Patent Abstract:
The invention relates to the three-dimensional structure of a crystal of an EphB4 receptor complexed with a ligand. The three-dimensional structure of a Receptor-Ligand Complex is disclosed. The receptor-ligand crystal structure, wherein the ligand is an inhibitor molecule, is useful for providing structural information that may be integrated into drug screening and drug design processes. Thus, the invention also relates to methods for utilizing the crystal structure of the Receptor-Ligand Complex for identifying, designing, selecting, or testing inhibitors of the EphB4 receptor protein, such inhibitors being useful as therapeutics for the treatment or modulation of i) diseases; ii) disease symptoms; or iii) the effect of other physiological events mediated by the receptor.

Full Description:
CROSS-REFERENCE TO RELATED APPLICATIONS  
       [0001]     This application claims priority from U.S. Provisional Application Ser. No. 60/832,375 filed on Jul. 21, 2006, which is incorporated herein by reference in its entirety. 
     
    
     STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT  
       [0002]     Not Applicable.  
       INCORPORATION-BY-REFERENCE OF MATERIAL SUBMITTED ON A COMPACT DISC  
       [0003]     The Sequence Listing, which is a part of the present disclosure, includes a computer file “10000-0027_ST25.txt” generated by U.S. Patent &amp; Trademark Office Patent In Version 3.4 software comprising nucleotide and/or amino acid sequences of the present invention. The subject matter of the Sequence Listing is incorporated herein by reference in its entirety.  
       FIELD  
       [0004]     The present invention relates to a three-dimensional structure of a receptor tyrosine kinase from the erythropoietin-producing hepatocellular carcinoma family of receptor tyrosine kinases (“Eph”), particularly EphB4 or similar polypeptide complexed with an ephrinB2 or ephrinB2 analog (“Receptor-Ligand Complex”), three-dimensional coordinates of a Receptor-Ligand Complex, models thereof, and uses of such structures and models.  
       INTRODUCTION  
       [0005]     The Eph receptor tyrosine kinases and their ligands, the ephrins, regulate numerous biological processes in developing and adult tissues and have been implicated in cancer progression and in pathological forms of angiogenesis. For example, the Eph receptors and their ligands, the ephrins, play critical roles in angiogenesis during embryonic development as well as in adult tissues (Brantley-Sieders and Chen, 2004; Cheng et al., 2002; Gale and Yancopoulos, 1999; Kullander and Klein, 2002). The Eph family of receptor tyrosine kinases also regulates many other biological processes, including tissue patterning, axonal guidance, and as more recently discovered, tumorigenesis (Carmeliet and Collen, 1999; Ferrara, 1999; Pasquale, 2005; Wilkinson, 2000). Both the Eph receptor and the ephrin ligand are membrane bound, and therefore require cell-cell contact to signal a cellular response. The interaction between Eph receptors and ephrins on adjacent cell surfaces results in multimerization and clustering of the Eph-ephrin complexes, leading to forward signaling in the Eph-expressing cell and reverse signaling in the ephrin-expressing cell. EphB4 belongs to the Eph (erythropoietin-producing hepatocellular carcinoma) family of receptor tyrosine kinases, which is divided into two subclasses, A and B. based on binding preferences and sequence conservation (Gale et al., 1996). In general, EphA receptors (EphA1-EphA10) bind to glycosyl phosphatidyl inositol-(GPI) anchored ephrin-A ligands (ephrin-A1-ephrin-A6), while EphB receptors (EphB1-EphB6) interact with transmembrane ephrin-B ligands (ephrin-B1-ephrin-B3) (Eph Nomenclature Committee, 1997). While interactions between the Eph receptors and ephrin ligands of the same subclass are quite promiscuous, interactions between subclasses are rare. A few cross-subclass exceptions include the EphA4-ephrin-B2/B3 interactions (Takemoto et al., 2002), and the EphB2-ephrinA5 interaction, which has been characterized structurally (Himanen et al., 2004). EphB4 is unique within the Eph family in that it selectively binds ephrin-B2, while demonstrating only weak binding for both ephrin-B1 and ephrin-B3.  
         [0006]     Eph receptors have a modular structure, consisting of an N-terminal ephrin binding domain adjacent to a cysteine-rich domain and two fibronectin type III repeats in the extracellular region. The intracellular region consists of a juxtamembrane domain, a conserved tyrosine kinase domain, a C-terminal sterile α-domain (SAM), and a PDZ binding motif. The N-terminal 180 amino acid globular domain is sufficient for high-affinity ligand binding (Himanen et al., 2001).  
         [0007]     The EphB4-ephrinB2 interaction is important in angiogenesis and given that EphB4 is overexpressed in several tumor types (Dodelet, V. C., and Pasquale, E. B. (2000)  Oncogene  19, 5614-5619; Nakamoto, M., and Bergemann, A. D. (2002)  Microsc Res Tech  59, 58-67; Liu, W., Ahmad, S. A., Jung, Y. D., Reinmuth, N., Fan, F., Bucana, C. D., and Ellis, L. M. (2002)  Cancer  94, 934-939; Berclaz, G., Karamitopoulou, E., Mazzucchelli, L., Rohrbach, V., Dreher, E., Ziemiecki, A., and Andres, A. C. (2003)  Ann Oncol  14, 220-226), modulating this protein-protein interaction is a potential approach to slowing tumor angiogenesis and tumor growth. In mouse models of breast cancer, high EphB4 expression correlates with increased malignancy and tumor aggressiveness (Andres, A. C., Reid, H. H., Zurcher, G., Blaschke, R. J., Albrecht, D., and Ziemiecki, A. (1994)  Oncogene  9, 1461-1467; Nikolova, Z., Djonov, V., Zuercher, G., Andres, A. C., and Ziemiecki, A. (1998)  J Cell Sci  111 (Pt 18), 2741-2751; Munarini, N., Jager, R., Abderhalden, S., Zuercher, G., Rohrbach, V., Loercher, S., Pfanner-Meyer, B., Andres, A. C., and Ziemiecki, A. (2002)  J Cell Sci  115, 25-37). EphB4 expression is also increased in human primary infiltrating ductal breast carcinoma and is correlated to increased malignancy (Berclaz, G., Andres, A. C., Albrecht, D., Dreher, E., Ziemiecki, A., Gusterson, B. A., and Crompton, M. R. (1996)  Biochem Biophys Res Commun  226, 869-875). There is evidence that the EphB4 ectodomain stimulates endothelial cell migration and proliferation, suggesting that ephrinB2-expressing endothelial cells interact with the EphB4 ectodomain to promote angiogenesis and tumor progression. Furthermore, a kinase-deficient EphB4 mutant has been shown to increase breast cancer cell growth indicating that downstream forward kinase signaling is not an absolute requirement for tumorigenesis, at least in breast cancer cells (Noren, N. K., Lu, M., Freeman, A. L., Koolpe, M., and Pasquale, E. B. (2004)  Proc Natl Acad Sci USA  101, 5583-5588). Several groups have more recently demonstrated that the full extracellular domain of EphB4 is indeed a viable therapeutic target First, the soluble extracellular domain of EphB4 was described to block both forward and reverse signaling, resulting in an inhibition of tumor growth in vivo (Kertesz, N., Krasnoperov, V., Reddy, R., Leshanski, L., Kumar, S. R., Zozulya, S., and Gill, P. S. (2006) Blood 107, 2330-2338; Martiny-Baron, G., Korff, T., Schaffner, F., Esser, N., Eggstein, S., Marme, D., and Augustin, H. G. (2004)  Neoplasia  6, 248-257).  
         [0008]     Second, phage display studies have identified a peptide (TNYL-RAW) which antagonizes the EphB4-ephrinB2 interaction in the high nanomolar range (Koolpe, M., Burgess, R., Dail, M., and Pasquale, E. B. (2005)  J Biol Chem  280, 17301-17311). The crystal structure of the EphB4 receptor in complex with the phage-derived TNYL-RAW peptide (SEQ ID NO: 1) revealed that the peptide binds to the ephrin binding cavity of the receptor, effectively inhibiting interaction with the ligand (Chrencik, J. E., Brooun, A., Recht, M. I., Kraus, M. L., Koolpe, M., Kolatkar, A. R., Bruce, R. H., Martiny-Baron, G., Widmer, H., Pasquale, E. B., and Kuhn, P. (2006)  Structure  14, 321-330). However, a more complete understanding of the biological role of EphB4-ephrinB2 signaling in tumorigenesis and in forms of pathological angiogenesis is now required.  
         [0009]     Despite attempts to model the structural changes of EphB4 upon ligand binding, a detailed view of conformational arrangements of an EphB4 receptor in complex with ephrinB2 has remained elusive. Thus, the development of useful reagents for treatment or diagnosis of disease was hindered by lack of structural information of such a Receptor-Ligand Complex. Therefore, there is a need in the art to elucidate the three-dimensional structure and models of Receptor-Ligand Complexes, and to use such structures and models in therapeutic strategies, such as drug design. 
     
    
     DRAWINGS  
       [0010]     Those of skill in the art will understand that the drawings, described below, are for illustrative purposes only. The drawings are not intended to limit the scope of the present teachings in any way.  
         [0011]      FIG. 1 . The ephrin binding domain of the EphB4 receptor in complex with the ephrinB2 extracellular domain. The EphB4 receptor (right) consists of a jellyroll folding topology with 13 anti-parallel B-sheets connected by loops of varying lengths, whereas the ephrin ligand (left) is similar to the Greek key folding topology. The interface is formed by insertion of the ligand G-H loop into the hydrophobic binding cleft of EphB4.  
         [0012]      FIG. 2 . Stereoview of the superposition of the Eph receptor ligand binding domains from the EphB4.ephrinB2 (thick grey line), EphB2.ephrinB2 (thin grey line), and EphB4.TNYL-RAW complex structures (thick line with spheres). Clear deviation is seen at the J-K loop, whereas more minor changes are seen in the receptor D-E and G-H loops (Protein Data Bank code 1 KGY). The overall root mean square deviation between the EphB4.ephrinB2 and the EphB2.ephrinB2 and EphB4-TNYL-RAW structures is 5.0 and 2.5 Å, respectively.  FIG. 3 . Stereoview of σA weighted 2 F obs -F calc  electron density at 2.0 Å resolution, contoured at 1σ for the EphB4.ephrinB2 interface. The ephrinB2 is the leftmost molecule (labeled) and the EphB4 is at the right (labeled). Clear density of the interface shows Phe-120 in a novel position with respect to previously described structures in order to interact with Leu-95.  
         [0013]      FIG. 4 . Detailed ligplot diagram of critical EphB4.ephrinB2 interactions. All interactions are less than 4 Å and are indicated by dashed lines. The ligand is depicted with all bonds shown, whereas receptor residues are drawn schematically.  
         [0014]      FIG. 5 . EphrinB2 specificity region in the EphB2/EphB4.ephrinB2 complexes. Left, the region near the EphB4 Leu-95R of the EphB4.ephrinB2 complex structure is shown in schematic representation. The van der Waals interaction between the ephrinB2 Phe-120L and the EphB4 Leu-95R is depicted as a dotted line. Right, the region near the EphB2 Arg-103R of the EphB2.ephrinB2 complex structure is shown in the same orientation as that on the left. The EphB2 Arg-103R, Ser-156R, and Ser-107R side chains are shown as grey sticks. Hydrogen bonds between Arg-103R and the two serines are shown as dotted lines. The J-K loops of EphB2 and EphB4 are labeled highlighting the change in loop position between the two complexes.  
         [0015]      FIG. 6 . This figure illustrates binding of fluorescent peptide to wild type EphB4, EphB4 K149Q (A) and EphB4 L95R mutants. Increasing amount of EphB4 protein was added to wells containing 75 nM of fluorescent TNYL-RAW peptide. Fluorescent polarization was measured at room temperature after 30 min of incubation. Based on the structure of EphB4-ephrin-B2 complex, the substitution of L95 was predicted to impair EphB4 binding to ephrin-B2.  
         [0016]      FIG. 7 . This figure illustrates determination of K i  for TNYL-RAW. K i  were determined for both wild-type EphB4 (filled triangles) and EphB4 (K149Q) mutant (filled squares).  
         [0017]      FIG. 8 . This figure illustrates binding of fluorescent TNYL-RAW peptide in the presence of increasing concentration of DMSO. Increasing amounts of EphB4 protein were added to wells containing 75 nM of TNYL-RAW-Alexa-532 peptide. Fluorescent polarization was measured at room temperature.  
         [0018]      FIG. 9 . This figure illustrates Z-factor determination for EphB4-Alexa-532-TNYL-RAW fluorescent polarization assay. 
     
    
     DETAILED DESCRIPTION  
       [0019]     The present invention relates to the discovery of the three-dimensional structure of a Receptor-Ligand Complex, models of such three-dimensional structures, a method of structure-based drug design using such structures, the compounds identified by such methods and the use of such compounds in therapeutic compositions. In particular, the present invention involves the crystal structure of the EphB4 receptor in complex with ephrinB2 at a resolution of 2.0 Å. EphrinB2 is situated in a hydrophobic cleft of EphB4 corresponding to the cleft in EphB2 occupied by the ephrinB2 G-H loop. The crystal reveals critical structural features of EphB4 that, when in complex ephrinB2, provides a basis for antagonist design and modeling.  
         [0020]     In particular, the structural and thermodynamic characterization of the EphB4 receptor in complex with ephrinB2 is described. The structure reveals that the flexible J-K loop of EphB4 shifts significantly as compared to previous crystal structures, providing a new network of contacts to secure the interaction. In addition, using biophysical analysis, one amino acid, Leu-95, is identified which lines the ligand binding cavity of the EphB4 receptor and provides the molecular determinants for the unique specificity exhibited by the EphB4 receptor for the ephrinB2 ligand.  
