in CDRs H3 and L3 that form part of the VH:VL interface.	RESULTS
154	156	H3	structure_element	These core interactions provide enough stability to the VH:VL dimer so that additional VH-VL contacts can tolerate amino acid sequence variations in CDRs H3 and L3 that form part of the VH:VL interface.	RESULTS
161	163	L3	structure_element	These core interactions provide enough stability to the VH:VL dimer so that additional VH-VL contacts can tolerate amino acid sequence variations in CDRs H3 and L3 that form part of the VH:VL interface.	RESULTS
186	201	VH:VL interface	site	These core interactions provide enough stability to the VH:VL dimer so that additional VH-VL contacts can tolerate amino acid sequence variations in CDRs H3 and L3 that form part of the VH:VL interface.	RESULTS
16	27	20 residues	residue_range	In total, about 20 residues are involved in the VH:VL interactions on each side (Fig. S5).	RESULTS
48	53	VH:VL	complex_assembly	In total, about 20 residues are involved in the VH:VL interactions on each side (Fig. S5).	RESULTS
24	41	framework regions	structure_element	Half of them are in the framework regions and those residues (except residue 61 in HC, which is actually in CDR2 in Kabat's definition) are conserved in the set of 16 Fabs.	RESULTS
77	79	61	residue_number	Half of them are in the framework regions and those residues (except residue 61 in HC, which is actually in CDR2 in Kabat's definition) are conserved in the set of 16 Fabs.	RESULTS
83	85	HC	structure_element	Half of them are in the framework regions and those residues (except residue 61 in HC, which is actually in CDR2 in Kabat's definition) are conserved in the set of 16 Fabs.	RESULTS
108	112	CDR2	structure_element	Half of them are in the framework regions and those residues (except residue 61 in HC, which is actually in CDR2 in Kabat's definition) are conserved in the set of 16 Fabs.	RESULTS
167	171	Fabs	structure_element	Half of them are in the framework regions and those residues (except residue 61 in HC, which is actually in CDR2 in Kabat's definition) are conserved in the set of 16 Fabs.	RESULTS
25	26	H	structure_element	One notable exception is H-Trp47, which exhibits 2 conformations of the indole ring.	RESULTS
27	32	Trp47	residue_name_number	One notable exception is H-Trp47, which exhibits 2 conformations of the indole ring.	RESULTS
15	25	structures	evidence	In most of the structures, it has the χ2 angle of ∼80°, while the ring is flipped over (χ2 = −100°) in H5-51:L3:11 and H5-51:L3-20.	RESULTS
38	40	χ2	evidence	In most of the structures, it has the χ2 angle of ∼80°, while the ring is flipped over (χ2 = −100°) in H5-51:L3:11 and H5-51:L3-20.	RESULTS
88	90	χ2	evidence	In most of the structures, it has the χ2 angle of ∼80°, while the ring is flipped over (χ2 = −100°) in H5-51:L3:11 and H5-51:L3-20.	RESULTS
103	114	H5-51:L3:11	complex_assembly	In most of the structures, it has the χ2 angle of ∼80°, while the ring is flipped over (χ2 = −100°) in H5-51:L3:11 and H5-51:L3-20.	RESULTS
119	130	H5-51:L3-20	complex_assembly	In most of the structures, it has the χ2 angle of ∼80°, while the ring is flipped over (χ2 = −100°) in H5-51:L3:11 and H5-51:L3-20.	RESULTS
36	46	structures	evidence	Interestingly, these are the only 2 structures with residues missing in CDR H3 because of disorder, although both structures are determined at high resolution and the rest of the structure is well defined.	RESULTS
61	68	missing	protein_state	Interestingly, these are the only 2 structures with residues missing in CDR H3 because of disorder, although both structures are determined at high resolution and the rest of the structure is well defined.	RESULTS
72	75	CDR	structure_element	Interestingly, these are the only 2 structures with residues missing in CDR H3 because of disorder, although both structures are determined at high resolution and the rest of the structure is well defined.	RESULTS
76	78	H3	structure_element	Interestingly, these are the only 2 structures with residues missing in CDR H3 because of disorder, although both structures are determined at high resolution and the rest of the structure is well defined.	RESULTS
114	124	structures	evidence	Interestingly, these are the only 2 structures with residues missing in CDR H3 because of disorder, although both structures are determined at high resolution and the rest of the structure is well defined.	RESULTS
179	188	structure	evidence	Interestingly, these are the only 2 structures with residues missing in CDR H3 because of disorder, although both structures are determined at high resolution and the rest of the structure is well defined.	RESULTS
30	33	CDR	structure_element	Apparently, residues flanking CDR H3 in the 2 VH:VL pairings are inconsistent with any stable conformation of CDR H3, which translates into a less restricted conformational space for some of them, including H-Trp47.	RESULTS
34	36	H3	structure_element	Apparently, residues flanking CDR H3 in the 2 VH:VL pairings are inconsistent with any stable conformation of CDR H3, which translates into a less restricted conformational space for some of them, including H-Trp47.	RESULTS
46	51	VH:VL	complex_assembly	Apparently, residues flanking CDR H3 in the 2 VH:VL pairings are inconsistent with any stable conformation of CDR H3, which translates into a less restricted conformational space for some of them, including H-Trp47.	RESULTS
87	93	stable	protein_state	Apparently, residues flanking CDR H3 in the 2 VH:VL pairings are inconsistent with any stable conformation of CDR H3, which translates into a less restricted conformational space for some of them, including H-Trp47.	RESULTS
110	113	CDR	structure_element	Apparently, residues flanking CDR H3 in the 2 VH:VL pairings are inconsistent with any stable conformation of CDR H3, which translates into a less restricted conformational space for some of them, including H-Trp47.	RESULTS
114	116	H3	structure_element	Apparently, residues flanking CDR H3 in the 2 VH:VL pairings are inconsistent with any stable conformation of CDR H3, which translates into a less restricted conformational space for some of them, including H-Trp47.	RESULTS
207	208	H	structure_element	Apparently, residues flanking CDR H3 in the 2 VH:VL pairings are inconsistent with any stable conformation of CDR H3, which translates into a less restricted conformational space for some of them, including H-Trp47.	RESULTS
209	214	Trp47	residue_name_number	Apparently, residues flanking CDR H3 in the 2 VH:VL pairings are inconsistent with any stable conformation of CDR H3, which translates into a less restricted conformational space for some of them, including H-Trp47.	RESULTS
0	5	VH:VL	complex_assembly	VH:VL tilt angles	RESULTS
6	17	tilt angles	evidence	VH:VL tilt angles	RESULTS
28	30	VH	structure_element	The relative orientation of VH and VL has been measured in a number of different ways.	RESULTS
35	37	VL	structure_element	The relative orientation of VH and VL has been measured in a number of different ways.	RESULTS
24	32	ABangles	experimental_method	The first approach uses ABangles, the results of which are shown in Table S2.	RESULTS
9	12	LCs	structure_element	The four LCs all are classified as Type A because they have a proline at position 44, and the results for each orientation parameter are within the range of values of this type reported by Dunbar and co-workers.	RESULTS
62	69	proline	residue_name	The four LCs all are classified as Type A because they have a proline at position 44, and the results for each orientation parameter are within the range of values of this type reported by Dunbar and co-workers.	RESULTS
82	84	44	residue_number	The four LCs all are classified as Type A because they have a proline at position 44, and the results for each orientation parameter are within the range of values of this type reported by Dunbar and co-workers.	RESULTS
111	132	orientation parameter	evidence	The four LCs all are classified as Type A because they have a proline at position 44, and the results for each orientation parameter are within the range of values of this type reported by Dunbar and co-workers.	RESULTS
48	52	Fabs	structure_element	In fact, the parameter values for the set of 16 Fabs are in the middle of the distribution observed for 351 non-redundant antibody structures determined at 3.0 Å resolution or better.	RESULTS
122	130	antibody	protein_type	In fact, the parameter values for the set of 16 Fabs are in the middle of the distribution observed for 351 non-redundant antibody structures determined at 3.0 Å resolution or better.	RESULTS
131	141	structures	evidence	In fact, the parameter values for the set of 16 Fabs are in the middle of the distribution observed for 351 non-redundant antibody structures determined at 3.0 Å resolution or better.	RESULTS
22	25	HC1	structure_element	The only exception is HC1, which is shifted toward smaller angles with the mean value of 70.8° as compared to the distribution centered at 72° for the entire PDB.	RESULTS
41	44	CDR	structure_element	This probably reflects the invariance of CDR H3 in the current set as opposed to the CDR H3 diversity in the PDB.	RESULTS
45	47	H3	structure_element	This probably reflects the invariance of CDR H3 in the current set as opposed to the CDR H3 diversity in the PDB.	RESULTS
85	88	CDR	structure_element	This probably reflects the invariance of CDR H3 in the current set as opposed to the CDR H3 diversity in the PDB.	RESULTS
89	91	H3	structure_element	This probably reflects the invariance of CDR H3 in the current set as opposed to the CDR H3 diversity in the PDB.	RESULTS
39	50	tilt angles	evidence	The second approach used for comparing tilt angles involved computing the difference in the tilt angles between all pairs of structures.	RESULTS
74	84	difference	evidence	The second approach used for comparing tilt angles involved computing the difference in the tilt angles between all pairs of structures.	RESULTS
92	103	tilt angles	evidence	The second approach used for comparing tilt angles involved computing the difference in the tilt angles between all pairs of structures.	RESULTS
125	135	structures	evidence	The second approach used for comparing tilt angles involved computing the difference in the tilt angles between all pairs of structures.	RESULTS
4	14	structures	evidence	For structures with 2 copies of the Fab in the asymmetric unit, only one structure was used.	RESULTS
36	39	Fab	structure_element	For structures with 2 copies of the Fab in the asymmetric unit, only one structure was used.	RESULTS
73	82	structure	evidence	For structures with 2 copies of the Fab in the asymmetric unit, only one structure was used.	RESULTS
36	40	Fabs	structure_element	The differences between independent Fabs in the same structure are 4.9° for H1-69:L3-20, 1.6° for H1-69:L3-11, 1.4° for H3-23:L4-1, 3.3° for H3-23:L3-11, and 2.5° for H5-51:L4-1.	RESULTS
53	62	structure	evidence	The differences between independent Fabs in the same structure are 4.9° for H1-69:L3-20, 1.6° for H1-69:L3-11, 1.4° for H3-23:L4-1, 3.3° for H3-23:L3-11, and 2.5° for H5-51:L4-1.	RESULTS
76	87	H1-69:L3-20	complex_assembly	The differences between independent Fabs in the same structure are 4.9° for H1-69:L3-20, 1.6° for H1-69:L3-11, 1.4° for H3-23:L4-1, 3.3° for H3-23:L3-11, and 2.5° for H5-51:L4-1.	RESULTS
98	109	H1-69:L3-11	complex_assembly	The differences between independent Fabs in the same structure are 4.9° for H1-69:L3-20, 1.6° for H1-69:L3-11, 1.4° for H3-23:L4-1, 3.3° for H3-23:L3-11, and 2.5° for H5-51:L4-1.	RESULTS
120	130	H3-23:L4-1	complex_assembly	The differences between independent Fabs in the same structure are 4.9° for H1-69:L3-20, 1.6° for H1-69:L3-11, 1.4° for H3-23:L4-1, 3.3° for H3-23:L3-11, and 2.5° for H5-51:L4-1.	RESULTS
141	152	H3-23:L3-11	complex_assembly	The differences between independent Fabs in the same structure are 4.9° for H1-69:L3-20, 1.6° for H1-69:L3-11, 1.4° for H3-23:L4-1, 3.3° for H3-23:L3-11, and 2.5° for H5-51:L4-1.	RESULTS
167	177	H5-51:L4-1	complex_assembly	The differences between independent Fabs in the same structure are 4.9° for H1-69:L3-20, 1.6° for H1-69:L3-11, 1.4° for H3-23:L4-1, 3.3° for H3-23:L3-11, and 2.5° for H5-51:L4-1.	RESULTS
22	33	H1-69:L3-20	complex_assembly	With the exception of H1-69:L3-20, the angles are within the range of 2-3° as are observed in the identical structures in the PDB.	RESULTS
108	118	structures	evidence	With the exception of H1-69:L3-20, the angles are within the range of 2-3° as are observed in the identical structures in the PDB.	RESULTS
3	14	H1-69:L3-20	complex_assembly	In H1-69:L3-20, one of the Fabs is substantially disordered so that part of CDR H2 (the outer β-strand, residues 55-60) is completely missing.	RESULTS
27	31	Fabs	structure_element	In H1-69:L3-20, one of the Fabs is substantially disordered so that part of CDR H2 (the outer β-strand, residues 55-60) is completely missing.	RESULTS
49	59	disordered	protein_state	In H1-69:L3-20, one of the Fabs is substantially disordered so that part of CDR H2 (the outer β-strand, residues 55-60) is completely missing.	RESULTS
76	79	CDR	structure_element	In H1-69:L3-20, one of the Fabs is substantially disordered so that part of CDR H2 (the outer β-strand, residues 55-60) is completely missing.	RESULTS
80	82	H2	structure_element	In H1-69:L3-20, one of the Fabs is substantially disordered so that part of CDR H2 (the outer β-strand, residues 55-60) is completely missing.	RESULTS
94	102	β-strand	structure_element	In H1-69:L3-20, one of the Fabs is substantially disordered so that part of CDR H2 (the outer β-strand, residues 55-60) is completely missing.	RESULTS
113	118	55-60	residue_range	In H1-69:L3-20, one of the Fabs is substantially disordered so that part of CDR H2 (the outer β-strand, residues 55-60) is completely missing.	RESULTS
58	60	VH	structure_element	This kind of disorder may compromise the integrity of the VH domain and its interaction with the VL.	RESULTS
97	99	VL	structure_element	This kind of disorder may compromise the integrity of the VH domain and its interaction with the VL.	RESULTS
13	16	Fab	structure_element	Indeed, this Fab has the largest twist angle HC2 within the experimental set that exceeds the mean value by 2.5 standard deviations (Table S2).	RESULTS
33	44	twist angle	evidence	Indeed, this Fab has the largest twist angle HC2 within the experimental set that exceeds the mean value by 2.5 standard deviations (Table S2).	RESULTS
45	48	HC2	structure_element	Indeed, this Fab has the largest twist angle HC2 within the experimental set that exceeds the mean value by 2.5 standard deviations (Table S2).	RESULTS
79	92	superposition	experimental_method	An illustration of the difference in tilt angle for 2 pairs of variants by the superposition of the VH domains of (A) H1-69:L3-20 on that of H5-51:L1-39 (the VL domain is off by a rigid-body roatation of 10.5°) and (B) H1-69:L4-1 on that of H5-51:L1-39 (the VL domain is off by a rigid-body roatation of 1.6°).	FIG
100	102	VH	structure_element	An illustration of the difference in tilt angle for 2 pairs of variants by the superposition of the VH domains of (A) H1-69:L3-20 on that of H5-51:L1-39 (the VL domain is off by a rigid-body roatation of 10.5°) and (B) H1-69:L4-1 on that of H5-51:L1-39 (the VL domain is off by a rigid-body roatation of 1.6°).	FIG
118	129	H1-69:L3-20	complex_assembly	An illustration of the difference in tilt angle for 2 pairs of variants by the superposition of the VH domains of (A) H1-69:L3-20 on that of H5-51:L1-39 (the VL domain is off by a rigid-body roatation of 10.5°) and (B) H1-69:L4-1 on that of H5-51:L1-39 (the VL domain is off by a rigid-body roatation of 1.6°).	FIG
141	152	H5-51:L1-39	complex_assembly	An illustration of the difference in tilt angle for 2 pairs of variants by the superposition of the VH domains of (A) H1-69:L3-20 on that of H5-51:L1-39 (the VL domain is off by a rigid-body roatation of 10.5°) and (B) H1-69:L4-1 on that of H5-51:L1-39 (the VL domain is off by a rigid-body roatation of 1.6°).	FIG
158	160	VL	structure_element	An illustration of the difference in tilt angle for 2 pairs of variants by the superposition of the VH domains of (A) H1-69:L3-20 on that of H5-51:L1-39 (the VL domain is off by a rigid-body roatation of 10.5°) and (B) H1-69:L4-1 on that of H5-51:L1-39 (the VL domain is off by a rigid-body roatation of 1.6°).	FIG
219	229	H1-69:L4-1	complex_assembly	An illustration of the difference in tilt angle for 2 pairs of variants by the superposition of the VH domains of (A) H1-69:L3-20 on that of H5-51:L1-39 (the VL domain is off by a rigid-body roatation of 10.5°) and (B) H1-69:L4-1 on that of H5-51:L1-39 (the VL domain is off by a rigid-body roatation of 1.6°).	FIG
241	252	H5-51:L1-39	complex_assembly	An illustration of the difference in tilt angle for 2 pairs of variants by the superposition of the VH domains of (A) H1-69:L3-20 on that of H5-51:L1-39 (the VL domain is off by a rigid-body roatation of 10.5°) and (B) H1-69:L4-1 on that of H5-51:L1-39 (the VL domain is off by a rigid-body roatation of 1.6°).	FIG
258	260	VL	structure_element	An illustration of the difference in tilt angle for 2 pairs of variants by the superposition of the VH domains of (A) H1-69:L3-20 on that of H5-51:L1-39 (the VL domain is off by a rigid-body roatation of 10.5°) and (B) H1-69:L4-1 on that of H5-51:L1-39 (the VL domain is off by a rigid-body roatation of 1.6°).	FIG
15	20	VH:VL	complex_assembly	Differences in VH:VL tilt angles.	TABLE
21	32	tilt angles	evidence	Differences in VH:VL tilt angles.	TABLE
4	15	differences	evidence	The differences in the tilt angle are shown for all pairs of V regions in Table 3.	RESULTS
23	33	tilt angle	evidence	The differences in the tilt angle are shown for all pairs of V regions in Table 3.	RESULTS
61	70	V regions	structure_element	The differences in the tilt angle are shown for all pairs of V regions in Table 3.	RESULTS
32	42	tilt angle	evidence	The smallest differences in the tilt angle are between the Fabs in isomorphous crystal forms.	RESULTS
59	63	Fabs	structure_element	The smallest differences in the tilt angle are between the Fabs in isomorphous crystal forms.	RESULTS
79	92	crystal forms	evidence	The smallest differences in the tilt angle are between the Fabs in isomorphous crystal forms.	RESULTS
30	40	tilt angle	evidence	The largest deviations in the tilt angle, up to 11.0°, are found for 2 structures, H1-69:L3-20 and H3-23:L3-20, that stand out from the other Fabs.	RESULTS
71	81	structures	evidence	The largest deviations in the tilt angle, up to 11.0°, are found for 2 structures, H1-69:L3-20 and H3-23:L3-20, that stand out from the other Fabs.	RESULTS
83	94	H1-69:L3-20	complex_assembly	The largest deviations in the tilt angle, up to 11.0°, are found for 2 structures, H1-69:L3-20 and H3-23:L3-20, that stand out from the other Fabs.	RESULTS
99	110	H3-23:L3-20	complex_assembly	The largest deviations in the tilt angle, up to 11.0°, are found for 2 structures, H1-69:L3-20 and H3-23:L3-20, that stand out from the other Fabs.	RESULTS
142	146	Fabs	structure_element	The largest deviations in the tilt angle, up to 11.0°, are found for 2 structures, H1-69:L3-20 and H3-23:L3-20, that stand out from the other Fabs.	RESULTS
13	23	structures	evidence	One of the 2 structures, H1-69:L3-20, has its CDR H3 in the ‘extended’ conformation; the other structure has it in the ‘kinked’ conformation.	RESULTS
25	36	H1-69:L3-20	complex_assembly	One of the 2 structures, H1-69:L3-20, has its CDR H3 in the ‘extended’ conformation; the other structure has it in the ‘kinked’ conformation.	RESULTS
46	49	CDR	structure_element	One of the 2 structures, H1-69:L3-20, has its CDR H3 in the ‘extended’ conformation; the other structure has it in the ‘kinked’ conformation.	RESULTS
50	52	H3	structure_element	One of the 2 structures, H1-69:L3-20, has its CDR H3 in the ‘extended’ conformation; the other structure has it in the ‘kinked’ conformation.	RESULTS
61	69	extended	protein_state	One of the 2 structures, H1-69:L3-20, has its CDR H3 in the ‘extended’ conformation; the other structure has it in the ‘kinked’ conformation.	RESULTS