         [0021]     A multiple sequence alignment with members of the EphB subclass reveals that the EphB4 receptor lacks a conserved arginine and instead contains a leucine at position 95. A Leu-95-Arg mutation was previously predicted to result in steric interference with the antagonistic TNYL-RAW peptide ligand (Chrencik et al.,  Structure,  2006, incorporated herein by reference in its entirety; SEQ ID NO: 1). This mutation also results in steric interference with Phe-120 in the G-H loop of ephrinB2 due to the different positioning of the J-K loop of EphB4. A leucine instead of an arginine at position 95 of the EphB4 receptor is sufficient to cause substantial structural rearrangement of the receptor J-K loop. Also provided is a novel position of the conserved Phe-120 in the high affinity FSPN sequence of the ephrinB2 G-H loop, suggesting that although ephrinB2 is conserved in structure in both receptor-bound and apo structures, there is variability within the rigid G-H loop to conform to a specific receptor.  
         [0022]     EphB4 binds only weakly to both ephrinB1 and ephrinB3, while exhibiting high affinity for ephrinB2. Considering the B-subclass ephrin G-H loop (ephrinB1-B3), it is interesting to speculate on why EphB4 preferentially binds ephrinB2 over other B-subclass ligands. EphrinB1 shares significant sequence identity with the high affinity ephrinB2 G-H loop, except at position 124, which is a Tyr in ephrinB1 and a Leu in ephrinB2. While Leu-124 forms no integral interactions with EphB4, the small size of the leucine allows tight packing within the receptor binding cavity. A leucine also maintains the hydrophobic nature of the binding cleft. Superposition of a tyrosine on the ephrinB2 structure would require the rearrangement of the EphB4 J-K loop in order to accommodate the bulky tyrosine, and, without being bound by a particular theory, this likely accounts for the reduced affinity of EphB4 for ephrinB1. The ephrinB3 G-H loop is also very similar to the ephrinB2 G-H loop but deviates in the FSPN sequence, which contains a tyrosine instead of the phenylalanine (YSPN). Phe-120 forms critical interactions with residues lining the EphB receptor-ephrinB2 binding cavity in the three complex crystal structures thus far described. In the previous crystal structures, Phe-120 extends to the surface of the binding cavity, adjacent to the receptor G-H loop. Superposition of a tyrosine on the EphB2-ephrinB2 structure would not affect the dynamics of the ligand binding cavity, and this residue is predicted to interact with several water molecules on the surface of the complex. However, in the present crystal structure, the Phe-120 of ephrinB2 is observed in a novel position, buried within the hydrophic binding cleft and forming interactions with Leu-95R and the Cys-61-Cys-184 disulfide bridge. Insertion of a tyrosine at this position would therefore result in both steric interference within the receptor binding cavity and a polar redistribution of the active site.  
         [0023]     Thermodynamic discrepancies between Eph receptor and ephrin binding can be considered in the design of therapeutics to treat disease related to the Eph receptor family. Iterative rounds of structure based drug design provide an understanding of the enthalpic and entropic contributions of small molecule compounds. In the case of the ephrin ligand, the G-H loop is predicted to reduce conformational entropy losses due to its rigidity, maximizing the effects of solvation entropy due to the hydrophobic nature of the Eph ligand binding cavity. The ephrin, on the other hand, can experience large losses in conformational entropy upon receptor binding which are compensated by favorable enthalpic gains between receptor and ephrin residues. The ephrin ligand, with entropically-driven binding, can interact with multiple members of the EphB family. In contrast, the TNYL-RAW peptide, with enthalpically-driven binding, is a specific inhibitor of the EphB4-ephrinB2 interaction.  
         [0024]     Accordingly, one aspect of the present invention includes a model of a Receptor-Ligand Complex in which the model represents a three-dimensional structure of a Receptor-Ligand Complex. Another aspect of the present invention includes the three-dimensional structure of a Receptor-Ligand Complex. A three-dimensional structure of a Receptor-Ligand Complex substantially conforms with the atomic coordinates represented in Table 1. According to the present invention, the use of the term “substantially conforms” refers to at least a portion of a three-dimensional structure of a Receptor-Ligand Complex which is sufficiently spatially similar to at least a portion of a specified three-dimensional configuration of a particular set of atomic coordinates (e.g., those represented by Table 1) to allow the three-dimensional structure of a Receptor-Ligand Complex to be modeled or calculated using the particular set of atomic coordinates as a basis for determining the atomic coordinates defining the three-dimensional configuration of a Receptor-Ligand Complex.  
         [0025]     More particularly, a structure that substantially conforms to a given set of atomic coordinates is a structure wherein at least about 50% of such structure has an average root-mean-square deviation (RMSD) of less than about 2.0 Å for the backbone atoms in secondary structure elements in each domain, and in various aspects, less than about 1.25 Å for the backbone atoms in secondary structure elements in each domain, and, in various aspects less than about 1.0 Å, in other aspects less than about 0.75 Å, less than about 0.5 Å, and, less than about 0.25 Å for the backbone atoms in secondary structure elements in each domain. In one aspect of the present invention, a structure that substantially conforms to a given set of atomic coordinates is a structure wherein at least about 75% of such structure has the recited average RMSD value, and in some aspects, at least about 90% of such structure has the recited average RMSD value, and in some aspects, about 100% of such structure has the recited average RMSD value. In particular, the above definition of “substantially conforms” can be extended to include atoms of amino acid side chains. As used herein, the phrase “common amino acid side chains” refers to amino acid side chains that are common to both the structure which substantially conforms to a given set of atomic coordinates and the structure that is actually represented by such atomic coordinates.  
         [0026]     In another aspect of the present invention, a three-dimensional structure that substantially conforms to a given set of atomic coordinates is a structure wherein at least about 50% of the common amino acid side chains have an average RMSD of less than about 2.0 Å, and in various aspects, less than about 1.25 Å, and, in other aspects, less than about 1.0 Å, less than about 0.75 Å, less than about 0.5 Å, and less than about 0.25 Å. In one aspect of the present invention, a structure that substantially conforms to a given set of atomic coordinates is a structure wherein at least about 75% of the common amino acid side chains have the recited average RMSD value, and in some aspects, at least about 90% of the common amino acid side chains have the recited average RMSD value, and in some aspects, about 100% of the common amino acid side chains have the recited average RMSD value.  
         [0027]     A three-dimensional structure of a Receptor-Ligand Complex which substantially conforms to a specified set of atomic coordinates can be modeled by a suitable modeling computer program such as MODELER (A. Sali and T. L. Blundell, J. Mol. Biol., vol. 234:779-815, 1993 as implemented in the Insight II software package Insight II, available from Accelerys (San Diego, Calif.)) and those software packages listed in the Examples, using information, for example, derived from the following data: (1) the amino acid sequence of the Receptor-Ligand Complex; (2) the amino acid sequence of the related portion(s) of the protein represented by the specified set of atomic coordinates having a three-dimensional configuration; and, (3) the atomic coordinates of the specified three-dimensional configuration. A three-dimensional structure of a Receptor-Ligand Complex which substantially conforms to a specified set of atomic coordinates can also be calculated by a method such as molecular replacement, which is described in detail below.  
         [0028]     A suitable three-dimensional structure of the Receptor-Ligand Complex for use in modeling or calculating the three-dimensional structure of another Receptor-Ligand Complex comprises the set of atomic coordinates represented in Table 1. The set of three-dimensional coordinates set forth in Table 1 is represented in standard Protein Data Bank format. The atomic coordinates have been deposited in the Protein Data Bank, having Accession No. 2HLE. According to the present invention, a Receptor-Ligand Complex has a three-dimensional structure which substantially conforms to the set of atomic coordinates represented by Table 1. As used herein, a three-dimensional structure can also be a most probable, or significant, fit with a set of atomic coordinates. According to the present invention, a most probable or significant fit refers to the fit that a particular Receptor-Ligand Complex has with a set of atomic coordinates derived from that particular Receptor-Ligand Complex. Such atomic coordinates can be derived, for example, from the crystal structure of the protein such as the coordinates determined for the Receptor-Ligand Complex structure provided herein, or from a model of the structure of the protein. For example, the three-dimensional structure of a dimeric protein, including a naturally occurring or recombinantly produced EphB4 receptor protein in complex with ephrinB2, substantially conforms to and is a most probable fit, or significant fit, with the atomic coordinates of Table 1. The three-dimensional crystal structure of the Receptor-Ligand Complex may comprise the atomic coordinates of Table 1. Also as an example, the three-dimensional structure of another Receptor-Ligand Complex would be understood by one of skill in the art to substantially conform to the atomic coordinates of Table 1. This definition can be applied to the other EphB4 receptor proteins in a similar manner.  
         [0029]     For example, the structure of the EphB4 receptor establishes the general architecture of the EphB receptor family. Accordingly, in some configurations, EphB4 receptor protein sequence homology across eukaryotes can be used as a basis to predict the structure of such receptors, in particular the structure for such receptor-ligand binding sites and other conserved regions.  
         [0030]     In various aspects of the present invention, a structure of a Receptor-Ligand Complex substantially conforms to the atomic coordinates represented in Table 1. Such values as listed in Table 1 can be interpreted by one of skill in the art. In other aspects, a three-dimensional structure of a Receptor-Ligand Complex substantially conforms to the three-dimensional coordinates represented in Table 1. In other aspects, a three-dimensional structure of a Receptor-Ligand Complex is a most probable fit with the three-dimensional coordinates represented in Table 1. Methods to determine a substantially conforming and probable fit are within the expertise of skill in the art and are described herein in the Examples section.  
         [0031]     A Receptor-Ligand Complex that has a three-dimensional structure which substantially conforms to the atomic coordinates represented by Table 1 includes an EphB4 receptor protein having an amino acid sequence that is at least about 25%, 26%, 27%, 28%, 29%, 30%, 31%, 32%, 33%, 34%, 35%, 36%, 37%, 38%, 39%, 40%, 41%, 42%, 43%, 44%, 45%, 46%, 47%, 48%, 49%, 50%, 51%, 52%, 53%, 54%, 55%, 56%, 57%, 58%, 59%, 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to an amino acid sequence of a human EphB4 receptor protein, in particular an amino acid sequence having SEQ ID NO: 4, across the full-length of the EphB4 receptor sequence. A sequence alignment program such as BLAST (available from the National Institutes of Health Internet web site http://www.ncbi.nlm.nih.gov/BLAST) may be used by one of skill in the art to compare sequences of an EphB receptor to the EphB4 receptor.  
         [0032]     A three-dimensional structure of any Receptor-Ligand Complex can be modeled using methods generally known in the art based on information obtained from analysis of a Receptor-Ligand Complex crystal, and from other Receptor-Ligand Complex structures which are derived from a Receptor-Ligand Complex crystal. The Examples section below discloses the production of a Receptor-Ligand Complex crystal, in particular a truncated EphB4 receptor having SEQ ID NO: 2 or 3 complexed with ephrinB2 (SEQ ID NO: 6), and a model of a Receptor-Ligand Complex, in particular a truncated EphB4 receptor having SEQ ID NO: 2 or 3 complexed with ephrinB2, using methods generally known in the art based on the information obtained from analysis of a Receptor-Ligand Complex crystal.  
         [0033]     An aspect of the present invention comprises using the three-dimensional structure of a crystalline Receptor-Ligand Complex to derive the three-dimensional structure of another Receptor-Ligand Complex. Therefore, the crystalline EphB4 receptor complexed with ephrinB2 (SEQ ID NO: 6), and the three-dimensional structure of EphB4 complexed with ephrinB2 permits one of ordinary skill in the art to now derive the three-dimensional structure, and models thereof, of another Receptor-Ligand Complex having highly specific EphB4 binding characteristics. The derivation of the structure of such Receptor-Ligand Complexes can now be achieved even in the absence of having crystal structure data for such other Receptor-Ligand Complexes, and when the crystal structure of another Receptor-Ligand Complex is available, the modeling of the three-dimensional structure of the new Receptor-Ligand Complex can be refined using the knowledge already gained from the Receptor-Ligand Complex structure.  
         [0034]     In some configurations of the present teachings, the absence of crystal structure data for other Receptor-Ligand Complexes, the three-dimensional structures of other Receptor-Ligand Complexes can be modeled, taking into account differences in the amino acid sequence of the other Receptor-Ligand Complex. Moreover, the present invention allows for structure-based drug design of compounds which affect the activity of virtually any EphB receptor, and particularly, of EphB4.  
         [0035]     One aspect of the present invention includes a three-dimensional structure of a Receptor-Ligand Complex, in which the atomic coordinates of the Receptor-Ligand Complex are generated by the method comprising: (a) providing an EphB4 receptor complexed with ephrinB2 in crystalline form; (b) generating an electron-density map of the crystalline EphB4 receptor complexed with ephrinB2; and (c) analyzing the electron-density map to produce the atomic coordinates. For example, the structure of human EphB4 receptor in complex with ephrinB2 (SEQ ID NO: 6) is provided herein.  
         [0036]     The present invention also provides a three-dimensional structure of the EphB4 receptor protein complexed with ephrinB2 (SEQ ID NO: 6), can be used to derive a model of the three-dimensional structure of another Receptor-Ligand Complex (i.e., a structure to be modeled). As used herein, a “structure” of a protein refers to the components and the manner of arrangement of the components to constitute the protein. As used herein, the term “model” refers to a representation in a tangible medium of the three-dimensional structure of a protein, polypeptide or peptide. For example, a model can be a representation of the three-dimensional structure in an electronic file, on a computer screen, on a piece of paper (i.e., on a two dimensional medium), and/or as a ball-and-stick figure. Physical three-dimensional models are tangible and include, but are not limited to, stick models and space-filling models. The phrase “imaging the model on a computer screen” refers to the ability to express (or represent) and manipulate the model on a computer screen using appropriate computer hardware and software technology known to those skilled in the art. Such technology is available from a variety of sources including, for example, Accelrys, Inc. (San Diego, Calif.). The phrase “providing a picture of the model” refers to the ability to generate a “hard copy” of the model. Hard copies include both motion and still pictures. Computer screen images and pictures of the model can be visualized in a number of formats including space-filling representations, α-carbon traces, ribbon diagrams and electron density maps.  