120	126	kinked	protein_state	One of the 2 structures, H1-69:L3-20, has its CDR H3 in the ‘extended’ conformation; the other structure has it in the ‘kinked’ conformation.	RESULTS
76	87	tilt angles	evidence	Two examples illustrating large (10.5°) and small (1.6°) differences in the tilt angles are shown in Fig. 9.	RESULTS
0	5	VH:VL	complex_assembly	VH:VL buried surface area and complementarity	RESULTS
0	5	VH:VL	complex_assembly	VH:VL surface areas and surface complementarity.	TABLE
25	28	CDR	structure_element	Some side chain atoms in CDR H3 are missing.	TABLE
29	31	H3	structure_element	Some side chain atoms in CDR H3 are missing.	TABLE
12	15	CDR	structure_element	Residues in CDR H3 are missing: YGE in H5-51:L3-11, GIY in H5-51:L3-20.	TABLE
16	18	H3	structure_element	Residues in CDR H3 are missing: YGE in H5-51:L3-11, GIY in H5-51:L3-20.	TABLE
32	35	YGE	structure_element	Residues in CDR H3 are missing: YGE in H5-51:L3-11, GIY in H5-51:L3-20.	TABLE
39	50	H5-51:L3-11	complex_assembly	Residues in CDR H3 are missing: YGE in H5-51:L3-11, GIY in H5-51:L3-20.	TABLE
52	55	GIY	structure_element	Residues in CDR H3 are missing: YGE in H5-51:L3-11, GIY in H5-51:L3-20.	TABLE
59	70	H5-51:L3-20	complex_assembly	Residues in CDR H3 are missing: YGE in H5-51:L3-11, GIY in H5-51:L3-20.	TABLE
19	23	PISA	experimental_method	The results of the PISA contact surface calculation and surface complementarity calculation are shown in Table 4.	RESULTS
24	51	contact surface calculation	experimental_method	The results of the PISA contact surface calculation and surface complementarity calculation are shown in Table 4.	RESULTS
56	91	surface complementarity calculation	experimental_method	The results of the PISA contact surface calculation and surface complementarity calculation are shown in Table 4.	RESULTS
4	13	interface	site	The interface areas are calculated as the average of the VH and VL contact surfaces.	RESULTS
57	83	VH and VL contact surfaces	site	The interface areas are calculated as the average of the VH and VL contact surfaces.	RESULTS
14	24	structures	evidence	Six of the 16 structures have CDR H3 side chains or complete residues missing, and therefore their interfaces are much smaller than in the other 10 structures with complete CDRs (the results are provided for all Fabs for completeness).	RESULTS
30	33	CDR	structure_element	Six of the 16 structures have CDR H3 side chains or complete residues missing, and therefore their interfaces are much smaller than in the other 10 structures with complete CDRs (the results are provided for all Fabs for completeness).	RESULTS
34	36	H3	structure_element	Six of the 16 structures have CDR H3 side chains or complete residues missing, and therefore their interfaces are much smaller than in the other 10 structures with complete CDRs (the results are provided for all Fabs for completeness).	RESULTS
70	77	missing	protein_state	Six of the 16 structures have CDR H3 side chains or complete residues missing, and therefore their interfaces are much smaller than in the other 10 structures with complete CDRs (the results are provided for all Fabs for completeness).	RESULTS
99	109	interfaces	site	Six of the 16 structures have CDR H3 side chains or complete residues missing, and therefore their interfaces are much smaller than in the other 10 structures with complete CDRs (the results are provided for all Fabs for completeness).	RESULTS
148	158	structures	evidence	Six of the 16 structures have CDR H3 side chains or complete residues missing, and therefore their interfaces are much smaller than in the other 10 structures with complete CDRs (the results are provided for all Fabs for completeness).	RESULTS
164	172	complete	protein_state	Six of the 16 structures have CDR H3 side chains or complete residues missing, and therefore their interfaces are much smaller than in the other 10 structures with complete CDRs (the results are provided for all Fabs for completeness).	RESULTS
173	177	CDRs	structure_element	Six of the 16 structures have CDR H3 side chains or complete residues missing, and therefore their interfaces are much smaller than in the other 10 structures with complete CDRs (the results are provided for all Fabs for completeness).	RESULTS
212	216	Fabs	structure_element	Six of the 16 structures have CDR H3 side chains or complete residues missing, and therefore their interfaces are much smaller than in the other 10 structures with complete CDRs (the results are provided for all Fabs for completeness).	RESULTS
10	18	complete	protein_state	Among the complete structures, the interface areas range from 684 to 836 Å2.	RESULTS
19	29	structures	evidence	Among the complete structures, the interface areas range from 684 to 836 Å2.	RESULTS
35	44	interface	site	Among the complete structures, the interface areas range from 684 to 836 Å2.	RESULTS
21	31	structures	evidence	Interestingly, the 2 structures that have the largest tilt angle differences with the other variants, H3-23:L3-20 and H1-69:L3-20, have the smallest VH:VL interfaces, 684 and 725 Å2, respectively.	RESULTS
54	76	tilt angle differences	evidence	Interestingly, the 2 structures that have the largest tilt angle differences with the other variants, H3-23:L3-20 and H1-69:L3-20, have the smallest VH:VL interfaces, 684 and 725 Å2, respectively.	RESULTS
102	113	H3-23:L3-20	complex_assembly	Interestingly, the 2 structures that have the largest tilt angle differences with the other variants, H3-23:L3-20 and H1-69:L3-20, have the smallest VH:VL interfaces, 684 and 725 Å2, respectively.	RESULTS
118	129	H1-69:L3-20	complex_assembly	Interestingly, the 2 structures that have the largest tilt angle differences with the other variants, H3-23:L3-20 and H1-69:L3-20, have the smallest VH:VL interfaces, 684 and 725 Å2, respectively.	RESULTS
149	165	VH:VL interfaces	site	Interestingly, the 2 structures that have the largest tilt angle differences with the other variants, H3-23:L3-20 and H1-69:L3-20, have the smallest VH:VL interfaces, 684 and 725 Å2, respectively.	RESULTS
0	11	H3-23:L3-20	complex_assembly	H3-23:L3-20 is also unique in that it has the lowest value (0.676) of surface complementarity.	RESULTS
70	93	surface complementarity	evidence	H3-23:L3-20 is also unique in that it has the lowest value (0.676) of surface complementarity.	RESULTS
0	20	Melting temperatures	evidence	Melting temperatures for the 16 Fabs.	TABLE
32	36	Fabs	structure_element	Melting temperatures for the 16 Fabs.	TABLE
14	16	Tm	evidence	Colors: blue (Tm < 70°C), green (70°C < Tm < 73°C), yellow (73°C < Tm < 78°C), orange (Tm > 78°C).	TABLE
40	42	Tm	evidence	Colors: blue (Tm < 70°C), green (70°C < Tm < 73°C), yellow (73°C < Tm < 78°C), orange (Tm > 78°C).	TABLE
67	69	Tm	evidence	Colors: blue (Tm < 70°C), green (70°C < Tm < 73°C), yellow (73°C < Tm < 78°C), orange (Tm > 78°C).	TABLE
87	89	Tm	evidence	Colors: blue (Tm < 70°C), green (70°C < Tm < 73°C), yellow (73°C < Tm < 78°C), orange (Tm > 78°C).	TABLE
0	20	Melting temperatures	evidence	Melting temperatures (Tm) were measured for all Fabs using differential scanning calorimetry (Table 5).	RESULTS
22	24	Tm	evidence	Melting temperatures (Tm) were measured for all Fabs using differential scanning calorimetry (Table 5).	RESULTS
48	52	Fabs	structure_element	Melting temperatures (Tm) were measured for all Fabs using differential scanning calorimetry (Table 5).	RESULTS
59	92	differential scanning calorimetry	experimental_method	Melting temperatures (Tm) were measured for all Fabs using differential scanning calorimetry (Table 5).	RESULTS
31	33	LC	structure_element	It appears that for each given LC, the Fabs with germlines H1-69 and H3-23 are substantially more stable than those with germlines H3-53 and H5-51.	RESULTS
39	43	Fabs	structure_element	It appears that for each given LC, the Fabs with germlines H1-69 and H3-23 are substantially more stable than those with germlines H3-53 and H5-51.	RESULTS
59	64	H1-69	mutant	It appears that for each given LC, the Fabs with germlines H1-69 and H3-23 are substantially more stable than those with germlines H3-53 and H5-51.	RESULTS
69	74	H3-23	mutant	It appears that for each given LC, the Fabs with germlines H1-69 and H3-23 are substantially more stable than those with germlines H3-53 and H5-51.	RESULTS
98	104	stable	protein_state	It appears that for each given LC, the Fabs with germlines H1-69 and H3-23 are substantially more stable than those with germlines H3-53 and H5-51.	RESULTS
131	136	H3-53	mutant	It appears that for each given LC, the Fabs with germlines H1-69 and H3-23 are substantially more stable than those with germlines H3-53 and H5-51.	RESULTS
141	146	H5-51	mutant	It appears that for each given LC, the Fabs with germlines H1-69 and H3-23 are substantially more stable than those with germlines H3-53 and H5-51.	RESULTS
13	18	L1-39	mutant	In addition, L1-39 provides a much higher degree of stabilization than the other 3 LC germlines when combined with any of the HCs.	RESULTS
83	85	LC	structure_element	In addition, L1-39 provides a much higher degree of stabilization than the other 3 LC germlines when combined with any of the HCs.	RESULTS
126	129	HCs	structure_element	In addition, L1-39 provides a much higher degree of stabilization than the other 3 LC germlines when combined with any of the HCs.	RESULTS
17	19	Tm	evidence	As a result, the Tm for pairs H1-69:L1-39 and H3-23:L1-39 is 12-13° higher than for pairs H3-53:L3-20, H3-53:L4-1, H5-51:L3-20 and H5-51:L4-1.	RESULTS
30	41	H1-69:L1-39	complex_assembly	As a result, the Tm for pairs H1-69:L1-39 and H3-23:L1-39 is 12-13° higher than for pairs H3-53:L3-20, H3-53:L4-1, H5-51:L3-20 and H5-51:L4-1.	RESULTS
46	57	H3-23:L1-39	complex_assembly	As a result, the Tm for pairs H1-69:L1-39 and H3-23:L1-39 is 12-13° higher than for pairs H3-53:L3-20, H3-53:L4-1, H5-51:L3-20 and H5-51:L4-1.	RESULTS
90	101	H3-53:L3-20	complex_assembly	As a result, the Tm for pairs H1-69:L1-39 and H3-23:L1-39 is 12-13° higher than for pairs H3-53:L3-20, H3-53:L4-1, H5-51:L3-20 and H5-51:L4-1.	RESULTS