         [0037]     Suitable target Receptor-Ligand Complex structures to model using a method of the present invention include any EphB receptor protein, polypeptide or peptide that is substantially structurally related to an EphB4 receptor protein complexed with ephrinB2. In various embodiments, a target Receptor-Ligand Complex structure that is substantially structurally related to an EphB4 receptor protein includes a target Receptor-Ligand Complex structure having an amino acid sequence that is at least about 25%, 26%, 27%, 28%, 29%, 30%, 31%, 32%, 33%, 34%, 35%, 36%, 37%, 38%, 39%, 40%, 41%, 42%, 43%, 44%, 45%, 46%, 47%, 48%, 49%, 50%, 51%, 52%, 53%, 54%, 55%, 56%, 57%, 58%, 59%, 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to an amino acid sequence of a human EphB4 receptor protein, in particular an amino acid sequence having SEQ ID NO: 4, across the full-length of the EphB4 receptor sequence when using, for example, a sequence alignment program such as BLAST (supra). In various aspects of the present invention, target Receptor-Ligand Complex structures to model include proteins comprising amino acid sequences that are at least about 50%, 51%, 52%, 53%, 54%, 55%, 56%, 57%, 58%, 59%, 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to amino acid sequence of a truncated EphB4 receptor, EphB4(17-196), having SEQ ID NO: 2 or EphB4 17-198, having SEQ ID NO: 3, when comparing suitable regions of the sequence, such as the amino acid sequence for an ephrin binding site of any one of the amino acid sequences, when using an alignment program such as BLAST (supra) to align the amino acid sequences.  
         [0038]     According to the present invention, a structure can be modeled using techniques generally described by, for example, Sali, Current Opinions in Biotechnology, vol. 6, pp. 437-451, 1995, and algorithms can be implemented in program packages such as Insight II, available from Accelerys (San Diego, Calif.). Use of Insight II HOMOLOGY requires an alignment of an amino acid sequence of a known structure having a known three-dimensional structure with an amino acid sequence of a target structure to be modeled. The alignment can be a pairwise alignment or a multiple sequence alignment including other related sequences (for example, using the method generally described by Rost, Meth. Enzymol., vol. 266, pp. 525-539, 1996) to improve accuracy. Structurally conserved regions can be identified by comparing related structural features, or by examining the degree of sequence homology between the known structure and the target structure. Certain coordinates for the target structure are assigned using known structures from the known structure. Coordinates for other regions of the target structure can be generated from fragments obtained from known structures such as those found in the Protein Data Bank. Conformation of side chains of the target structure can be assigned with reference to what is sterically allowable and using a library of rotamers and their frequency of occurrence (as generally described in Ponder and Richards, J. Mol. Biol., vol. 193, pp. 775-791, 1987). The resulting model of the target structure, can be refined by molecular mechanics to ensure that the model is chemically and conformationally reasonable.  
         [0039]     Accordingly, one embodiment of the present invention is a method to derive a model of the three-dimensional structure of a target Receptor-Ligand Complex structure, the method comprising the steps of: (a) providing an amino acid sequence of a Receptor-Ligand Complex and an amino acid sequence of a target ligand-complexed EphB receptor; (b) identifying structurally conserved regions shared between the Receptor-Ligand Complex amino acid sequence and the target ligand-complexed EphB4 receptor amino acid sequence; (c) determining atomic coordinates for the target ligand-complexed EphB4 receptor by assigning said structurally conserved regions of the target ligand-complexed EphB4 receptor to a three-dimensional structure using a three-dimensional structure of a Receptor-Ligand Complex based on atomic coordinates that substantially conform to the atomic coordinates represented in Table 1, to derive a model of the three-dimensional structure of the target ligand-complexed EphB4 receptor amino acid sequence. A model according to the present invention has been previously described herein. In one aspect, the model comprises a computer model. The method can further comprise the step of electronically simulating the structural assignments to derive a computer model of the three-dimensional structure of the target ligand-complexed EphB4 receptor amino acid sequence.  
         [0040]     Another embodiment of the present invention is a method to derive a computer model of the three-dimensional structure of a target ephrinB2-complexed EphB4 receptor structure for which a crystal has been produced (referred to herein as a “crystallized target structure”). A suitable method to produce such a model includes the method comprising molecular replacement. Methods of molecular replacement are generally known by those of skill in the art and are performed in a software program including, for example, X-PLOR available from Accelerys (San Diego, Calif.). In various aspects, a crystallized target ligand-complexed EphB receptor structure useful in a method of molecular replacement according to the present invention has an amino acid sequence that is at least about 25%, 26%, 27%, 28%, 29%, 30%, 31%, 32%, 33%, 34%, 35%, 36%, 37%, 38%, 39%, 40%, 41%, 42%, 43%, 44%, 45%, 46%, 47%, 48%, 49%, 50%, 51%, 52%, 53%, 54%, 55%, 56%, 57%, 58%, 59%, 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of the search structure (e.g., human EphB4), when the two amino acid sequences are compared using an alignment program such as BLAST (supra). A suitable search structure of the present invention includes a Receptor-Ligand Complex having a three-dimensional structure that substantially conforms with the atomic coordinates listed in Table 1.  
         [0041]     Another aspect of the present invention is a method to determine a three-dimensional structure of a target Receptor-Ligand Complex structure, in which the three-dimensional structure of the target Receptor-Ligand Complex structure is not known. Such a method is useful for identifying structures that are related to the three-dimensional structure of a Receptor-Ligand Complex based only on the three-dimensional structure of the target structure. For example, the present method enables identification of structures that do not have high amino acid identity with an EphB4 receptor protein but which share three-dimensional structure similarities of a ligand-complexed EphB4 receptor. In various aspects of the present invention, a method to determine a three-dimensional structure of a target Receptor-Ligand Complex structure comprises: (a) providing an amino acid sequence of a target structure, wherein the three-dimensional structure of the target structure is not known; (b) analyzing the pattern of folding of the amino acid sequence in a three-dimensional conformation by fold recognition; and (c) comparing the pattern of folding of the target structure amino acid sequence with the three-dimensional structure of a Receptor-Ligand Complex to determine the three-dimensional structure of the target structure, wherein the three-dimensional structure of the Receptor-Ligand Complex substantially conforms to the atomic coordinates represented in Table 1. For example, methods of fold recognition can include the methods generally described in Jones, Curr. Opinion Struc. Biol., vol. 7, pp. 377-387, 1997. Such folding can be analyzed based on hydrophobic and/or hydrophilic properties of a target structure.  
         [0042]     One aspect of the present invention includes a three-dimensional computer image of the three-dimensional structure of a Receptor-Ligand Complex. In one aspect, a computer image is created to a structure which substantially conforms with the three-dimensional coordinates listed in Table 1. A computer image of the present invention can be produced using any suitable software program, including, but not limited to, Pymol available from DeLano Scientific, LLC (South San Francisco, Calif.). Suitable computer hardware useful for producing an image of the present invention are known to those of skill in the art.  
         [0043]     Another aspect of the present invention relates to a computer-readable medium encoded with a set of three-dimensional coordinates represented in Table 1, wherein, using a graphical display software program, the three-dimensional coordinates create an electronic file that can be visualized on a computer capable of representing said electronic file as a three-dimensional image. Yet another aspect of the present invention relates to a computer-readable medium encoded with a set of three-dimensional coordinates of a three-dimensional structure which substantially conforms to the three-dimensional coordinates represented in Table 1, wherein, using a graphical display software program, the set of three-dimensional coordinates create an electronic file that can be visualized on a computer capable of representing said electronic file as a three-dimensional image.  
         [0044]     The present invention also includes a three-dimensional model of the three-dimensional structure of a target structure, such a three-dimensional model being produced by the method comprising: (a) providing an amino acid sequences of an EphB4 receptor comprised by a Receptor-Ligand Complex and an amino acid sequence of a target Receptor-Ligand Complex structure; (b) identifying structurally conserved regions shared between the EphB4 receptor amino acid sequence and the amino acid sequence comprised by the target Receptor-Ligand Complex structure; (c) determining atomic coordinates for the target Receptor-Ligand Complex by assigning the structurally conserved regions of the target Receptor-Ligand Complex to a three-dimensional structure using a three-dimensional structure of the EphB4 receptor comprised by a Receptor-Ligand Complex based on atomic coordinates that substantially conform to the atomic coordinates represented in Table 1 to derive a model of the three-dimensional structure of the target Receptor-Ligand Complex. In one aspect, the model comprises a computer model.  
         [0045]     Another isolated EphB receptor protein can be used with the methods of the present invention. An isolated EphB receptor protein can be isolated from its natural milieu or produced using recombinant DNA technology (e.g., polymerase chain reaction (PCR) amplification, cloning) or chemical synthesis. To produce recombinant EphB receptor protein, a nucleic acid molecule encoding EphB receptor protein (e.g., SEQ ID NO: 5) can be inserted into any vector capable of delivering the nucleic acid molecule into a host cell. A nucleic acid molecule of the present invention can encode any portion of an EphB receptor protein, in various aspects a full-length EphB receptor protein, and in various aspects a soluble or truncated form of EphB4 receptor protein (i.e., a form of EphB4 receptor protein capable of being secreted by a cell that produces such protein). A suitable nucleic acid molecule to include in a recombinant vector, and particularly in a recombinant molecule, includes a nucleic acid molecule encoding a protein having the amino acid sequence represented by SEQ ID NOs: 2 or 3 and SEQ ID NO: 4.  
         [0046]     A recombinant vector can be either RNA or DNA, either prokaryotic or eukaryotic, and typically is a virus or a plasmid. In various aspects, a nucleic acid molecule encoding an EphB4 receptor protein is inserted into a vector comprising an expression vector to form a recombinant molecule. As used herein, an expression vector is a DNA or RNA vector that is capable of transforming a host cell and of affecting expression of a specified nucleic acid molecule. Expression vectors of the present invention include any vectors that function (i.e., direct gene expression) in recombinant cells of the present invention, including in bacterial, fungal, endoparasite, insect, other animal, and plant cells.  
         [0047]     An expression vector can be transformed into any suitable host cell to form a recombinant cell. A suitable host cell includes any cell capable of expressing a nucleic acid molecule inserted into the expression vector. For example, a prokaryotic expression vector can be transformed into a bacterial host cell. One method to isolate EphB4 receptor protein useful for producing ligand-complexed EphB4 receptor crystals includes recovery of recombinant proteins from cell cultures of recombinant cells expressing such EphB4 receptor protein.  
         [0048]     EphB4 receptor proteins of the present invention can be purified using a variety of standard protein purification techniques, such as, but not limited to, affinity chromatography, ion exchange chromatography, filtration, electrophoresis, hydrophobic interaction chromatography, gel filtration chromatography, reverse phase chromatography, chromatofocusing and differential solubilization. In various aspects of the present invention, an EphB4 receptor protein is purified in such a manner that the protein is purified sufficiently for formation of crystals useful for obtaining information related to the three-dimensional structure of a Receptor-Ligand Complex. In some aspects, a composition of EphB4 receptor protein is about 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% pure.  
         [0049]     Another embodiment of the present invention includes a composition comprising a Receptor-Ligand Complex in a crystalline form (i.e., Receptor-Ligand Complex crystals). As used herein, the terms “crystalline Receptor-Ligand Complex” and “Receptor-Ligand Complex crystal” both refer to crystallized a Receptor-Ligand Complex and are intended to be used interchangeably. In various aspects of the present invention, a crystalline Receptor-Ligand Complex is produced using the crystal formation method described in the Examples.  
         [0050]     In particular, the present invention includes a composition comprising EphB4 receptor complexed with ephrinB2 in a crystalline form (i.e., ephrinB2-complexed EphB4 crystals). As used herein, the terms “crystalline ephrinB2-complexed EphB4” and “ephrinB2-complexed EphB4 crystal” both refer to crystallized EphB4 receptor complexed with ephrinB2 and are intended to be used interchangeably. In various aspects of the present invention, a crystal ephrinB2-complexed EphB4 is produced using the crystal formation method described in the Examples. In some aspects, a composition of the present invention includes ephrinB2-complexed EphB4 molecules arranged in a crystalline manner in a space group P4 1  so as to form a unit cell of dimensions a=81.09 Å, b=81.09 Å, and c=50.95 Å. A suitable crystal of the present invention provides X-ray diffraction data for determination of atomic coordinates of the ephrinB2-complexed EphB4 to a resolution of about 2.0 Å, and in some aspects about 1.8 Å, and in other aspects at about 1.6 Å.  
         [0051]     According to an aspect of the present invention, crystalline Receptor-Ligand Complex can be used to determine the ability of a compound of the present invention to bind to an EphB4 receptor in a manner predicted by a structure based drug design method of the present invention. In various aspects of the present invention, a Receptor-Ligand Complex crystal is soaked in a solution containing a chemical compound of the present invention. Binding of the chemical compound to the crystal is then determined by methods standard in the art.  
         [0052]     One aspect of the present invention is a therapeutic composition. A therapeutic composition of the present invention comprises one or more therapeutic compounds. In one aspect, a therapeutic composition is provided that is capable of antagonizing the EphB4 receptor. For example, a therapeutic composition of the present invention can inhibit (i.e., prevent, block) binding of an EphB4 receptor on a cell having an EphB4 receptor (e.g., human cells) to a, e.g., ephrinB2 or ephrinB2 analog by interfering with the ligand binding domain of an EphB4 receptor. As used herein, the term “ligand binding domain” refers to the region of a molecule to which another molecule specifically binds.  
         [0053]     Suitable inhibitory compounds of the present invention are compounds that interact directly with an EphB4 receptor protein or truncated EphB4 receptor protein (e.g., SEQ ID NOs: 2 or 3), thereby inhibiting the binding of ephrin-B2 to an EphB4 receptor by blocking the ligand binding domain of an EphB4 receptor (referred to herein as substrate analogs). An EphB4 receptor substrate analog refers to a compound that interacts with (e.g., binds to, associates with, modifies) the ligand binding domain of an EphB4 receptor. An EphB4 receptor substrate analog can, for example, comprise a chemical compound that mimics a polypeptide having SEQ ID NO: 6, truncated polypeptides comprised by SEQ ID NO: 6, or that binds specifically to the ephrin binding globular domain of an EphB4 receptor. Particularly, a substrate analog can comprise the G-H loop of ephrinB2 (SEQ ID NO: 7). Additionally, amino acids 120 through 127 of SEQ ID NO: 6 are useful in various aspects. In various aspects, an EphB4 receptor substrate analog useful in the present invention has an amino acid sequence that is at least about 25%, 26%, 27%, 28%, 29%, 30%, 31%, 32%, 33%, 34%, 35%, 36%, 37%, 38%, 39%, 40%, 41%, 42%, 43%, 44%, 45%, 46%, 47%, 48%, 49%, 50%, 51%, 52%, 53%, 54%, 55%, 56%, 57%, 58%, 59%, 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 7 and amino acids 120 through 127 of SEQ ID NO: 6.  
         [0054]     According to the present invention, suitable therapeutic compounds of the present invention include peptides or other organic molecules, and inorganic molecules. Suitable organic molecules include small organic molecules. In various aspects, a therapeutic compound of the present invention is not harmful (e.g., toxic) to an animal when such compound is administered to an animal. Peptides refer to a class of compounds that is small in molecular weight and yields two or more amino acids upon hydrolysis. A polypeptide is comprised of two or more peptides. As used herein, a protein is comprised of one or more polypeptides. Suitable therapeutic compounds to design include peptides composed of “L” and/or “D” amino acids that are configured as normal or retroinverso peptides, peptidomimetic compounds, small organic molecules, or homo- or hetero-polymers thereof, in linear or branched configurations.  
         [0055]     Therapeutic compounds of the present invention can be designed using structure based drug design. Structure based drug design refers to the use of computer simulation to predict a conformation of a peptide, polypeptide, protein, or conformational interaction between a peptide or polypeptide, and a therapeutic compound. In the present teachings, knowledge of the three-dimensional structure of the EphB4 ligand binding domain of an EphB4 receptor when bound with ephrinB2 provide one of skill in the art the ability to design a therapeutic compound that binds to EphB4 receptors, is stable and results in inhibition of a biological response, such as tumorigenesis. For example, knowledge of the three-dimensional structure of the EphB4 ligand binding domain of an EphB4 receptor in complex with ephrinB2 provides to a skilled artisan the ability to design a ligand or an analog of a ligand which can function as a substrate or ligand of an EphB4 receptor.  
         [0056]     Suitable structures and models useful for structure-based drug design are disclosed herein. Models of target structures to use in a method of structure-based drug design include models produced by any modeling method disclosed herein, such as, for example, molecular replacement and fold recognition related methods. In some aspects of the present invention, structure based drug design can be applied to a structure of EphB4 in complex with ephrinB2 (SEQ ID NO: 6), and to a model of a target EphB receptor structure.  
         [0057]     One embodiment of the present invention is a method for designing a drug which interferes with an activity of an EphB4 receptor. In various configurations, the method comprises providing a three-dimensional structure of a Receptor-Ligand Complex comprising the EphB4 receptor and at least one ligand of the receptor; and designing a chemical compound which is predicted to bind to the EphB4 receptor. The designing can comprise using physical models, such as, for example, ball-and-stick representations of atoms and bonds, or on a digital computer equipped with molecular modeling software. In some configurations, these methods can further include synthesizing the chemical compound, and evaluating the chemical compound for ability to interfere with an activity of the EphB4 receptor.  
         [0058]     Suitable three-dimensional structures of a Receptor-Ligand Complex and models to use with the present method are disclosed herein. According to the present invention, designing a compound can include creating a new chemical compound or searching databases of libraries of known compounds (e.g., a compound listed in a computational screening database containing three-dimensional structures of known compounds). Designing can also include simulating chemical compounds having substitute moieties at certain structural features. In some configurations, designing can include selecting a chemical compound based on a known function of the compound. In some configurations designing can comprise computational screening of one or more databases of compounds in which three-dimensional structures of the compounds are known. In these configurations, a candidate compound can be interacted virtually (e.g., docked, aligned, matched, interfaced) with the three-dimensional structure of a Receptor-Ligand Complex by computer equipped with software such as, for example, the AutoDock software package, (The Scripps Research Institute, La Jolla, Calif.) or described by Humblet and Dunbar, Animal Reports in Medicinal Chemistry, vol. 28, pp. 275-283, 1993, M Venuti, ed., Academic Press. Methods for synthesizing candidate chemical compounds are known to those of skill in the art.  
         [0059]     Various other methods of structure-based drug design are disclosed in references such as Maulik et al., 1997,  Molecular Biotechnology: Therapeutic Applications and Strategies , Wiley-Liss, Inc., which is incorporated herein by reference in its entirety. Maulik et al. disclose, for example, methods of directed design, in which the user directs the process of creating novel molecules from a fragment library of appropriately selected fragments; random design, in which the user uses a genetic or other algorithm to randomly mutate fragments and their combinations while simultaneously applying a selection criterion to evaluate the fitness of candidate ligands; and a grid-based approach in which the user calculates the interaction energy between three-dimensional structures and small fragment probes, followed by linking together of favorable probe sites.  
         [0060]     In one aspect, a chemical compound of the present invention that binds to the ligand binding domain of a Receptor-Ligand Complex can be a chemical compound having chemical and/or stereochemical complementarity with an EphB4 receptor, e.g., an EphB4 receptor or ligand such as, for example, ephrinB2. In particular, the amino acid sequence of SEQ ID NO: 7, amino acids 120 through 127 of SEQ ID NO: 6, and analogs thereof can be complimentary. In some configurations, a chemical compound that binds to the ligand binding domain of an EphB4 receptor can associate with an affinity of at least about 10 −6  M, at least about 10 −7  M, or at least about 10 −8  M.  
         [0061]     Several sites of an EphB4 receptor can be targeted for structure based drug design. These sites include, in non-limiting example residues which contact ephrin-B2 or a polypeptide having SEQ ID NO: 1, e.g., EphB4 D-E and J-K loops; Leu-48, Cys-61, Leu-95, Ser-99 Leu-100, Pro-101, Thr-147, Lys-149, Ala-155, and Cys-184 of SEQ ID NO: 6. Conversely, the structure based drug design can be based upon the sites of the ligand which bind to the EphB4 receptor, e.g., Phe-120, Pro-122, Leu-124, Trp-125, and Leu-127 of ephrinB2.  
         [0062]     Drug design strategies as specifically described above with regard to residues and regions of the ligand-complexed EphB4 receptor crystal can be similarly applied to the other EphB structures, including other EphB receptors disclosed herein. One of ordinary skill in the art, using the art recognized modeling programs and drug design methods, many of which are described herein, can modify the EphB4 design strategy according to differences in amino acid sequence. For example, this strategy can be used to design compounds which regulate a function of the EphB4 receptor in EphB receptors. In addition, one of skill in the art can use lead compound structures derived from one EphB receptor, such as the EphB4 receptor, and take into account differences in amino acid residues in other EphB4 receptors.  
         [0063]     In the present method of structure-based drug design, it is not necessary to align a candidate chemical compound (i.e., a chemical compound being analyzed in, for example, a computational screening method of the present invention) to each residue in a target site. Suitable candidate chemical compounds can align to a subset of residues described for a target site. In some configurations of the present invention, a candidate chemical compound can comprise a conformation that promotes the formation of covalent or noncovalent crosslinking between the target site and the candidate chemical compound. In certain aspects, a candidate chemical compound can bind to a surface adjacent to a target site to provide an additional site of interaction in a complex. For example, when designing an antagonist (i.e., a chemical compound that inhibits the binding of ephrinB2 to an EphB4 receptor by blocking a ligand binding domain or interface), the antagonist can be designed to bind with sufficient affinity to the binding site or to substantially prohibit a ligand from binding to a target area. It will be appreciated by one of skill in the art that it is not necessary that the complementarity between a candidate chemical compound and a target site extend over all residues specified here.  
         [0064]     In various aspects, the design of a chemical compound possessing stereochemical complementarity can be accomplished by means of techniques that optimize, chemically or geometrically, the “fit” between a chemical compound and a target site. Such techniques are disclosed by, for example, Sheridan and Venkataraghavan, Acc. Chem. Res., vol. 20, p. 322, 1987: Goodford, J. Med. Chem., vol. 27, p. 557, 1984; Beddell, Chem. Soc. Reviews, vol. 279, 1985; Hol, Angew. Chem., vol. 25, p. 767, 1986; and Verlinde and Hol, Structure, vol. 2, p. 577, 1994, each of which are incorporated by this reference herein in their entirety.  
         [0065]     Some embodiments of the present invention for structure-based drug design comprise methods of identifying a chemical compound that complements the shape of an EphB4 receptor, particularly one that substantially conforms to the atomic coordinates of Table 1, or a structure that is related to an EphB4 receptor. Such method is referred to herein as a “geometric approach”. In a geometric approach of the present invention, the number of internal degrees of freedom (and the corresponding local minima in the molecular conformation space) can be reduced by considering only the geometric (hard-sphere) interactions of two rigid bodies, where one body (the active site) contains “pockets” or “grooves” that form binding sites for the second body (the complementing molecule, such as a ligand).  
         [0066]     The geometric approach is described by Kuntz et al., J. Mol. Biol., vol. 161, p. 269, 1982, which is incorporated by this reference herein in its entirety. The algorithm for chemical compound design can be implemented using a software program such as AutoDock, available from the The Scripps Research Institute (La Jolla, Calif.). One or more extant databases of crystallographic data (e.g., the Cambridge Structural Database System maintained by University Chemical Laboratory, Cambridge University, Lensfield Road, Cambridge CB2 IEW, U.K. or the Protein Data Bank maintained by Rutgers University) can then be searched for chemical compounds that approximate the shape thus defined. Chemical compounds identified by the geometric approach can be modified to satisfy criteria associated with chemical complementarity, such as hydrogen bonding, ionic interactions or Van der Waals interactions.  
         [0067]     In some embodiments, a therapeutic composition of the present invention can comprise one or more therapeutic compounds. A therapeutic composition can further comprise other compounds capable of inhibiting an EphB4 receptor. A therapeutic composition of the present invention can be used to treat disease in an animal such as, for example, a human in need of treatment by administering such composition to the human. Non-limiting examples of animals to treat include mammals, reptiles and birds, companion animals, food animals, zoo animals and other economically relevant animals (e.g., race horses and animals valued for their coats, such as minks). Additional animals to treat include dogs, cats, horses, cattle, sheep, swine, chickens, turkeys. Accordingly, in some aspects, animals to treat include humans.  
         [0068]     A therapeutic composition of the present invention can also include an excipient, an adjuvant and/or carrier. Suitable excipients include compounds that the animal to be treated can tolerate. Examples of such excipients include water, saline, Ringer&#39;s solution, dextrose solution, Hank&#39;s solution, and other aqueous physiologically balanced salt solutions. Nonaqueous vehicles, such as fixed oils, sesame oil, ethyl oleate, or triglycerides may also be used. Other useful formulations include suspensions containing viscosity enhancing agents, such as sodium carboxymethylcellulose, sorbitol, or dextran. Excipients can also contain minor amounts of additives, such as substances that enhance isotonicity and chemical stability. Examples of buffers include phosphate buffer, bicarbonate buffer and Tris buffer, while examples of preservatives include thimerosal, o-cresol, formalin and benzyl alcohol. Standard formulations can either be liquid injectables or solids which can be taken up in a suitable liquid as a suspension or solution for injection. Thus, in a non-liquid formulation, the excipient can comprise dextrose, human serum albumin, preservatives, etc., to which sterile water or saline can be added prior to administration.  
         [0069]     In one embodiment of the present invention, a therapeutic composition can include a carrier. Carriers include compounds that increase the half-life of a therapeutic composition in the treated animal. Suitable carriers include, but are not limited to, polymeric controlled release vehicles, biodegradable implants, liposomes, bacteria, viruses, other cells, oils, esters, and glycols.  
         [0070]     Acceptable protocols to administer therapeutic compositions of the present invention in an effective manner include individual dose size, number of doses, frequency of dose administration, and mode of administration. Determination of such protocols can be accomplished by those skilled in the art. Modes of administration can include, but are not limited to, subcutaneous, intradermal, intravenous, intranasal, oral, transdermal, intraocular and intramuscular routes.  
         [0071]     In yet another embodiment, a method is provided for crystallizing an EphB4 receptor which includes providing an EphB4 receptor in contact with a polypeptide having SEQ ID NO: 1, followed by contacting the EphB4 receptor in contact with the polypeptide with a therapeutic compound as provided above, wherein the EphB4 receptor in contact with the polypeptide and the compound forms an EphB4 receptor crystal.  