103	113	H3-53:L4-1	complex_assembly	As a result, the Tm for pairs H1-69:L1-39 and H3-23:L1-39 is 12-13° higher than for pairs H3-53:L3-20, H3-53:L4-1, H5-51:L3-20 and H5-51:L4-1.	RESULTS
115	126	H5-51:L3-20	complex_assembly	As a result, the Tm for pairs H1-69:L1-39 and H3-23:L1-39 is 12-13° higher than for pairs H3-53:L3-20, H3-53:L4-1, H5-51:L3-20 and H5-51:L4-1.	RESULTS
131	141	H5-51:L4-1	complex_assembly	As a result, the Tm for pairs H1-69:L1-39 and H3-23:L1-39 is 12-13° higher than for pairs H3-53:L3-20, H3-53:L4-1, H5-51:L3-20 and H5-51:L4-1.	RESULTS
89	107	crystal structures	evidence	These findings correlate well with the degree of conformational disorder observed in the crystal structures.	RESULTS
9	12	CDR	structure_element	Parts of CDR H3 main chain are completely disordered, and were not modeled in Fabs H5-51:L3-20 and H5-51:L3-11 that have the lowest Tms in the set.	RESULTS
13	15	H3	structure_element	Parts of CDR H3 main chain are completely disordered, and were not modeled in Fabs H5-51:L3-20 and H5-51:L3-11 that have the lowest Tms in the set.	RESULTS
42	52	disordered	protein_state	Parts of CDR H3 main chain are completely disordered, and were not modeled in Fabs H5-51:L3-20 and H5-51:L3-11 that have the lowest Tms in the set.	RESULTS
78	82	Fabs	structure_element	Parts of CDR H3 main chain are completely disordered, and were not modeled in Fabs H5-51:L3-20 and H5-51:L3-11 that have the lowest Tms in the set.	RESULTS
83	94	H5-51:L3-20	complex_assembly	Parts of CDR H3 main chain are completely disordered, and were not modeled in Fabs H5-51:L3-20 and H5-51:L3-11 that have the lowest Tms in the set.	RESULTS
99	110	H5-51:L3-11	complex_assembly	Parts of CDR H3 main chain are completely disordered, and were not modeled in Fabs H5-51:L3-20 and H5-51:L3-11 that have the lowest Tms in the set.	RESULTS
132	135	Tms	evidence	Parts of CDR H3 main chain are completely disordered, and were not modeled in Fabs H5-51:L3-20 and H5-51:L3-11 that have the lowest Tms in the set.	RESULTS
3	19	electron density	evidence	No electron density is observed for a number of side chains in CDRs H3 and L3 in all Fabs with germline H3-53, which indicates loose packing of the variable domains.	RESULTS
63	67	CDRs	structure_element	No electron density is observed for a number of side chains in CDRs H3 and L3 in all Fabs with germline H3-53, which indicates loose packing of the variable domains.	RESULTS
68	70	H3	structure_element	No electron density is observed for a number of side chains in CDRs H3 and L3 in all Fabs with germline H3-53, which indicates loose packing of the variable domains.	RESULTS
75	77	L3	structure_element	No electron density is observed for a number of side chains in CDRs H3 and L3 in all Fabs with germline H3-53, which indicates loose packing of the variable domains.	RESULTS
85	89	Fabs	structure_element	No electron density is observed for a number of side chains in CDRs H3 and L3 in all Fabs with germline H3-53, which indicates loose packing of the variable domains.	RESULTS
104	109	H3-53	mutant	No electron density is observed for a number of side chains in CDRs H3 and L3 in all Fabs with germline H3-53, which indicates loose packing of the variable domains.	RESULTS
148	164	variable domains	structure_element	No electron density is observed for a number of side chains in CDRs H3 and L3 in all Fabs with germline H3-53, which indicates loose packing of the variable domains.	RESULTS
74	77	Tms	evidence	All those molecules are relatively unstable, as is reflected in their low Tms.	RESULTS
30	65	systematic structural investigation	experimental_method	This is the first report of a systematic structural investigation of a phage germline library.	DISCUSS
71	93	phage germline library	experimental_method	This is the first report of a systematic structural investigation of a phage germline library.	DISCUSS
7	10	Fab	structure_element	The 16 Fab structures offer a unique look at all pairings of 4 different HCs (H1-69, H3-23, H3-53, and H5-51) and 4 different LCs (L1-39, L3-11, L3-20 and L4-1), all with the same CDR H3.	DISCUSS
11	21	structures	evidence	The 16 Fab structures offer a unique look at all pairings of 4 different HCs (H1-69, H3-23, H3-53, and H5-51) and 4 different LCs (L1-39, L3-11, L3-20 and L4-1), all with the same CDR H3.	DISCUSS
73	76	HCs	structure_element	The 16 Fab structures offer a unique look at all pairings of 4 different HCs (H1-69, H3-23, H3-53, and H5-51) and 4 different LCs (L1-39, L3-11, L3-20 and L4-1), all with the same CDR H3.	DISCUSS
78	83	H1-69	mutant	The 16 Fab structures offer a unique look at all pairings of 4 different HCs (H1-69, H3-23, H3-53, and H5-51) and 4 different LCs (L1-39, L3-11, L3-20 and L4-1), all with the same CDR H3.	DISCUSS
85	90	H3-23	mutant	The 16 Fab structures offer a unique look at all pairings of 4 different HCs (H1-69, H3-23, H3-53, and H5-51) and 4 different LCs (L1-39, L3-11, L3-20 and L4-1), all with the same CDR H3.	DISCUSS
92	97	H3-53	mutant	The 16 Fab structures offer a unique look at all pairings of 4 different HCs (H1-69, H3-23, H3-53, and H5-51) and 4 different LCs (L1-39, L3-11, L3-20 and L4-1), all with the same CDR H3.	DISCUSS
103	108	H5-51	mutant	The 16 Fab structures offer a unique look at all pairings of 4 different HCs (H1-69, H3-23, H3-53, and H5-51) and 4 different LCs (L1-39, L3-11, L3-20 and L4-1), all with the same CDR H3.	DISCUSS
126	129	LCs	structure_element	The 16 Fab structures offer a unique look at all pairings of 4 different HCs (H1-69, H3-23, H3-53, and H5-51) and 4 different LCs (L1-39, L3-11, L3-20 and L4-1), all with the same CDR H3.	DISCUSS
131	136	L1-39	mutant	The 16 Fab structures offer a unique look at all pairings of 4 different HCs (H1-69, H3-23, H3-53, and H5-51) and 4 different LCs (L1-39, L3-11, L3-20 and L4-1), all with the same CDR H3.	DISCUSS
138	143	L3-11	mutant	The 16 Fab structures offer a unique look at all pairings of 4 different HCs (H1-69, H3-23, H3-53, and H5-51) and 4 different LCs (L1-39, L3-11, L3-20 and L4-1), all with the same CDR H3.	DISCUSS
145	150	L3-20	mutant	The 16 Fab structures offer a unique look at all pairings of 4 different HCs (H1-69, H3-23, H3-53, and H5-51) and 4 different LCs (L1-39, L3-11, L3-20 and L4-1), all with the same CDR H3.	DISCUSS
155	159	L4-1	mutant	The 16 Fab structures offer a unique look at all pairings of 4 different HCs (H1-69, H3-23, H3-53, and H5-51) and 4 different LCs (L1-39, L3-11, L3-20 and L4-1), all with the same CDR H3.	DISCUSS
180	183	CDR	structure_element	The 16 Fab structures offer a unique look at all pairings of 4 different HCs (H1-69, H3-23, H3-53, and H5-51) and 4 different LCs (L1-39, L3-11, L3-20 and L4-1), all with the same CDR H3.	DISCUSS
184	186	H3	structure_element	The 16 Fab structures offer a unique look at all pairings of 4 different HCs (H1-69, H3-23, H3-53, and H5-51) and 4 different LCs (L1-39, L3-11, L3-20 and L4-1), all with the same CDR H3.	DISCUSS
4	19	structural data	evidence	The structural data set taken as a whole provides insight into how the backbone conformations of the CDRs of a specific heavy or light chain vary when it is paired with 4 different light or heavy chains, respectively.	DISCUSS
101	105	CDRs	structure_element	The structural data set taken as a whole provides insight into how the backbone conformations of the CDRs of a specific heavy or light chain vary when it is paired with 4 different light or heavy chains, respectively.	DISCUSS
129	140	light chain	structure_element	The structural data set taken as a whole provides insight into how the backbone conformations of the CDRs of a specific heavy or light chain vary when it is paired with 4 different light or heavy chains, respectively.	DISCUSS
190	202	heavy chains	structure_element	The structural data set taken as a whole provides insight into how the backbone conformations of the CDRs of a specific heavy or light chain vary when it is paired with 4 different light or heavy chains, respectively.	DISCUSS
27	30	CDR	structure_element	A large variability in the CDR conformations for the sets of HCs and LCs is observed.	DISCUSS
61	64	HCs	structure_element	A large variability in the CDR conformations for the sets of HCs and LCs is observed.	DISCUSS
69	72	LCs	structure_element	A large variability in the CDR conformations for the sets of HCs and LCs is observed.	DISCUSS
18	21	CDR	structure_element	In some cases the CDR conformations for all members of a set are virtually identical, for others subtle changes occur in a few members of a set, and in some cases larger deviations are observed within a set.	DISCUSS
23	35	crystallized	experimental_method	The five variants that crystallized with 2 copies of the Fab in the asymmetric unit serve somewhat as controls for the influence of crystal packing on the conformations of the CDRs.	DISCUSS
57	60	Fab	structure_element	The five variants that crystallized with 2 copies of the Fab in the asymmetric unit serve somewhat as controls for the influence of crystal packing on the conformations of the CDRs.	DISCUSS
176	180	CDRs	structure_element	The five variants that crystallized with 2 copies of the Fab in the asymmetric unit serve somewhat as controls for the influence of crystal packing on the conformations of the CDRs.	DISCUSS
17	27	structures	evidence	In four of the 5 structures the CDR conformations are consistent.	DISCUSS
32	35	CDR	structure_element	In four of the 5 structures the CDR conformations are consistent.	DISCUSS
26	37	H1-69:L3-20	complex_assembly	In only one case, that of H1-69:L3-20 (the lowest resolution structure), do we see differences in the conformations of the 2 copies of CDRs H1 and L1.	DISCUSS
61	70	structure	evidence	In only one case, that of H1-69:L3-20 (the lowest resolution structure), do we see differences in the conformations of the 2 copies of CDRs H1 and L1.	DISCUSS
135	139	CDRs	structure_element	In only one case, that of H1-69:L3-20 (the lowest resolution structure), do we see differences in the conformations of the 2 copies of CDRs H1 and L1.	DISCUSS
140	142	H1	structure_element	In only one case, that of H1-69:L3-20 (the lowest resolution structure), do we see differences in the conformations of the 2 copies of CDRs H1 and L1.	DISCUSS