         [0072]     In another embodiment, a composition is provided comprising EphB4 receptor, a ligand, and a therapeutic compound as provided above. The EphB4 receptor can be a polypeptide having SEQ ID NO: 2 or 3. The EphB4 receptor can also consist essentially of EphB4 D-E and J-K loops or Leu-48, Cys-61, Leu-95, Ser-99 Leu-100, Pro-101, Thr-147, Lys-149, Ala-155, and Cys-184 of SEQ ID NO: 6. In certain embodiments, the EphB4 receptor can be a human EphB4 receptor.  
         [0073]     In certain embodiments, the ligand can be a polypeptide having SEQ ID NO: 7 and amino acids 120 through 127 of SEQ ID NO: 6. In other embodiments, the ligand can be a polypeptide having at least 50%, 75% or 90% sequence identity to a polypeptide selected from the group consisting of polypeptides having SEQ ID NO: 7 and amino acids 120 through 127 of SEQ ID NO: 6.  
         [0074]     In some aspects, the present teachings include mutants of EphB4. In various configurations, these mutants can include at least one amino acid substitution, at least one amino acid addition, and/or at least one amino acid deletion. Such mutant EphB4 polypeptides and proteins can be constructed by methods well known to skilled artisans, such as site-directed mutagenesis. In some configurations, an EphB4 mutant can exhibit lower binding affinity (compared to wild type) for an EphB4 ligand such as EphrinB2, a TNYL-RAW peptide, or a labeled, e.g., fluorescently tagged, TNYL-RAW peptide. In some aspects, the binding affinity to an EphB4 ligand can be lower than that of wild type EphB4 (wtEphB4), without altering the binding specificity of the EphB4. Some non-limiting examples of EphB4 mutants of these aspects include T147F (i.e., threonine-147 to phenylalanine), K149Q (i.e., lysine-149 to glutamine), and A186S (i.e., alanine-186 to serine) as well as those found in  FIG. 4 . Accordingly, the dynamic range of binding of an EphB4 ligand to a mutant EphB4 can be greater than that of binding of an EphB4 ligand to wtEphB4. In some configurations, the dynamic range can be greater than about 2-fold (i.e., the dynamic range for a wtEphB4-ligand binding assay), such as, without limitation, a 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and 12-fold dynamic range.  
         [0075]     In some aspects, a mutant EphB4 can be used in a screening assay for an EphB4 ligand, such as an EphB4 agonist or an EphB4 inhibitor. In a non-limiting example, an assay can comprise a fluorescence polarization (FP) assay using a fluorescent ligand such as a TNYL-RAW peptide labeled with a fluorophore such as Alexa-532 (Invitrogen). In various configurations, an assay can comprise contacting a complex comprising a mutant EphB4 and a fluorescent ligand with a candidate EphB4 ligand, and measuring a shift in the FP of the fluorescent ligand (Park, S. H., and Raines, R. T., Methods Mol. Biol. 261: 161-166, 2004). In some configurations, a mutant EphB4 can show a lower specificity to a ligand such as EphrinB2 or a fluorescent TNYL-RAW peptide. A shift in FP in such assays can indicate that a candidate EphB4 ligand binds to the EphB4. A compound identified by such a screening assay can be further tested, e.g., for pharmacological effectiveness and toxicity, using standard cell biological, biochemical and pharmacological tests well known to skilled artisans. Such assays can be used individually with candidate molecules, or at any scale of screening, such as, without limitation, high-throughput screening in which several thousand compounds can be rapidly tested for activity as ligands for EphB4.  
                                                                       TABLE 1                       Protein Databank Coordinates       of EphB4 Receptor Complexed ephrinB2                                REMARK 3 PROGRAM: REFMAC 5.2.0019       REMARK 3 AUTHORS: MURSHUDOV, VAGIN, DODSON       REMARK 3       REMARK 3 REFINEMENT TARGET: MAXIMUM LIKELIHOOD       REMARK 3       REMARK 3 DATA USED IN REFINEMENT.       REMARK 3 RESOLUTION RANGE HIGH (ANGSTROMS): 1.91       REMARK 3 RESOLUTION RANGE LOW (ANGSTROMS): 36.27       REMARK 3 DATA CUTOFF (SIGMA(F)): NONE       REMARK 3 COMPLETENESS FOR RANGE (%): 99.07       REMARK 3 NUMBER OF REFLECTIONS: 24232       REMARK 3       REMARK 3 FIT TO DATA USED IN REFINEMENT.       REMARK 3 CROSS-VALIDATION METHOD: THROUGHOUT       REMARK 3 FREE R VALUE TEST SET SELECTION: RANDOM       REMARK 3 R VALUE (WORKING + TEST SET): 0.26396       REMARK 3 R VALUE (WORKING SET): 0.26082       REMARK 3 FREE R VALUE: 0.32142       REMARK 3 FREE R VALUE TEST SET SIZE (%): 5.1       REMARK 3 FREE R VALUE TEST SET COUNT: 1304       REMARK 3       REMARK 3 FIT IN THE HIGHEST RESOLUTION BIN.       REMARK 3 TOTAL NUMBER OF BINS USED: 20       REMARK 3 BIN RESOLUTION RANGE HIGH: 1.912       REMARK 3 BIN RESOLUTION RANGE LOW: 1.962       REMARK 3 REFLECTION IN BIN (WORKING SET): 1659       REMARK 3 BIN COMPLETENESS (WORKING + TEST) (%): 92.46       REMARK 3 BIN R VALUE (WORKING SET): 0.331       REMARK 3 BIN FREE R VALUE SET COUNT: 94       REMARK 3 BIN FREE R VALUE: 0.413       REMARK 3       REMARK 3 NUMBER OF NON-HYDROGEN ATOMS USED IN       REFINEMENT.       REMARK 3 ALL ATOMS: 2510       REMARK 3       REMARK 3 B VALUES.       REMARK 3 FROM WILSON PLOT (A**2): NULL       REMARK 3 MEAN B VALUE (OVERALL, A**2): 46.363       REMARK 3 OVERALL ANISOTROPIC B VALUE.       REMARK 3 B11 (A**2): −0.18       REMARK 3 B22 (A**2): −0.18       REMARK 3 B33 (A**2): 0.36       REMARK 3 B12 (A**2): 0.00       REMARK 3 B13 (A**2): 0.00       REMARK 3 B23 (A**2): 0.00       REMARK 3       REMARK 3 ESTIMATED OVERALL COORDINATE ERROR.       REMARK 3 ESU BASED ON R VALUE (A): 0.214       REMARK 3 ESU BASED ON FREE R VALUE (A): 0.202       REMARK 3 ESU BASED ON MAXIMUM LIKELIHOOD (A): 0.220       REMARK 3 ESU FOR B VALUES BASED ON MAXIMUM       LIKELIHOOD (A**2): 16.948       REMARK 3       REMARK 3 CORRELATION COEFFICIENTS.       REMARK 3 CORRELATION COEFFICIENT FO-FC: 0.934       REMARK 3 CORRELATION COEFFICIENT FO-FC FREE: 0.893       REMARK 3       REMARK 3 RMS DEVIATIONS FROM IDEAL VALUES COUNT       RMS WEIGHT       REMARK 3 BOND LENGTHS REFINED ATOMS (A): 2577; 0.013;       0.022       REMARK 3 BOND ANGLES REFINED ATOMS (DEGREES): 3512;       1.579; 1.950       REMARK 3 TORSION ANGLES, PERIOD 1 (DEGREES): 323;       7.895; 5.000       REMARK 3 TORSION ANGLES, PERIOD 2 (DEGREES): 109;       37.322; 24.404       REMARK 3 TORSION ANGLES, PERIOD 3 (DEGREES): 406;       20.218; 15.000       REMARK 3 TORSION ANGLES, PERIOD 4 (DEGREES): 9;       14.327; 15.000       REMARK 3 CHIRAL-CENTER RESTRAINTS (A**3): 392; 0.103;       0.200       REMARK 3 GENERAL PLANES REFINED ATOMS (A): 1955;       0.006; 0.020       REMARK 3 NON-BONDED CONTACTS REFINED ATOMS (A):       976; 0.233; 0.200       REMARK 3 NON-BONDED TORSION REFINED ATOMS (A):       1665; 0.309; 0.200       REMARK 3 H-BOND (X . . . Y) REFINED ATOMS (A): 89; 0.168;       0.200       REMARK 3 SYMMETRY VDW REFINED ATOMS (A): 52; 0.228;       0.200       REMARK 3 SYMMETRY H-BOND REFINED ATOMS (A): 9; 0.218;       0.200       REMARK 3       REMARK 3 ISOTROPIC THERMAL FACTOR RESTRAINTS. COUNT RMS WEIGHT       REMARK 3 MAIN-CHAIN BOND REFINED ATOMS (A**2): 1660;       2.151; 3.000       REMARK 3 MAIN-CHAIN ANGLE REFINED ATOMS (A**2): 2588;       3.180; 5.000       REMARK 3 SIDE-CHAIN BOND REFINED ATOMS (A**2): 1065;       4.640; 7.000       REMARK 3 SIDE-CHAIN ANGLE REFINED ATOMS (A**2): 924;       5.442; 9.000       REMARK 3       REMARK 3 NCS RESTRAINTS STATISTICS       REMARK 3 NUMBER OF NCS GROUPS: NULL       REMARK 3       REMARK 3       REMARK 3 TLS DETAILS       REMARK 3 NUMBER OF TLS GROUPS: 2       REMARK 3 ATOM RECORD CONTAINS RESIDUAL B FACTORS       ONLY       REMARK 3       REMARK 3 TLS GROUP: 1       REMARK 3 NUMBER OF COMPONENTS GROUP: 1       REMARK 3 COMPONENTS C SSSEQI TO C SSSEQI       REMARK 3 RESIDUE RANGE: A 9 A 196       REMARK 3 ORIGIN FOR THE GROUP (A): 6.5459 29.3924 −8.9085       REMARK 3 T TENSOR       REMARK 3 T11: −0.0510 T22: −0.0163       REMARK 3 T33: 0.0412 T12: 0.0109       REMARK 3 T13: −0.0201 T23: 0.0639       REMARK 3 L TENSOR       REMARK 3 L11: 1.0238 L22: 1.0652       REMARK 3 L33: 0.1402 L12: −0.0578       REMARK 3 L13: 0.0466 L23: 0.0816       REMARK 3 S TENSOR       REMARK 3 S11: −0.0398 S12: 0.2633 S13: 0.0085       REMARK 3 S21: 0.0822 S22: 0.0447 S23: 0.2172       REMARK 3 S31: −0.0545 S32: 0.0708 S33: −0.0048       REMARK 3       REMARK 3 TLS GROUP: 2       REMARK 3 NUMBER OF COMPONENTS GROUP: 1       REMARK 3 COMPONENTS C SSSEQI TO C SSSEQI       REMARK 3 RESIDUE RANGE: B 31 B 167       REMARK 3 ORIGIN FOR THE GROUP (A): 24.0838 25.2120       12.7894       REMARK 3 T TENSOR       REMARK 3 T11: −0.0009 T22: −0.0420       REMARK 3 T33: −0.0654 T12: 0.0636       REMARK 3 T13: −0.0312 T23: 0.0420       REMARK 3 L TENSOR       REMARK 3 L11: 1.3724 L22: 1.0673       REMARK 3 L33: 2.6076 L12: 0.8437       REMARK 3 L13: 1.4287 L23: 0.6393       REMARK 3 S TENSOR       REMARK 3 S11: 0.1162 S12: 0.1266 S13: −0.1332       REMARK 3 S21: 0.2137 S22: 0.0292 S23: −0.0248       REMARK 3 S31: 0.1770 S32: 0.2825 S33: −0.1455       REMARK 3       REMARK 3       REMARK 3 BULK SOLVENT MODELLING.       REMARK 3 METHOD USED: MASK       REMARK 3 PARAMETERS FOR MASK CALCULATION       REMARK 3 VDW PROBE RADIUS: 1.20       REMARK 3 ION PROBE RADIUS: 0.80       REMARK 3 SHRINKAGE RADIUS: 0.80       REMARK 3       REMARK 3 OTHER REFINEMENT REMARKS:       REMARK 3 HYDROGENS HAVE BEEN ADDED IN THE RIDING       POSITIONS       REMARK 3       SSBOND 1 CYS A 61 CYS A 184       SSBOND 2 CYS A 97 CYS A 107       SSBOND 3 CYS B 65 CYS B 104       SSBOND 4 CYS B 92 CYS B 156       CISPEP 1 PHE A 35 PRO A 36 0.00       CISPEP 2 THR A 127 PRO A 128 0.00       CISPEP 3 ASN A 133 PRO A 134 0.00       CISPEP 4 GLY A 167 PRO A 168 0.00       CISPEP 5 ASP B 90 ARG B 91 0.00       CRYST1 81.085 81.085 50.945 90.00 90.00 90.00 P 41       SCALE1 0.012333 0.000000 0.000000 0.00000       SCALE2 0.000000 0.012333 0.000000 0.00000       SCALE3 0.000000 0.000000 0.019629 0.00000            ATOM   10   N   HIS   A   11   24.448   54.004   −27.877   1.00   49.00   N       ATOM   11   CA   HIS   A   11   23.039   54.322   −27.723   1.00   47.86   C       ATOM   12   CB   HIS   A   11   22.253   53.916   −28.974   1.00   48.48   C       ATOM   13   CG   HIS   A   11   22.560   54.756   −30.174   1.00   46.99   C       ATOM   14   ND1   HIS   A   11   21.891   55.929   −30.454   1.00   47.84   N       ATOM   15   CE1   HIS   A   11   22.369   56.455   −31.566   1.00   44.85   C       ATOM   16   NE2   HIS   A   11   23.333   55.672   −32.016   1.00   48.34   N       ATOM   17   CD2   HIS   A   11   23.473   54.602   −31.163   1.00   49.20   C       ATOM   18   C   HIS   A   11   22.494   53.661   −26.468   1.00   46.86   C       ATOM   19   O   HIS   A   11   22.657   52.455   −26.254   1.00   46.50   O       ATOM   20   N   HIS   A   12   21.858   54.459   −25.620   1.00   44.51   N       ATOM   21   CA   HIS   A   12   21.462   53.973   −24.313   1.00   43.01   C       ATOM   22   CB   HIS   A   12   22.056   54.854   −23.211   1.00   43.91   C       ATOM   23   CG   HIS   A   12   23.320   54.305   −22.635   1.00   46.33   C       ATOM   24   ND1   HIS   A   12   23.372   53.706   −21.396   1.00   47.69   N       ATOM   25   CE1   HIS   A   12   24.605   53.299   −21.160   1.00   52.21   C       ATOM   26   NE2   HIS   A   12   25.351   53.602   −22.207   1.00   51.06   N       ATOM   27   CD2   HIS   A   12   24.569   54.227   −23.145   1.00   49.90   C       ATOM   28   C   HIS   A   12   19.962   53.828   −24.139   1.00   40.46   C       ATOM   29   O   HIS   A   12   19.191   54.727   −24.500   1.00   41.03   O       ATOM   30   N   HIS   A   13   19.556   52.677   −23.624   1.00   39.88   N       ATOM   31   CA   HIS   A   13   18.184   52.506   −23.152   1.00   39.98   C       ATOM   32   CB   HIS   A   13   17.414   51.459   −23.973   1.00   39.69   C       ATOM   33   CG   HIS   A   13   15.982   51.315   −23.562   1.00   40.91   C       ATOM   34   ND1   HIS   A   13   15.410   50.100   −23.255   1.00   43.46   N       ATOM   35   CE1   HIS   A   13   14.154   50.287   −22.890   1.00   36.43   C       ATOM   36   NE2   HIS   A   13   13.895   51.579   −22.942   1.00   39.44   N       ATOM   37   CD2   HIS   A   13   15.021   52.242   −23.359   1.00   38.36   C       ATOM   38   C   HIS   A   13   18.174   52.172   −21.661   1.00   39.78   C       ATOM   39   O   HIS   A   13   18.660   51.131   −21.228   1.00   38.65   O       ATOM   40   N   HIS   A   14   17.617   53.068   −20.866   1.00   38.90   N       ATOM   41   CA   HIS   A   14   17.507   52.802   −19.451   1.00   39.71   C       ATOM   42   CB   HIS   A   14   17.974   54.017   −18.639   1.00   41.36   C       ATOM   43   C   HIS   A   14   16.049   52.499   −19.153   1.00   40.66   C       ATOM   44   O   HIS   A   14   15.159   53.220   −19.604   1.00   38.87   O       ATOM   45   N   HIS   A   15   15.797   51.424   −18.419   1.00   37.90   N       ATOM   46   CA   HIS   A   15   14.455   51.188   −17.913   1.00   39.77   C       ATOM   47   CB   HIS   A   15   13.713   50.239   −18.844   1.00   38.53   C       ATOM   48   CG   HIS   A   15   12.236   50.372   −18.753   1.00   36.65   C       ATOM   49   ND1   HIS   A   15   11.388   49.846   −19.698   1.00   36.72   N       ATOM   50   CE1   HIS   A   15   10.141   50.136   −19.372   1.00   37.69   C       ATOM   51   NE2   HIS   A   15   10.155   50.844   −18.256   1.00   36.35   N       ATOM   52   CD2   HIS   A   15   11.454   51.002   −17.845   1.00   37.33   C       ATOM   53   C   HIS   A   15   14.438   50.663   −16.465   1.00   42.34   C       ATOM   54   O   HIS   A   15   14.945   49.583   −16.197   1.00   45.21   O       ATOM   55   N   HIS   A   16   13.877   51.449   −15.542   1.00   42.50   N       ATOM   56   CA   HIS   A   16   13.849   51.102   −14.115   1.00   44.89   C       ATOM   57   CB   HIS   A   16   13.544   52.349   −13.269   1.00   46.52   C       ATOM   58   CG   HIS   A   16   14.588   53.417   −13.375   1.00   54.62   C       ATOM   59   ND1   HIS   A   16   14.398   54.577   −14.100   1.00   57.87   N       ATOM   60   CE1   HIS   A   16   15.486   55.323   −14.023   1.00   52.34   C       ATOM   61   NE2   HIS   A   16   16.378   54.684   −13.286   1.00   53.86   N       ATOM   62   CD2   HIS   A   16   15.843   53.488   −12.870   1.00   51.85   C       ATOM   63   C   HIS   A   16   12.856   49.985   −13.768   1.00   44.45   C       ATOM   64   O   HIS   A   16   11.720   50.017   −14.218   1.00   38.53   O       ATOM   65   N   GLU   A   17   13.296   49.033   −12.940   1.00   43.15   N       ATOM   66   CA   GLU   A   17   12.510   47.851   −12.579   1.00   45.72   C       ATOM   67   CB   GLU   A   17   13.325   46.576   −12.794   1.00   46.52   C       ATOM   68   CG   GLU   A   17   13.479   46.141   −14.242   1.00   45.21   C       ATOM   69   CD   GLU   A   17   14.404   44.935   −14.428   1.00   48.39   C       ATOM   70   OE1   GLU   A   17   14.909   44.363   −13.436   1.00   53.51   O       ATOM   71   OE2   GLU   A   17   14.645   44.557   −15.587   1.00   49.07   O       ATOM   72   C   GLU   A   17   12.077   47.943   −11.131   1.00   45.46   C       ATOM   73   O   GLU   A   17   12.914   48.171   −10.252   1.00   47.09   O       ATOM   74   N   GLU   A   18   10.775   47.812   −10.879   1.00   46.25   N       ATOM   75   CA   GLU   A   18   10.287   47.795   −9.500   1.00   47.01   C       ATOM   76   CB   GLU   A   18   9.270   48.907   −9.194   1.00   50.02   C       ATOM   77   CG   GLU   A   18   9.553   49.578   −7.827   1.00   53.61   C       ATOM   78   CD   GLU   A   18   8.322   50.164   −7.143   1.00   58.47   C       ATOM   79   OE1   GLU   A   18   7.339   49.415   −6.922   1.00   58.46   O       ATOM   80   OE2   GLU   A   18   8.356   51.370   −6.792   1.00   52.49   O       ATOM   81   C   GLU   A   18   9.737   46.439   −9.101   1.00   45.25   C       ATOM   82   O   GLU   A   18   8.859   45.885   −9.760   1.00   46.79   O       ATOM   83   N   THR   A   19   10.265   45.937   −7.993   1.00   43.60   N       ATOM   84   CA   THR   A   19   10.022   44.578   −7.547   1.00   40.92   C       ATOM   85   CB   THR   A   19   11.154   44.128   −6.611   1.00   40.82   C       ATOM   86   OG1   THR   A   19   12.355   43.937   −7.372   1.00   46.16   O       ATOM   87   CG2   THR   A   19   10.790   42.835   −5.855   1.00   41.51   C       ATOM   88   C   THR   A   19   8.719   44.532   −6.793   1.00   38.18   C       ATOM   89   O   THR   A   19   8.506   45.332   −5.877   1.00   38.71   O       ATOM   90   N   LEU   A   20   7.869   43.573   −7.155   1.00   35.11   N       ATOM   91   CA   LEU   A   20   6.598   43.341   −6.454   1.00   35.09   C       ATOM   92   CB   LEU   A   20   5.582   42.814   −7.455   1.00   32.21   C       ATOM   93   CG   LEU   A   20   5.228   43.763   −8.593   1.00   42.07   C       ATOM   94   CD1   LEU   A   20   4.775   43.011   −9.829   1.00   41.64   C       ATOM   95   CD2   LEU   A   20   4.192   44.745   −8.158   1.00   31.95   C       ATOM   96   C   LEU   A   20   6.783   42.315   −5.308   1.00   35.93   C       ATOM   97   O   LEU   A   20   6.192   42.424   −4.227   1.00   39.65   O       ATOM   98   N   LEU   A   21   7.647   41.347   −5.560   1.00   37.15   N       ATOM   99   CA   LEU   A   21   7.866   40.212   −4.662   1.00   36.59   C       ATOM   100   CB   LEU   A   21   6.704   39.210   −4.790   1.00   35.23   C       ATOM   101   CG   LEU   A   21   6.824   37.819   −4.076   1.00   30.98   C       ATOM   102   CD1   LEU   A   21   7.141   37.996   −2.622   1.00   42.83   C       ATOM   103   CD2   LEU   A   21   5.549   37.070   −4.163   1.00   31.48   C       ATOM   104   C   LEU   A   21   9.193   39.556   −5.034   1.00   37.39   C       ATOM   105   O   LEU   A   21   9.445   39.256   −6.193   1.00   39.08   O       ATOM   106   N   ASN   A   22   10.053   39.357   −4.050   1.00   39.54   N       ATOM   107   CA   ASN   A   22   11.326   38.676   −4.273   1.00   40.39   C       ATOM   108   CB   ASN   A   22   12.473   39.693   −4.295   1.00   36.59   C       ATOM   109   CG   ASN   A   22   13.795   39.073   −4.663   1.00   42.16   C       ATOM   110   OD1   ASN   A   22   13.963   37.854   −4.578   1.00   37.60   O       ATOM   111   ND2   ASN   A   22   14.759   39.910   −5.068   1.00   32.02   N       ATOM   112   C   ASN   A   22   11.525   37.720   −3.110   1.00   39.65   C       ATOM   113   O   ASN   A   22   11.721   38.195   −1.992   1.00   40.60   O       ATOM   114   N   THR   A   23   11.447   36.403   −3.362   1.00   43.19   N       ATOM   115   CA   THR   A   23   11.631   35.394   −2.304   1.00   39.47   C       ATOM   116   CB   THR   A   23   11.247   33.931   −2.746   1.00   39.83   C       ATOM   117   OG1   THR   A   23   12.103   33.496   −3.803   1.00   29.00   O       ATOM   118   CG2   THR   A   23   9.793   33.845   −3.201   1.00   37.70   C       ATOM   119   C   THR   A   23   13.062   35.354   −1.755   1.00   41.75   C       ATOM   120   O   THR   A   23   13.241   35.056   −0.571   1.00   39.34   O       ATOM   121   N   LYS   A   24   14.058   35.605   −2.613   1.00   42.15   N       ATOM   122   CA   LYS   A   24   15.497   35.577   −2.231   1.00   47.84   C       ATOM   123   CB   LYS   A   24   16.430   35.906   −3.417   1.00   44.41   C       ATOM   124   CG   LYS   A   24   16.713   34.791   −4.408   1.00   36.81   C       ATOM   125   CD   LYS   A   24   17.426   35.348   −5.632   1.00   51.46   C       ATOM   126   CE   LYS   A   24   16.468   36.179   −6.495   1.00   59.42   C       ATOM   127   NZ   LYS   A   24   17.187   37.004   −7.498   1.00   60.14   N       ATOM   128   C   LYS   A   24   15.843   36.550   −1.107   1.00   53.13   C       ATOM   129   O   LYS   A   24   16.809   36.334   −0.372   1.00   57.22   O       ATOM   130   N   LEU   A   25   15.069   37.619   −0.974   1.00   54.53   N       ATOM   131   CA   LEU   A   25   15.320   38.588   0.085   1.00   59.86   C       ATOM   132   CB   LEU   A   25   15.531   40.002   −0.491   1.00   60.08   C       ATOM   133   CG   LEU   A   25   16.786   40.121   −1.390   1.00   60.60   C       ATOM   134   CD1   LEU   A   25   16.740   41.310   −2.344   1.00   63.05   C       ATOM   135   CD2   LEU   A   25   18.090   40.118   −0.596   1.00   66.00   C       ATOM   136   C   LEU   A   25   14.269   38.521   1.205   1.00   62.83   C       ATOM   137   O   LEU   A   25   13.371   39.363   1.295   1.00   65.96   O       ATOM   138   N   GLU   A   26   14.417   37.481   2.034   1.00   63.60   N       ATOM   139   CA   GLU   A   26   13.557   37.151   3.180   1.00   64.36   C       ATOM   140   CB   GLU   A   26   12.164   36.740   2.703   1.00   65.26   C       ATOM   141   CG   GLU   A   26   11.181   36.462   3.840   1.00   68.35   C       ATOM   142   CD   GLU   A   26   10.195   35.365   3.503   1.00   69.03   C       ATOM   143   OE1   GLU   A   26   10.611   34.373   2.866   1.00   72.16   O       ATOM   144   OE2   GLU   A   26   9.006   35.483   3.885   1.00   70.04   O       ATOM   145   C   GLU   A   26   14.182   35.967   3.926   1.00   62.58   C       ATOM   146   O   GLU   A   26   14.503   34.958   3.303   1.00   61.58   O       ATOM   147   N   THR   A   27   14.358   36.078   5.244   1.00   62.75   N       ATOM   148   CA   THR   A   27   14.928   34.965   6.031   1.00   62.27   C       ATOM   149   CB   THR   A   27   16.365   35.278   6.593   1.00   62.72   C       ATOM   150   OG1   THR   A   27   17.247   35.654   5.526   1.00   60.03   O       ATOM   151   CG2   THR   A   27   16.959   34.054   7.245   1.00   56.16   C       ATOM   152   C   THR   A   27   13.979   34.389   7.117   1.00   62.81   C       ATOM   153   O   THR   A   27   14.427   33.864   8.148   1.00   63.93   O       ATOM   154   N   ALA   A   28   12.673   34.504   6.868   1.00   62.26   N       ATOM   155   CA   ALA   A   28   11.630   33.803   7.634   1.00   60.61   C       ATOM   156   CB   ALA   A   28   10.916   34.758   8.558   1.00   62.26   C       ATOM   157   C   ALA   A   28   10.646   33.186   6.647   1.00   58.58   C       ATOM   158   O   ALA   A   28   10.582   33.623   5.516   1.00   61.77   O       ATOM   159   N   ASP   A   29   9.867   32.197   7.080   1.00   57.43   