147	149	L1	structure_element	In only one case, that of H1-69:L3-20 (the lowest resolution structure), do we see differences in the conformations of the 2 copies of CDRs H1 and L1.	DISCUSS
111	126	variable domain	structure_element	This variability is likely a result of 2 factors, crystal packing interactions and internal instability of the variable domain.	DISCUSS
8	12	CDRs	structure_element	For the CDRs with canonical structures, the largest changes in conformation occur for CDR H1 of H1-69 and H3-53.	DISCUSS
86	89	CDR	structure_element	For the CDRs with canonical structures, the largest changes in conformation occur for CDR H1 of H1-69 and H3-53.	DISCUSS
90	92	H1	structure_element	For the CDRs with canonical structures, the largest changes in conformation occur for CDR H1 of H1-69 and H3-53.	DISCUSS
96	101	H1-69	mutant	For the CDRs with canonical structures, the largest changes in conformation occur for CDR H1 of H1-69 and H3-53.	DISCUSS
106	111	H3-53	mutant	For the CDRs with canonical structures, the largest changes in conformation occur for CDR H1 of H1-69 and H3-53.	DISCUSS
12	15	HCs	structure_element	The other 2 HCs, H3-23 and H5-51, have canonical structures that are remarkably well conserved (Fig. 1).	DISCUSS
17	22	H3-23	mutant	The other 2 HCs, H3-23 and H5-51, have canonical structures that are remarkably well conserved (Fig. 1).	DISCUSS
27	32	H5-51	mutant	The other 2 HCs, H3-23 and H5-51, have canonical structures that are remarkably well conserved (Fig. 1).	DISCUSS
69	94	remarkably well conserved	protein_state	The other 2 HCs, H3-23 and H5-51, have canonical structures that are remarkably well conserved (Fig. 1).	DISCUSS
9	12	HCs	structure_element	Of the 4 HCs, H1-69 has the greatest number of canonical structure assignments (Table 2).	DISCUSS
14	19	H1-69	mutant	Of the 4 HCs, H1-69 has the greatest number of canonical structure assignments (Table 2).	DISCUSS
0	5	H1-69	mutant	H1-69 is unique in having a pair of glycine residues at positions 26 and 27, which provide more conformational freedom in CDR H1.	DISCUSS
36	43	glycine	residue_name	H1-69 is unique in having a pair of glycine residues at positions 26 and 27, which provide more conformational freedom in CDR H1.	DISCUSS
66	68	26	residue_number	H1-69 is unique in having a pair of glycine residues at positions 26 and 27, which provide more conformational freedom in CDR H1.	DISCUSS
73	75	27	residue_number	H1-69 is unique in having a pair of glycine residues at positions 26 and 27, which provide more conformational freedom in CDR H1.	DISCUSS
96	118	conformational freedom	protein_state	H1-69 is unique in having a pair of glycine residues at positions 26 and 27, which provide more conformational freedom in CDR H1.	DISCUSS
122	125	CDR	structure_element	H1-69 is unique in having a pair of glycine residues at positions 26 and 27, which provide more conformational freedom in CDR H1.	DISCUSS
126	128	H1	structure_element	H1-69 is unique in having a pair of glycine residues at positions 26 and 27, which provide more conformational freedom in CDR H1.	DISCUSS
8	16	IGHV1-69	mutant	Besides IGHV1-69, only the germlines of the VH4 family possess double glycines in CDR H1, and it will be interesting to see if they are also conformationally unstable.	DISCUSS
44	47	VH4	structure_element	Besides IGHV1-69, only the germlines of the VH4 family possess double glycines in CDR H1, and it will be interesting to see if they are also conformationally unstable.	DISCUSS
70	78	glycines	residue_name	Besides IGHV1-69, only the germlines of the VH4 family possess double glycines in CDR H1, and it will be interesting to see if they are also conformationally unstable.	DISCUSS
82	85	CDR	structure_element	Besides IGHV1-69, only the germlines of the VH4 family possess double glycines in CDR H1, and it will be interesting to see if they are also conformationally unstable.	DISCUSS
86	88	H1	structure_element	Besides IGHV1-69, only the germlines of the VH4 family possess double glycines in CDR H1, and it will be interesting to see if they are also conformationally unstable.	DISCUSS
141	166	conformationally unstable	protein_state	Besides IGHV1-69, only the germlines of the VH4 family possess double glycines in CDR H1, and it will be interesting to see if they are also conformationally unstable.	DISCUSS
14	19	VH:VL	complex_assembly	Having all 16 VH:VL pairs with the same CDR H3 provides some insights into why molecular modeling efforts of CDR H3 have proven so difficult.	DISCUSS
40	43	CDR	structure_element	Having all 16 VH:VL pairs with the same CDR H3 provides some insights into why molecular modeling efforts of CDR H3 have proven so difficult.	DISCUSS
44	46	H3	structure_element	Having all 16 VH:VL pairs with the same CDR H3 provides some insights into why molecular modeling efforts of CDR H3 have proven so difficult.	DISCUSS
109	112	CDR	structure_element	Having all 16 VH:VL pairs with the same CDR H3 provides some insights into why molecular modeling efforts of CDR H3 have proven so difficult.	DISCUSS
113	115	H3	structure_element	Having all 16 VH:VL pairs with the same CDR H3 provides some insights into why molecular modeling efforts of CDR H3 have proven so difficult.	DISCUSS
69	73	Fabs	structure_element	As mentioned in the Results section, this data set is composed of 21 Fabs, since 5 of the 16 variants have 2 Fab copies in the asymmetric unit.	DISCUSS
109	112	Fab	structure_element	As mentioned in the Results section, this data set is composed of 21 Fabs, since 5 of the 16 variants have 2 Fab copies in the asymmetric unit.	DISCUSS
11	15	Fabs	structure_element	For the 18 Fabs with complete backbone atoms for CDR H3, 10 have conformations similar to that of the parent, while the others have significantly different conformations (Fig. 6).	DISCUSS
49	52	CDR	structure_element	For the 18 Fabs with complete backbone atoms for CDR H3, 10 have conformations similar to that of the parent, while the others have significantly different conformations (Fig. 6).	DISCUSS
53	55	H3	structure_element	For the 18 Fabs with complete backbone atoms for CDR H3, 10 have conformations similar to that of the parent, while the others have significantly different conformations (Fig. 6).	DISCUSS
28	31	CDR	structure_element	Thus, it is likely that the CDR H3 conformation is dependent upon 2 dominating factors: 1) amino acid sequence; and 2) VH and VL context.	DISCUSS
32	34	H3	structure_element	Thus, it is likely that the CDR H3 conformation is dependent upon 2 dominating factors: 1) amino acid sequence; and 2) VH and VL context.	DISCUSS
119	121	VH	structure_element	Thus, it is likely that the CDR H3 conformation is dependent upon 2 dominating factors: 1) amino acid sequence; and 2) VH and VL context.	DISCUSS
126	128	VL	structure_element	Thus, it is likely that the CDR H3 conformation is dependent upon 2 dominating factors: 1) amino acid sequence; and 2) VH and VL context.	DISCUSS
103	108	VH:VL	complex_assembly	More than half of the variants retain the conformation of the parent despite having differences in the VH:VL pairing.	DISCUSS
23	33	structures	evidence	This subset includes 2 structures with 2 copies of the Fab in the asymmetric unit, all of which are nearly identical in conformation.	DISCUSS
55	58	Fab	structure_element	This subset includes 2 structures with 2 copies of the Fab in the asymmetric unit, all of which are nearly identical in conformation.	DISCUSS
16	26	structures	evidence	The remaining 8 structures exhibit “non-parental” conformations, indicating that the VH and VL context can also be a dominating factor influencing CDR H3.	DISCUSS
85	87	VH	structure_element	The remaining 8 structures exhibit “non-parental” conformations, indicating that the VH and VL context can also be a dominating factor influencing CDR H3.	DISCUSS
92	94	VL	structure_element	The remaining 8 structures exhibit “non-parental” conformations, indicating that the VH and VL context can also be a dominating factor influencing CDR H3.	DISCUSS
147	150	CDR	structure_element	The remaining 8 structures exhibit “non-parental” conformations, indicating that the VH and VL context can also be a dominating factor influencing CDR H3.	DISCUSS
151	153	H3	structure_element	The remaining 8 structures exhibit “non-parental” conformations, indicating that the VH and VL context can also be a dominating factor influencing CDR H3.	DISCUSS
23	33	structures	evidence	This subset also has 2 structures with 2 Fab copies in the asymmetric unit.	DISCUSS
41	44	Fab	structure_element	This subset also has 2 structures with 2 Fab copies in the asymmetric unit.	DISCUSS
65	77	stem regions	structure_element	Interestingly, as described earlier, these 2 pairs differ in the stem regions with the H1-69:L3-20 pair in the ‘extended’ conformation and H5-51:L4-1 pair in the ‘kinked’ conformation.	DISCUSS
87	98	H1-69:L3-20	complex_assembly	Interestingly, as described earlier, these 2 pairs differ in the stem regions with the H1-69:L3-20 pair in the ‘extended’ conformation and H5-51:L4-1 pair in the ‘kinked’ conformation.	DISCUSS
112	120	extended	protein_state	Interestingly, as described earlier, these 2 pairs differ in the stem regions with the H1-69:L3-20 pair in the ‘extended’ conformation and H5-51:L4-1 pair in the ‘kinked’ conformation.	DISCUSS
139	149	H5-51:L4-1	complex_assembly	Interestingly, as described earlier, these 2 pairs differ in the stem regions with the H1-69:L3-20 pair in the ‘extended’ conformation and H5-51:L4-1 pair in the ‘kinked’ conformation.	DISCUSS
163	169	kinked	protein_state	Interestingly, as described earlier, these 2 pairs differ in the stem regions with the H1-69:L3-20 pair in the ‘extended’ conformation and H5-51:L4-1 pair in the ‘kinked’ conformation.	DISCUSS
4	7	CDR	structure_element	The CDR H3 conformational analysis shows that, for each set of variants of one HC paired with the 4 different LCs, both “parental” and “non-parental” conformations are observed.	DISCUSS
8	10	H3	structure_element	The CDR H3 conformational analysis shows that, for each set of variants of one HC paired with the 4 different LCs, both “parental” and “non-parental” conformations are observed.	DISCUSS
11	34	conformational analysis	experimental_method	The CDR H3 conformational analysis shows that, for each set of variants of one HC paired with the 4 different LCs, both “parental” and “non-parental” conformations are observed.	DISCUSS
79	81	HC	structure_element	The CDR H3 conformational analysis shows that, for each set of variants of one HC paired with the 4 different LCs, both “parental” and “non-parental” conformations are observed.	DISCUSS
110	113	LCs	structure_element	The CDR H3 conformational analysis shows that, for each set of variants of one HC paired with the 4 different LCs, both “parental” and “non-parental” conformations are observed.	DISCUSS
74	76	LC	structure_element	The same variability is observed for the sets of variants composed of one LC paired with each of the 4 HCs.	DISCUSS
103	106	HCs	structure_element	The same variability is observed for the sets of variants composed of one LC paired with each of the 4 HCs.	DISCUSS
64	66	HC	structure_element	Thus, no patterns of conformational preference for a particular HC or LC emerge to shed any direct light on what drives the conformational differences.	DISCUSS
70	72	LC	structure_element	Thus, no patterns of conformational preference for a particular HC or LC emerge to shed any direct light on what drives the conformational differences.	DISCUSS
65	67	H3	structure_element	This finding supports the hypothesis of Weitzner et al. that the H3 conformation is controlled both by its sequence and its environment.	DISCUSS
49	59	tilt angle	evidence	In looking at a possible correlation between the tilt angle and the conformation of CDR H3, no clear trends are observed.	DISCUSS
84	87	CDR	structure_element	In looking at a possible correlation between the tilt angle and the conformation of CDR H3, no clear trends are observed.	DISCUSS
88	90	H3	structure_element	In looking at a possible correlation between the tilt angle and the conformation of CDR H3, no clear trends are observed.	DISCUSS
14	25	H1-69:L3-20	complex_assembly	Two variants, H1-69:L3-20 and H3-23:L3-20, have the largest differences in the tilt angles compared to other variants as seen in Table 3.	DISCUSS
30	41	H3-23:L3-20	complex_assembly	Two variants, H1-69:L3-20 and H3-23:L3-20, have the largest differences in the tilt angles compared to other variants as seen in Table 3.	DISCUSS
13	18	VH:VL	complex_assembly	The absolute VH:VL orientation parameters for the 2 Fabs (Table S2) show significant deviation in HL, LC1 and HC2 values (2-3 standard deviations from the mean).	DISCUSS
19	41	orientation parameters	evidence	The absolute VH:VL orientation parameters for the 2 Fabs (Table S2) show significant deviation in HL, LC1 and HC2 values (2-3 standard deviations from the mean).	DISCUSS
52	56	Fabs	structure_element	The absolute VH:VL orientation parameters for the 2 Fabs (Table S2) show significant deviation in HL, LC1 and HC2 values (2-3 standard deviations from the mean).	DISCUSS
85	94	deviation	evidence	The absolute VH:VL orientation parameters for the 2 Fabs (Table S2) show significant deviation in HL, LC1 and HC2 values (2-3 standard deviations from the mean).	DISCUSS
98	100	HL	structure_element	The absolute VH:VL orientation parameters for the 2 Fabs (Table S2) show significant deviation in HL, LC1 and HC2 values (2-3 standard deviations from the mean).	DISCUSS
102	105	LC1	structure_element	The absolute VH:VL orientation parameters for the 2 Fabs (Table S2) show significant deviation in HL, LC1 and HC2 values (2-3 standard deviations from the mean).	DISCUSS
110	113	HC2	structure_element	The absolute VH:VL orientation parameters for the 2 Fabs (Table S2) show significant deviation in HL, LC1 and HC2 values (2-3 standard deviations from the mean).	DISCUSS
21	32	H3-23:L3-20	complex_assembly	One of the variants, H3-23:L3-20, has the CDR H3 conformation similar to the parent, but the other, H1-69:L3-20, is different.	DISCUSS
42	45	CDR	structure_element	One of the variants, H3-23:L3-20, has the CDR H3 conformation similar to the parent, but the other, H1-69:L3-20, is different.	DISCUSS
46	48	H3	structure_element	One of the variants, H3-23:L3-20, has the CDR H3 conformation similar to the parent, but the other, H1-69:L3-20, is different.	DISCUSS
100	111	H1-69:L3-20	complex_assembly	One of the variants, H3-23:L3-20, has the CDR H3 conformation similar to the parent, but the other, H1-69:L3-20, is different.	DISCUSS
49	60	H1-69:L3-20	complex_assembly	As noted in the Results section, the 2 variants, H1-69:L3-20 and H3-23:L3-20, are outliers in terms of the tilt angle; at the same time, both have the smallest VH:VL interface.	DISCUSS
65	76	H3-23:L3-20	complex_assembly	As noted in the Results section, the 2 variants, H1-69:L3-20 and H3-23:L3-20, are outliers in terms of the tilt angle; at the same time, both have the smallest VH:VL interface.	DISCUSS
107	117	tilt angle	evidence	As noted in the Results section, the 2 variants, H1-69:L3-20 and H3-23:L3-20, are outliers in terms of the tilt angle; at the same time, both have the smallest VH:VL interface.	DISCUSS
160	175	VH:VL interface	site	As noted in the Results section, the 2 variants, H1-69:L3-20 and H3-23:L3-20, are outliers in terms of the tilt angle; at the same time, both have the smallest VH:VL interface.	DISCUSS
14	24	interfaces	site	These smaller interfaces may perhaps translate to a significant deviation in how VH is oriented relative to VL than the other variants.	DISCUSS
81	83	VH	structure_element	These smaller interfaces may perhaps translate to a significant deviation in how VH is oriented relative to VL than the other variants.	DISCUSS
108	110	VL	structure_element	These smaller interfaces may perhaps translate to a significant deviation in how VH is oriented relative to VL than the other variants.	DISCUSS
76	81	VH:VL	complex_assembly	These deviations from the other variants can also be seen to some extent in VH:VL orientation parameters in Table S2, as well as in the smaller number of residues involved in the VH:VL interfaces of these 2 variants (Fig. S5).	DISCUSS
179	195	VH:VL interfaces	site	These deviations from the other variants can also be seen to some extent in VH:VL orientation parameters in Table S2, as well as in the smaller number of residues involved in the VH:VL interfaces of these 2 variants (Fig. S5).	DISCUSS
64	68	CDRs	structure_element	These differences undoubtedly influence the conformation of the CDRs, in particular CDR H1 (Fig. 1A) and CDR L1 (Fig. 3C), especially with the tandem glycines and multiple serines present, respectively.	DISCUSS
84	87	CDR	structure_element	These differences undoubtedly influence the conformation of the CDRs, in particular CDR H1 (Fig. 1A) and CDR L1 (Fig. 3C), especially with the tandem glycines and multiple serines present, respectively.	DISCUSS
88	90	H1	structure_element	These differences undoubtedly influence the conformation of the CDRs, in particular CDR H1 (Fig. 1A) and CDR L1 (Fig. 3C), especially with the tandem glycines and multiple serines present, respectively.	DISCUSS
105	108	CDR	structure_element	These differences undoubtedly influence the conformation of the CDRs, in particular CDR H1 (Fig. 1A) and CDR L1 (Fig. 3C), especially with the tandem glycines and multiple serines present, respectively.	DISCUSS
109	111	L1	structure_element	These differences undoubtedly influence the conformation of the CDRs, in particular CDR H1 (Fig. 1A) and CDR L1 (Fig. 3C), especially with the tandem glycines and multiple serines present, respectively.	DISCUSS
150	158	glycines	residue_name	These differences undoubtedly influence the conformation of the CDRs, in particular CDR H1 (Fig. 1A) and CDR L1 (Fig. 3C), especially with the tandem glycines and multiple serines present, respectively.	DISCUSS
172	179	serines	residue_name	These differences undoubtedly influence the conformation of the CDRs, in particular CDR H1 (Fig. 1A) and CDR L1 (Fig. 3C), especially with the tandem glycines and multiple serines present, respectively.	DISCUSS
38	48	antibodies	protein_type	Pairing of different germlines yields antibodies with various degrees of stability.	DISCUSS
20	40	melting temperatures	evidence	As indicated by the melting temperatures, germlines H1-69 and H3-23 for HC and germline L1-39 for LC produce more stable Fabs compared to the other germlines in the experimental set.	DISCUSS
52	57	H1-69	mutant	As indicated by the melting temperatures, germlines H1-69 and H3-23 for HC and germline L1-39 for LC produce more stable Fabs compared to the other germlines in the experimental set.	DISCUSS
62	67	H3-23	mutant	As indicated by the melting temperatures, germlines H1-69 and H3-23 for HC and germline L1-39 for LC produce more stable Fabs compared to the other germlines in the experimental set.	DISCUSS
72	74	HC	structure_element	As indicated by the melting temperatures, germlines H1-69 and H3-23 for HC and germline L1-39 for LC produce more stable Fabs compared to the other germlines in the experimental set.	DISCUSS
88	93	L1-39	mutant	As indicated by the melting temperatures, germlines H1-69 and H3-23 for HC and germline L1-39 for LC produce more stable Fabs compared to the other germlines in the experimental set.	DISCUSS
98	100	LC	structure_element	As indicated by the melting temperatures, germlines H1-69 and H3-23 for HC and germline L1-39 for LC produce more stable Fabs compared to the other germlines in the experimental set.	DISCUSS
114	120	stable	protein_state	As indicated by the melting temperatures, germlines H1-69 and H3-23 for HC and germline L1-39 for LC produce more stable Fabs compared to the other germlines in the experimental set.	DISCUSS
121	125	Fabs	structure_element	As indicated by the melting temperatures, germlines H1-69 and H3-23 for HC and germline L1-39 for LC produce more stable Fabs compared to the other germlines in the experimental set.	DISCUSS