N       ATOM   160   CA   ASP   A   29   9.059   31.336   6.188   1.00   51.76   C       ATOM   161   CB   ASP   A   29   8.248   30.372   7.029   1.00   52.60   C       ATOM   162   CG   ASP   A   29   9.024   29.852   8.206   1.00   54.73   C       ATOM   163   OD1   ASP   A   29   9.472   28.696   8.133   1.00   65.52   O       ATOM   164   OD2   ASP   A   29   9.221   30.597   9.195   1.00   57.50   O       ATOM   165   C   ASP   A   29   8.133   32.114   5.268   1.00   48.96   C       ATOM   166   O   ASP   A   29   7.583   33.121   5.686   1.00   50.09   O       ATOM   167   N   LEU   A   30   7.954   31.637   4.027   1.00   44.57   N       ATOM   168   CA   LEU   A   30   7.173   32.357   2.999   1.00   38.90   C       ATOM   169   CB   LEU   A   30   7.469   31.824   1.593   1.00   33.40   C       ATOM   170   CG   LEU   A   30   8.847   32.055   0.993   1.00   31.55   C       ATOM   171   CD1   LEU   A   30   9.081   30.975   −0.047   1.00   34.59   C       ATOM   172   CD2   LEU   A   30   8.873   33.455   0.382   1.00   35.00   C       ATOM   173   C   LEU   A   30   5.692   32.186   3.288   1.00   37.96   C       ATOM   174   O   LEU   A   30   4.886   33.060   2.968   1.00   38.81   O       ATOM   175   N   LYS   A   31   5.352   31.042   3.872   1.00   36.60   N       ATOM   176   CA   LYS   A   31   3.986   30.689   4.309   1.00   36.65   C       ATOM   177   CB   LYS   A   31   3.524   31.555   5.506   1.00   38.57   C       ATOM   178   CG   LYS   A   31   4.378   31.527   6.791   1.00   46.53   C       ATOM   179   CD   LYS   A   31   4.249   30.238   7.593   1.00   57.30   C       ATOM   180   CE   LYS   A   31   4.170   30.493   9.118   1.00   60.83   C       ATOM   181   NZ   LYS   A   31   5.181   31.459   9.679   1.00   65.93   N       ATOM   182   C   LYS   A   31   2.977   30.782   3.181   1.00   39.42   C       ATOM   183   O   LYS   A   31   1.858   31.305   3.381   1.00   41.43   O       ATOM   184   N   TRP   A   32   3.371   30.358   1.973   1.00   35.13   N       ATOM   185   CA   TRP   A   32   2.453   30.416   0.834   1.00   33.15   C       ATOM   186   CB   TRP   A   32   3.161   30.207   −0.500   1.00   28.95   C       ATOM   187   CG   TRP   A   32   4.039   31.317   −0.919   1.00   34.75   C       ATOM   188   CD1   TRP   A   32   4.205   32.537   −0.312   1.00   33.11   C       ATOM   189   NE1   TRP   A   32   5.093   33.291   −1.021   1.00   29.19   N       ATOM   190   CE2   TRP   A   32   5.511   32.583   −2.117   1.00   31.35   C       ATOM   191   CD2   TRP   A   32   4.872   31.332   −2.081   1.00   32.07   C       ATOM   192   CE3   TRP   A   32   5.140   30.397   −3.090   1.00   28.33   C       ATOM   193   CZ3   TRP   A   32   6.044   30.747   −4.096   1.00   29.85   C       ATOM   194   CH2   TRP   A   32   6.681   32.008   −4.088   1.00   33.09   C       ATOM   195   CZ2   TRP   A   32   6.443   32.928   −3.108   1.00   29.70   C       ATOM   196   C   TRP   A   32   1.381   29.360   1.045   1.00   34.03   C       ATOM   197   O   TRP   A   32   1.475   28.597   1.979   1.00   31.83   O       ATOM   198   N   VAL   A   33   0.387   29.316   0.166   1.00   36.83   N       ATOM   199   CA   VAL   A   33   −0.813   28.472   0.377   1.00   34.51   C       ATOM   200   CB   VAL   A   33   −2.075   29.329   0.158   1.00   39.47   C       ATOM   201   CG1   VAL   A   33   −3.367   28.480   0.048   1.00   38.42   C       ATOM   202   CG2   VAL   A   33   −2.180   30.345   1.283   1.00   29.62   C       ATOM   203   C   VAL   A   33   −0.811   27.254   −0.516   1.00   35.90   C       ATOM   204   O   VAL   A   33   −0.618   27.372   −1.721   1.00   35.14   O       ATOM   205   N   THR   A   34   −1.031   26.075   0.077   1.00   36.36   N       ATOM   206   CA   THR   A   34   −1.112   24.856   −0.726   1.00   36.51   C       ATOM   207   CB   THR   A   34   −0.110   23.848   −0.259   1.00   29.05   C       ATOM   208   OG1   THR   A   34   −0.276   23.679   1.146   1.00   30.25   O       ATOM   209   CG2   THR   A   34   1.324   24.336   −0.559   1.00   36.15   C       ATOM   210   C   THR   A   34   −2.504   24.202   −0.691   1.00   36.01   C       ATOM   211   O   THR   A   34   −3.244   24.330   0.293   1.00   39.89   O       ATOM   212   N   PHE   A   35   −2.836   23.508   −1.777   1.00   40.71   N       ATOM   213   CA   PHE   A   35   −4.038   22.661   −1.865   1.00   37.31   C       ATOM   214   CB   PHE   A   35   −5.242   23.488   −2.352   1.00   39.56   C       ATOM   215   CG   PHE   A   35   −6.458   22.656   −2.745   1.00   31.37   C       ATOM   216   CD1   PHE   A   35   −7.425   22.323   −1.800   1.00   38.00   C       ATOM   217   CE1   PHE   A   35   −8.536   21.564   −2.155   1.00   34.26   C       ATOM   218   CZ   PHE   A   35   −8.710   21.162   −3.467   1.00   41.72   C       ATOM   219   CE2   PHE   A   35   −7.770   21.507   −4.424   1.00   38.74   C       ATOM   220   CD2   PHE   A   35   −6.652   22.255   −4.061   1.00   37.81   C       ATOM   221   C   PHE   A   35   −3.799   21.477   −2.807   1.00   38.54   C       ATOM   222   O   PHE   A   35   −3.222   21.649   −3.876   1.00   41.98   O       ATOM   223   N   PRO   A   36   −4.272   20.275   −2.435   1.00   36.71   N       ATOM   224   CA   PRO   A   36   −4.947   19.954   −1.169   1.00   37.64   C       ATOM   225   CB   PRO   A   36   −5.768   18.692   −1.504   1.00   39.48   C       ATOM   226   CG   PRO   A   36   −5.523   18.410   −2.972   1.00   38.36   C       ATOM   227   CD   PRO   A   36   −4.236   19.098   −3.318   1.00   40.07   C       ATOM   228   C   PRO   A   36   −3.904   19.700   −0.087   1.00   40.22   C       ATOM   229   O   PRO   A   36   −2.750   19.379   −0.420   1.00   41.14   O       ATOM   230   N   GLN   A   37   −4.267   19.883   1.186   1.00   36.93   N       ATOM   231   CA   GLN   A   37   −3.271   19.770   2.261   1.00   39.87   C       ATOM   232   CB   GLN   A   37   −3.542   20.763   3.406   1.00   40.23   C       ATOM   233   CG   GLN   A   37   −2.965   22.128   3.109   1.00   42.03   C       ATOM   234   CD   GLN   A   37   −3.673   23.293   3.765   1.00   44.82   C       ATOM   235   OE1   GLN   A   37   −4.184   23.192   4.876   1.00   50.61   O       ATOM   236   NE2   GLN   A   37   −3.697   24.422   3.068   1.00   47.44   N       ATOM   237   C   GLN   A   37   −3.103   18.329   2.732   1.00   41.85   C       ATOM   238   O   GLN   A   37   −3.605   17.935   3.802   1.00   43.80   O       ATOM   239   N   VAL   A   38   −2.413   17.550   1.889   1.00   40.81   N       ATOM   240   CA   VAL   A   38   −2.108   16.133   2.121   1.00   40.56   C       ATOM   241   CB   VAL   A   38   −2.824   15.199   1.098   1.00   44.60   C       ATOM   242   CG1   VAL   A   38   −4.312   15.348   1.189   1.00   41.50   C       ATOM   243   CG2   VAL   A   38   −2.366   15.498   −0.335   1.00   46.63   C       ATOM   244   C   VAL   A   38   −0.623   15.866   1.983   1.00   40.11   C       ATOM   245   O   VAL   A   38   0.122   16.692   1.460   1.00   33.72   O       ATOM   246   N   ASP   A   39   −0.191   14.686   2.413   1.00   39.32   N       ATOM   247   CA   ASP   A   39   1.187   14.302   2.188   1.00   39.86   C       ATOM   248   CB   ASP   A   39   1.489   12.950   2.845   1.00   42.53   C       ATOM   249   CG   ASP   A   39   2.889   12.892   3.446   1.00   54.40   C       ATOM   250   OD1   ASP   A   39   3.849   13.397   2.806   1.00   56.20   O       ATOM   251   OD2   ASP   A   39   3.032   12.338   4.564   1.00   62.34   O       ATOM   252   C   ASP   A   39   1.494   14.312   0.682   1.00   38.22   C       ATOM   253   O   ASP   A   39   0.734   13.790   −0.121   1.00   39.89   O       ATOM   254   N   GLY   A   40   2.598   14.938   0.294   1.00   36.82   N       ATOM   255   CA   GLY   A   40   2.906   15.094   −1.115   1.00   36.32   C       ATOM   256   C   GLY   A   40   2.726   16.504   −1.637   1.00   36.89   C       ATOM   257   O   GLY   A   40   3.230   16.826   −2.713   1.00   40.19   O       ATOM   258   N   GLN   A   41   1.959   17.320   −0.910   1.00   34.90   N       ATOM   259   CA   GLN   A   41   1.794   18.743   −1.202   1.00   31.38   C       ATOM   260   CB   GLN   A   41   0.938   19.401   −0.098   1.00   34.79   C       ATOM   261   CG   GLN   A   41   1.706   19.597   1.237   1.00   31.27   C       ATOM   262   CD   GLN   A   41   0.855   19.958   2.420   1.00   32.64   C       ATOM   263   OE1   GLN   A   41   0.175   20.974   2.428   1.00   37.65   O       ATOM   264   NE2   GLN   A   41   0.921   19.135   3.456   1.00   36.27   N       ATOM   265   C   GLN   A   41   3.165   19.451   −1.292   1.00   32.83   C       ATOM   266   O   GLN   A   41   4.113   19.037   −0.633   1.00   30.94   O       ATOM   267   N   TRP   A   42   3.246   20.579   −2.015   1.00   27.39   N       ATOM   268   CA   TRP   A   42   4.499   21.331   −2.053   1.00   30.30   C       ATOM   269   CB   TRP   A   42   4.362   22.691   −2.791   1.00   30.12   C       ATOM   270   CG   TRP   A   42   4.056   22.655   −4.294   1.00   24.67   C       ATOM   271   CD1   TRP   A   42   2.866   22.342   −4.887   1.00   29.46   C       ATOM   272   NE1   TRP   A   42   2.993   22.421   −6.268   1.00   26.03   N       ATOM   273   CE2   TRP   A   42   4.270   22.836   −6.574   1.00   26.75   C       ATOM   274   CD2   TRP   A   42   4.969   22.988   −5.367   1.00   22.65   C       ATOM   275   CE3   TRP   A   42   6.310   23.374   −5.402   1.00   35.38   C       ATOM   276   CZ3   TRP   A   42   6.902   23.641   −6.633   1.00   25.44   C       ATOM   277   CH2   TRP   A   42   6.173   23.493   −7.821   1.00   33.53   C       ATOM   278   CZ2   TRP   A   42   4.838   23.106   −7.808   1.00   26.55   C       ATOM   279   C   TRP   A   42   4.829   21.626   −0.614   1.00   25.05   C       ATOM   280   O   TRP   A   42   3.940   21.655   0.198   1.00   26.88   O       ATOM   281   N   GLU   A   43   6.102   21.934   −0.351   1.00   28.52   N       ATOM   282   CA   GLU   A   43   6.648   22.065   0.960   1.00   28.30   C       ATOM   283   CB   GLU   A   43   7.221   20.708   1.368   0.50   29.79   C       ATOM   284   CG   GLU   A   43   7.855   20.711   2.685   0.50   27.80   C       ATOM   285   CD   GLU   A   43   7.621   19.437   3.393   0.50   29.66   C       ATOM   286   OE1   GLU   A   43   7.052   19.510   4.485   0.50   28.25   O       ATOM   287   OE2   GLU   A   43   7.976   18.362   2.850   0.50   33.51   O       ATOM   288   C   GLU   A   43   7.764   23.091   0.953   1.00   29.96   C       ATOM   289   O   GLU   A   43   8.672   23.045   0.108   1.00   30.23   O       ATOM   290   N   GLU   A   44   7.694   23.981   1.942   1.00   28.74   N       ATOM   291   CA   GLU   A   44   8.696   24.984   2.273   1.00   32.50   C       ATOM   292   CB   GLU   A   44   7.990   26.178   2.925   1.00   29.06   C       ATOM   293   CG   GLU   A   44   8.921   27.058   3.729   1.00   42.19   C       ATOM   294   CD   GLU   A   44   8.514   28.502   3.654   1.00   35.09   C       ATOM   295   OE1   GLU   A   44   7.329   28.813   3.928   1.00   45.10   O       ATOM   296   OE2   GLU   A   44   9.387   29.325   3.332   1.00   44.69   O       ATOM   297   C   GLU   A   44   9.898   24.539   