52	54	LC	structure_element	One possible explanation of the clear preference of LC germline L1-39 is that CDR L3 has smaller residues at positions 91 and 94, allowing for more room to accommodate CDR H3.	DISCUSS
64	69	L1-39	mutant	One possible explanation of the clear preference of LC germline L1-39 is that CDR L3 has smaller residues at positions 91 and 94, allowing for more room to accommodate CDR H3.	DISCUSS
78	81	CDR	structure_element	One possible explanation of the clear preference of LC germline L1-39 is that CDR L3 has smaller residues at positions 91 and 94, allowing for more room to accommodate CDR H3.	DISCUSS
82	84	L3	structure_element	One possible explanation of the clear preference of LC germline L1-39 is that CDR L3 has smaller residues at positions 91 and 94, allowing for more room to accommodate CDR H3.	DISCUSS
119	121	91	residue_number	One possible explanation of the clear preference of LC germline L1-39 is that CDR L3 has smaller residues at positions 91 and 94, allowing for more room to accommodate CDR H3.	DISCUSS
126	128	94	residue_number	One possible explanation of the clear preference of LC germline L1-39 is that CDR L3 has smaller residues at positions 91 and 94, allowing for more room to accommodate CDR H3.	DISCUSS
168	171	CDR	structure_element	One possible explanation of the clear preference of LC germline L1-39 is that CDR L3 has smaller residues at positions 91 and 94, allowing for more room to accommodate CDR H3.	DISCUSS
172	174	H3	structure_element	One possible explanation of the clear preference of LC germline L1-39 is that CDR L3 has smaller residues at positions 91 and 94, allowing for more room to accommodate CDR H3.	DISCUSS
37	40	Tyr	residue_name	Other germlines have bulky residues, Tyr, Arg and Trp, at these positions, whereas L1-39 has Ser and Thr.	DISCUSS
42	45	Arg	residue_name	Other germlines have bulky residues, Tyr, Arg and Trp, at these positions, whereas L1-39 has Ser and Thr.	DISCUSS
50	53	Trp	residue_name	Other germlines have bulky residues, Tyr, Arg and Trp, at these positions, whereas L1-39 has Ser and Thr.	DISCUSS
83	88	L1-39	mutant	Other germlines have bulky residues, Tyr, Arg and Trp, at these positions, whereas L1-39 has Ser and Thr.	DISCUSS
93	96	Ser	residue_name	Other germlines have bulky residues, Tyr, Arg and Trp, at these positions, whereas L1-39 has Ser and Thr.	DISCUSS
101	104	Thr	residue_name	Other germlines have bulky residues, Tyr, Arg and Trp, at these positions, whereas L1-39 has Ser and Thr.	DISCUSS
47	49	VL	structure_element	Various combinations of germline sequences for VL and VH impose certain constraints on CDR H3, which has to adapt to the environment.	DISCUSS
54	56	VH	structure_element	Various combinations of germline sequences for VL and VH impose certain constraints on CDR H3, which has to adapt to the environment.	DISCUSS
87	90	CDR	structure_element	Various combinations of germline sequences for VL and VH impose certain constraints on CDR H3, which has to adapt to the environment.	DISCUSS
91	93	H3	structure_element	Various combinations of germline sequences for VL and VH impose certain constraints on CDR H3, which has to adapt to the environment.	DISCUSS
7	14	compact	protein_state	A more compact CDR L3 may be beneficial in this situation.	DISCUSS
15	18	CDR	structure_element	A more compact CDR L3 may be beneficial in this situation.	DISCUSS
19	21	L3	structure_element	A more compact CDR L3 may be beneficial in this situation.	DISCUSS
43	45	LC	structure_element	At the other end of the stability range is LC germline L3-20, which yields antibodies with the lowest Tms.	DISCUSS
55	60	L3-20	mutant	At the other end of the stability range is LC germline L3-20, which yields antibodies with the lowest Tms.	DISCUSS
75	85	antibodies	protein_type	At the other end of the stability range is LC germline L3-20, which yields antibodies with the lowest Tms.	DISCUSS
102	105	Tms	evidence	At the other end of the stability range is LC germline L3-20, which yields antibodies with the lowest Tms.	DISCUSS
20	25	H3-53	mutant	While pairings with H3-53 and H5-51 may be safely called a mismatch, those with H1-69 and H3-23 have Tms about 5-6° higher.	DISCUSS
30	35	H5-51	mutant	While pairings with H3-53 and H5-51 may be safely called a mismatch, those with H1-69 and H3-23 have Tms about 5-6° higher.	DISCUSS
80	85	H1-69	mutant	While pairings with H3-53 and H5-51 may be safely called a mismatch, those with H1-69 and H3-23 have Tms about 5-6° higher.	DISCUSS
90	95	H3-23	mutant	While pairings with H3-53 and H5-51 may be safely called a mismatch, those with H1-69 and H3-23 have Tms about 5-6° higher.	DISCUSS
101	104	Tms	evidence	While pairings with H3-53 and H5-51 may be safely called a mismatch, those with H1-69 and H3-23 have Tms about 5-6° higher.	DISCUSS
17	21	Fabs	structure_element	Curiously, the 2 Fabs, H1-69:L3-20 and H3-23:L3-20, deviate markedly in their tilt angles from the rest of the panel.	DISCUSS
23	34	H1-69:L3-20	complex_assembly	Curiously, the 2 Fabs, H1-69:L3-20 and H3-23:L3-20, deviate markedly in their tilt angles from the rest of the panel.	DISCUSS
39	50	H3-23:L3-20	complex_assembly	Curiously, the 2 Fabs, H1-69:L3-20 and H3-23:L3-20, deviate markedly in their tilt angles from the rest of the panel.	DISCUSS
78	89	tilt angles	evidence	Curiously, the 2 Fabs, H1-69:L3-20 and H3-23:L3-20, deviate markedly in their tilt angles from the rest of the panel.	DISCUSS
40	51	tilt angles	evidence	It is possible that by adopting extreme tilt angles the structure modulates CDR H3 and its environment, which apparently cannot be achieved solely by conformational rearrangement of the CDR.	DISCUSS
56	65	structure	evidence	It is possible that by adopting extreme tilt angles the structure modulates CDR H3 and its environment, which apparently cannot be achieved solely by conformational rearrangement of the CDR.	DISCUSS
76	79	CDR	structure_element	It is possible that by adopting extreme tilt angles the structure modulates CDR H3 and its environment, which apparently cannot be achieved solely by conformational rearrangement of the CDR.	DISCUSS
80	82	H3	structure_element	It is possible that by adopting extreme tilt angles the structure modulates CDR H3 and its environment, which apparently cannot be achieved solely by conformational rearrangement of the CDR.	DISCUSS
186	189	CDR	structure_element	It is possible that by adopting extreme tilt angles the structure modulates CDR H3 and its environment, which apparently cannot be achieved solely by conformational rearrangement of the CDR.	DISCUSS
22	37	VH:VL interface	site	Note that most of the VH:VL interface residues are invariant; therefore, significant change of the tilt angle must come with a penalty in free energy.	DISCUSS
15	25	antibodies	protein_type	Yet, for the 2 antibodies, the total gain in stability merits the domain repacking.	DISCUSS
30	33	Fab	structure_element	Overall, the stability of the Fab, as measured by Tm, is a result of the mutual adjustment of the HC and LC variable domains and adjustment of CDR H3 to the VH:VL cleft.	DISCUSS
50	52	Tm	evidence	Overall, the stability of the Fab, as measured by Tm, is a result of the mutual adjustment of the HC and LC variable domains and adjustment of CDR H3 to the VH:VL cleft.	DISCUSS
98	100	HC	structure_element	Overall, the stability of the Fab, as measured by Tm, is a result of the mutual adjustment of the HC and LC variable domains and adjustment of CDR H3 to the VH:VL cleft.	DISCUSS
105	107	LC	structure_element	Overall, the stability of the Fab, as measured by Tm, is a result of the mutual adjustment of the HC and LC variable domains and adjustment of CDR H3 to the VH:VL cleft.	DISCUSS
108	124	variable domains	structure_element	Overall, the stability of the Fab, as measured by Tm, is a result of the mutual adjustment of the HC and LC variable domains and adjustment of CDR H3 to the VH:VL cleft.	DISCUSS
143	146	CDR	structure_element	Overall, the stability of the Fab, as measured by Tm, is a result of the mutual adjustment of the HC and LC variable domains and adjustment of CDR H3 to the VH:VL cleft.	DISCUSS
147	149	H3	structure_element	Overall, the stability of the Fab, as measured by Tm, is a result of the mutual adjustment of the HC and LC variable domains and adjustment of CDR H3 to the VH:VL cleft.	DISCUSS
157	168	VH:VL cleft	site	Overall, the stability of the Fab, as measured by Tm, is a result of the mutual adjustment of the HC and LC variable domains and adjustment of CDR H3 to the VH:VL cleft.	DISCUSS
167	176	structure	evidence	The final conformation represents an energetic minimum; however, in most cases it is very shallow, so that a single mutation can cause a dramatic rearrangement of the structure.	DISCUSS
33	51	structural library	experimental_method	In summary, the analysis of this structural library of germline variants composed of all pairs of 4 HCs and 4LCs, all with the same CDR H3, offers some unique insights into antibody structure and how pairing and sequence may influence, or not, the canonical structures of the L1, L2, L3, H1 and H2 CDRs.	DISCUSS
100	103	HCs	structure_element	In summary, the analysis of this structural library of germline variants composed of all pairs of 4 HCs and 4LCs, all with the same CDR H3, offers some unique insights into antibody structure and how pairing and sequence may influence, or not, the canonical structures of the L1, L2, L3, H1 and H2 CDRs.	DISCUSS
109	112	LCs	structure_element	In summary, the analysis of this structural library of germline variants composed of all pairs of 4 HCs and 4LCs, all with the same CDR H3, offers some unique insights into antibody structure and how pairing and sequence may influence, or not, the canonical structures of the L1, L2, L3, H1 and H2 CDRs.	DISCUSS
132	135	CDR	structure_element	In summary, the analysis of this structural library of germline variants composed of all pairs of 4 HCs and 4LCs, all with the same CDR H3, offers some unique insights into antibody structure and how pairing and sequence may influence, or not, the canonical structures of the L1, L2, L3, H1 and H2 CDRs.	DISCUSS
136	138	H3	structure_element	In summary, the analysis of this structural library of germline variants composed of all pairs of 4 HCs and 4LCs, all with the same CDR H3, offers some unique insights into antibody structure and how pairing and sequence may influence, or not, the canonical structures of the L1, L2, L3, H1 and H2 CDRs.	DISCUSS
173	181	antibody	protein_type	In summary, the analysis of this structural library of germline variants composed of all pairs of 4 HCs and 4LCs, all with the same CDR H3, offers some unique insights into antibody structure and how pairing and sequence may influence, or not, the canonical structures of the L1, L2, L3, H1 and H2 CDRs.	DISCUSS
182	191	structure	evidence	In summary, the analysis of this structural library of germline variants composed of all pairs of 4 HCs and 4LCs, all with the same CDR H3, offers some unique insights into antibody structure and how pairing and sequence may influence, or not, the canonical structures of the L1, L2, L3, H1 and H2 CDRs.	DISCUSS
276	278	L1	structure_element	In summary, the analysis of this structural library of germline variants composed of all pairs of 4 HCs and 4LCs, all with the same CDR H3, offers some unique insights into antibody structure and how pairing and sequence may influence, or not, the canonical structures of the L1, L2, L3, H1 and H2 CDRs.	DISCUSS
280	282	L2	structure_element	In summary, the analysis of this structural library of germline variants composed of all pairs of 4 HCs and 4LCs, all with the same CDR H3, offers some unique insights into antibody structure and how pairing and sequence may influence, or not, the canonical structures of the L1, L2, L3, H1 and H2 CDRs.	DISCUSS
284	286	L3	structure_element	In summary, the analysis of this structural library of germline variants composed of all pairs of 4 HCs and 4LCs, all with the same CDR H3, offers some unique insights into antibody structure and how pairing and sequence may influence, or not, the canonical structures of the L1, L2, L3, H1 and H2 CDRs.	DISCUSS
288	290	H1	structure_element	In summary, the analysis of this structural library of germline variants composed of all pairs of 4 HCs and 4LCs, all with the same CDR H3, offers some unique insights into antibody structure and how pairing and sequence may influence, or not, the canonical structures of the L1, L2, L3, H1 and H2 CDRs.	DISCUSS
295	297	H2	structure_element	In summary, the analysis of this structural library of germline variants composed of all pairs of 4 HCs and 4LCs, all with the same CDR H3, offers some unique insights into antibody structure and how pairing and sequence may influence, or not, the canonical structures of the L1, L2, L3, H1 and H2 CDRs.	DISCUSS
298	302	CDRs	structure_element	In summary, the analysis of this structural library of germline variants composed of all pairs of 4 HCs and 4LCs, all with the same CDR H3, offers some unique insights into antibody structure and how pairing and sequence may influence, or not, the canonical structures of the L1, L2, L3, H1 and H2 CDRs.	DISCUSS
18	21	CDR	structure_element	Comparison of the CDR H3s reveals a large set of variants with conformations similar to the parent, while a second set has significant conformational variability, indicating that both the sequence and the structural context define the CDR H3 conformation.	DISCUSS
22	25	H3s	structure_element	Comparison of the CDR H3s reveals a large set of variants with conformations similar to the parent, while a second set has significant conformational variability, indicating that both the sequence and the structural context define the CDR H3 conformation.	DISCUSS
235	238	CDR	structure_element	Comparison of the CDR H3s reveals a large set of variants with conformations similar to the parent, while a second set has significant conformational variability, indicating that both the sequence and the structural context define the CDR H3 conformation.	DISCUSS
239	241	H3	structure_element	Comparison of the CDR H3s reveals a large set of variants with conformations similar to the parent, while a second set has significant conformational variability, indicating that both the sequence and the structural context define the CDR H3 conformation.	DISCUSS
39	50	H1-69:L3-20	complex_assembly	Quite unexpectedly, 2 of the variants, H1-69:L3-20 and H3-53:L4-1, have the ‘extended’ stem region differing from the other 14 that have a ‘kinked’ stem region.	DISCUSS
55	65	H3-53:L4-1	complex_assembly	Quite unexpectedly, 2 of the variants, H1-69:L3-20 and H3-53:L4-1, have the ‘extended’ stem region differing from the other 14 that have a ‘kinked’ stem region.	DISCUSS
77	85	extended	protein_state	Quite unexpectedly, 2 of the variants, H1-69:L3-20 and H3-53:L4-1, have the ‘extended’ stem region differing from the other 14 that have a ‘kinked’ stem region.	DISCUSS
87	98	stem region	structure_element	Quite unexpectedly, 2 of the variants, H1-69:L3-20 and H3-53:L4-1, have the ‘extended’ stem region differing from the other 14 that have a ‘kinked’ stem region.	DISCUSS
140	146	kinked	protein_state	Quite unexpectedly, 2 of the variants, H1-69:L3-20 and H3-53:L4-1, have the ‘extended’ stem region differing from the other 14 that have a ‘kinked’ stem region.	DISCUSS
148	159	stem region	structure_element	Quite unexpectedly, 2 of the variants, H1-69:L3-20 and H3-53:L4-1, have the ‘extended’ stem region differing from the other 14 that have a ‘kinked’ stem region.	DISCUSS
45	48	CDR	structure_element	These data reveal the difficulty of modeling CDR H3 accurately, as shown again in Antibody Modeling Assessment II.	DISCUSS
49	51	H3	structure_element	These data reveal the difficulty of modeling CDR H3 accurately, as shown again in Antibody Modeling Assessment II.	DISCUSS
13	21	antibody	protein_type	Furthermore, antibody CDRs, H3 in particular, may go through conformational changes upon binding their targets, making structural prediction for docking purposes an even more difficult task.	DISCUSS
22	26	CDRs	structure_element	Furthermore, antibody CDRs, H3 in particular, may go through conformational changes upon binding their targets, making structural prediction for docking purposes an even more difficult task.	DISCUSS
28	30	H3	structure_element	Furthermore, antibody CDRs, H3 in particular, may go through conformational changes upon binding their targets, making structural prediction for docking purposes an even more difficult task.	DISCUSS
38	46	antibody	protein_type	Fortunately, for most applications of antibody modeling, such as engineering affinity and biophysical properties, an accurate CDR H3 structure is not always necessary.	DISCUSS
126	129	CDR	structure_element	Fortunately, for most applications of antibody modeling, such as engineering affinity and biophysical properties, an accurate CDR H3 structure is not always necessary.	DISCUSS
130	132	H3	structure_element	Fortunately, for most applications of antibody modeling, such as engineering affinity and biophysical properties, an accurate CDR H3 structure is not always necessary.	DISCUSS
133	142	structure	evidence	Fortunately, for most applications of antibody modeling, such as engineering affinity and biophysical properties, an accurate CDR H3 structure is not always necessary.	DISCUSS
38	41	CDR	structure_element	For those applications where accurate CDR structures are essential, such as docking, the results in this work demonstrate the importance of experimental structures.	DISCUSS
42	52	structures	evidence	For those applications where accurate CDR structures are essential, such as docking, the results in this work demonstrate the importance of experimental structures.	DISCUSS
153	163	structures	evidence	For those applications where accurate CDR structures are essential, such as docking, the results in this work demonstrate the importance of experimental structures.	DISCUSS
28	66	expression and crystallization methods	experimental_method	With the recent advances in expression and crystallization methods, Fab structures can be obtained rapidly.	DISCUSS
68	71	Fab	structure_element	With the recent advances in expression and crystallization methods, Fab structures can be obtained rapidly.	DISCUSS
72	82	structures	evidence	With the recent advances in expression and crystallization methods, Fab structures can be obtained rapidly.	DISCUSS
23	26	Fab	structure_element	The set of 16 germline Fab structures offers a unique dataset to facilitate software development for antibody modeling.	DISCUSS
27	37	structures	evidence	The set of 16 germline Fab structures offers a unique dataset to facilitate software development for antibody modeling.	DISCUSS
101	109	antibody	protein_type	The set of 16 germline Fab structures offers a unique dataset to facilitate software development for antibody modeling.	DISCUSS
65	75	structures	evidence	The results essentially support the underlying idea of canonical structures, indicating that most CDRs with germline sequences tend to adopt predefined conformations.	DISCUSS
98	102	CDRs	structure_element	The results essentially support the underlying idea of canonical structures, indicating that most CDRs with germline sequences tend to adopt predefined conformations.	DISCUSS
66	74	antibody	protein_type	From this point of view, a novel approach to design combinatorial antibody libraries would be to cover the range of CDR conformations that may not necessarily coincide with the germline usage in the human repertoire.	DISCUSS
116	119	CDR	structure_element	From this point of view, a novel approach to design combinatorial antibody libraries would be to cover the range of CDR conformations that may not necessarily coincide with the germline usage in the human repertoire.	DISCUSS
199	204	human	species	From this point of view, a novel approach to design combinatorial antibody libraries would be to cover the range of CDR conformations that may not necessarily coincide with the germline usage in the human repertoire.	DISCUSS
80	90	antibodies	protein_type	This would insure more structural diversity, leading to a more diverse panel of antibodies that would bind to a broad spectrum of targets.	DISCUSS