3.154   1.00   27.75   C       ATOM   298   O   GLU   A   44   9.733   23.944   4.232   1.00   33.26   O       ATOM   299   N   LEU   A   45   11.102   24.921   2.734   1.00   28.38   N       ATOM   300   CA   LEU   A   45   12.330   24.400   3.255   1.00   33.31   C       ATOM   301   CB   LEU   A   45   12.556   23.055   2.501   1.00   37.82   C       ATOM   302   CG   LEU   A   45   13.623   21.985   2.685   1.00   45.75   C       ATOM   303   CD1   LEU   A   45   13.124   20.793   1.949   1.00   39.39   C       ATOM   304   CD2   LEU   A   45   14.894   22.391   2.058   1.00   47.39   C       ATOM   305   C   LEU   A   45   13.422   25.417   2.902   1.00   32.67   C       ATOM   306   O   LEU   A   45   13.383   26.031   1.850   1.00   31.80   O       ATOM   307   N   SER   A   46   14.375   25.625   3.804   0.50   25.99   N       ATOM   308   CA   SER   A   46   15.545   26.385   3.455   0.50   25.69   C       ATOM   309   CB   SER   A   46   16.319   26.790   4.722   0.50   21.08   C       ATOM   310   OG   SER   A   46   15.673   27.845   5.444   0.50   17.40   O       ATOM   311   C   SER   A   46   16.411   25.501   2.538   0.50   25.37   C       ATOM   312   O   SER   A   46   16.470   24.281   2.688   0.50   27.19   O       ATOM   313   N   GLY   A   47   17.042   26.131   1.567   1.00   35.25   N       ATOM   314   CA   GLY   A   47   18.069   25.515   0.770   1.00   37.20   C       ATOM   315   C   GLY   A   47   19.112   26.509   0.272   1.00   40.71   C       ATOM   316   O   GLY   A   47   19.031   27.723   0.479   1.00   37.07   O       ATOM   317   N   LEU   A   48   20.083   25.974   −0.444   1.00   42.16   N       ATOM   318   CA   LEU   A   48   21.090   26.788   −1.071   1.00   46.36   C       ATOM   319   CB   LEU   A   48   22.472   26.147   −0.882   1.00   47.59   C       ATOM   320   CG   LEU   A   48   23.420   26.858   0.095   1.00   46.13   C       ATOM   321   CD1   LEU   A   48   22.890   26.860   1.523   1.00   40.81   C       ATOM   322   CD2   LEU   A   48   24.840   26.268   0.015   1.00   45.26   C       ATOM   323   C   LEU   A   48   20.769   26.947   −2.526   1.00   47.20   C       ATOM   324   O   LEU   A   48   20.149   26.061   −3.134   1.00   47.47   O       ATOM   325   N   ASP   A   49   21.135   28.103   −3.069   1.00   48.27   N       ATOM   326   CA   ASP   A   49   21.056   28.332   −4.499   1.00   51.38   C       ATOM   327   CB   ASP   A   49   20.188   29.567   −4.845   1.00   50.70   C       ATOM   328   CG   ASP   A   49   20.680   30.869   −4.195   1.00   53.56   C       ATOM   329   OD1   ASP   A   49   21.425   30.828   −3.196   1.00   53.57   O       ATOM   330   OD2   ASP   A   49   20.299   31.962   −4.694   1.00   58.12   O       ATOM   331   C   ASP   A   49   22.474   28.435   −5.069   1.00   52.11   C       ATOM   332   O   ASP   A   49   23.446   28.314   −4.329   1.00   53.92   O       ATOM   333   N   GLU   A   50   22.576   28.657   −6.375   1.00   54.51   N       ATOM   334   CA   GLU   A   50   23.860   28.606   −7.063   1.00   56.83   C       ATOM   335   CB   GLU   A   50   23.663   28.272   −8.543   1.00   57.48   C       ATOM   336   CG   GLU   A   50   24.955   28.198   −9.341   1.00   58.63   C       ATOM   337   CD   GLU   A   50   24.747   28.485   −10.815   1.00   63.28   C       ATOM   338   OE1   GLU   A   50   23.826   29.261   −11.147   1.00   62.81   O       ATOM   339   OE2   GLU   A   50   25.505   27.935   −11.641   1.00   64.02   O       ATOM   340   C   GLU   A   50   24.615   29.924   −6.920   1.00   58.52   C       ATOM   341   O   GLU   A   50   25.752   30.052   −7.375   1.00   58.64   O       ATOM   342   N   GLU   A   51   24.016   30.884   −6.229   1.00   60.08   N       ATOM   343   CA   GLU   A   51   24.755   32.014   −5.680   1.00   61.33   C       ATOM   344   CB   GLU   A   51   23.862   33.246   −5.596   1.00   60.98   C       ATOM   345   CG   GLU   A   51   24.093   34.229   −6.720   1.00   65.33   C       ATOM   346   CD   GLU   A   51   25.552   34.338   −7.099   1.00   66.61   C       ATOM   347   OE1   GLU   A   51   26.153   33.321   −7.491   1.00   63.39   O       ATOM   348   OE2   GLU   A   51   26.100   35.448   −7.000   1.00   70.97   O       ATOM   349   C   GLU   A   51   25.355   31.726   −4.313   1.00   60.91   C       ATOM   350   O   GLU   A   51   26.225   32.444   −3.835   1.00   59.55   O       ATOM   351   N   GLN   A   52   24.893   30.666   −3.681   1.00   60.48   N       ATOM   352   CA   GLN   A   52   25.602   30.174   −2.532   1.00   60.49   C       ATOM   353   CB   GLN   A   52   25.917   28.705   −2.692   1.00   61.75   C       ATOM   354   C   GLN   A   52   24.854   30.424   −1.242   1.00   59.29   C       ATOM   355   O   GLN   A   52   25.237   29.908   −0.197   1.00   60.10   O       ATOM   356   N   HIS   A   53   23.804   31.235   −1.297   1.00   56.75   N       ATOM   357   CA   HIS   A   53   23.253   31.737   −0.044   1.00   54.55   C       ATOM   358   CB   HIS   A   53   23.006   33.245   −0.134   1.00   52.15   C       ATOM   359   CG   HIS   A   53   24.232   34.039   −0.458   1.00   59.55   C       ATOM   360   ND1   HIS   A   53   24.213   35.409   −0.608   1.00   58.63   N       ATOM   361   CE1   HIS   A   53   25.431   35.837   −0.890   1.00   60.64   C       ATOM   362   NE2   HIS   A   53   26.239   34.793   −0.929   1.00   65.96   N       ATOM   363   CD2   HIS   A   53   25.515   33.657   −0.662   1.00   62.27   C       ATOM   364   C   HIS   A   53   21.959   31.015   0.317   1.00   52.31   C       ATOM   365   O   HIS   A   53   21.175   30.649   −0.558   1.00   50.31   O       ATOM   366   N   SER   A   54   21.743   30.812   1.613   1.00   50.47   N       ATOM   367   CA   SER   A   54   20.530   30.169   2.094   1.00   47.56   C       ATOM   368   CB   SER   A   54   20.596   29.927   3.613   1.00   48.43   C       ATOM   369   OG   SER   A   54   19.286   29.843   4.172   1.00   45.67   O       ATOM   370   C   SER   A   54   19.287   30.986   1.758   1.00   45.87   C       ATOM   371   O   SER   A   54   19.123   32.128   2.237   1.00   48.05   O       ATOM   372   N   VAL   A   55   18.402   30.407   0.953   1.00   40.45   N       ATOM   373   CA   VAL   A   55   17.105   31.085   0.673   1.00   39.01   C       ATOM   374   CB   VAL   A   55   17.015   31.617   −0.788   1.00   36.82   C       ATOM   375   CG1   VAL   A   55   17.864   32.882   −0.951   1.00   44.80   C       ATOM   376   CG2   VAL   A   55   17.440   30.537   −1.781   1.00   37.51   C       ATOM   377   C   VAL   A   55   15.919   30.179   1.016   1.00   34.20   C       ATOM   378   O   VAL   A   55   16.091   28.989   1.260   1.00   37.43   O       ATOM   379   N   ARG   A   56   14.731   30.761   1.043   1.00   31.69   N       ATOM   380   CA   ARG   A   56   13.461   30.033   1.228   1.00   34.24   C       ATOM   381   CB   ARG   A   56   12.380   31.019   1.670   1.00   34.51   C       ATOM   382   CG   ARG   A   56   12.499   31.406   3.120   1.00   40.35   C       ATOM   383   CD   ARG   A   56   11.870   30.286   3.920   1.00   42.68   C       ATOM   384   NE   ARG   A   56   12.569   30.118   5.162   1.00   54.07   N       ATOM   385   CZ   ARG   A   56   12.264   29.246   6.110   1.00   45.17   C       ATOM   386   NH1   ARG   A   56   11.208   28.431   6.026   1.00   32.64   N       ATOM   387   NH2   ARG   A   56   13.020   29.249   7.184   1.00   43.41   N       ATOM   388   C   ARG   A   56   13.050   29.358   −0.068   1.00   36.72   C       ATOM   389   O   ARG   A   56   12.933   30.049   −1.074   1.00   37.99   O       ATOM   390   N   THR   A   57   12.898   28.028   −0.054   1.00   37.40   N       ATOM   391   CA   THR   A   57   12.555   27.264   −1.269   1.00   36.12   C       ATOM   392   CB   THR   A   57   13.657   26.239   −1.669   1.00   31.88   C       ATOM   393   OG1   THR   A   57   13.665   25.129   −0.746   1.00   32.23   O       ATOM   394   CG2   THR   A   57   15.055   26.937   −1.774   1.00   30.55   C       ATOM   395   C   THR   A   57   11.198   26.536   −1.150   1.00   30.38   C       ATOM   396   O   THR   A   57   10.690   26.366   −0.049   1.00   32.87   O       ATOM   397   N   TYR   A   58   10.671   26.073   −2.281   1.00   29.60   N       ATOM   398   CA   TYR   A   58   9.463   25.211   −2.336   1.00   25.84   C       ATOM   399   CB   TYR   A   58   8.204   25.927   −2.875   1.00   33.81   C       ATOM   400   CG   TYR   A   58   7.373   26.568   −1.769   1.00   32.75   C       ATOM   401   CD1   TYR   A   58   6.581   25.762   −0.919   1.00   36.07   C       ATOM   402   CE1   TYR   A   58   5.857   26.309   0.107   1.00   33.85   C       ATOM   403   CZ   TYR   A   58   5.909   27.681   0.318   1.00   28.13   C       ATOM   404   OH   TYR   A   58   5.143   28.196   1.340   1.00   39.16   O       ATOM   405   CE2   TYR   A   58   6.675   28.495   −0.494   1.00   32.86   C       ATOM   406   CD2   TYR   A   58   7.385   27.940   −1.549   1.00   30.61   C       ATOM   407   C   TYR   A   58   9.759   23.931   −3.119   1.00   27.75   C       ATOM   408   O   TYR   A   58   10.237   23.944   −4.251   1.00   30.30   O       ATOM   409   N   GLU   A   59   9.493   22.808   −2.518   1.00   26.84   N       ATOM   410   CA   GLU   A   59   9.743   21.517   −3.207   1.00   28.50   C       ATOM   411   CB   GLU   A   59   10.734   20.698   −2.395   1.00   25.37   C       ATOM   412   CG   GLU   A   59   12.194   21.194   −2.554   1.00   32.71   C       ATOM   413   CD   GLU   A   59   13.169   20.434   −1.708   1.00   35.65   C       ATOM   414   OE1   GLU   A   59   12.752   19.458   −1.043   1.00   42.68   O       ATOM   415   OE2   GLU   A   59   14.373   20.788   −1.734   1.00   38.99   O       ATOM   416   C   GLU   A   59   8.445   20.719   −3.429   1.00   29.63   C       ATOM   417   O   GLU   A   59   7.573   20.699   −2.581   1.00   29.86   O       ATOM   418   N   VAL   A   60   8.304   20.114   −4.597   1.00   32.15   N       ATOM   419   CA   VAL   A   60   7.342   19.043   −4.786   1.00   28.58   C       ATOM   420   CB   VAL   A   60   6.074   19.527   −5.482   1.00   30.98   C       ATOM   421   CG1   VAL   A   60   6.353   19.831   −6.910   1.00   23.51   C       ATOM   422   CG2   VAL   A   60   4.903   18.501   −5.270   1.00   28.38   C       ATOM   423   C   VAL   A   60   8.023   17.825   −5.495   1.00   32.59   C       ATOM   424   O   VAL   A   60   8.836   17.970   −6.418   1.00   31.84   O       ATOM   425   N   CYS   A   61   7.706   16.628   −5.036   1.00   32.96   N       ATOM   426   CA   CYS   A   61   8.172   15.412   −5.731   1.00   35.72   C       ATOM   427   CB   CYS   A   61   9.667   15.181   −5.499   1.00   36.99   C       ATOM   428   SG   CYS   A   61   10.357   13.789   −6.460   1.00   35.75   S       ATOM   429   C   CYS   A   61   7.320   14.168   −5.440   1.00   39.90   C       ATOM   430   O   CYS   A   61   7.784   13.212   −4.847   1.00   37.78   O       ATOM   431   N   ASP   A   62   6.070   14.192   −5.902   1.00   42.20   N       ATOM   432   CA   ASP   A   62   5.098   13.145   −5.583   1.00   46.74   C       ATOM   433   CB   ASP   A   62   3.882   13.839   −4.937   1.00   44.78   C       ATOM   434   CG   ASP   A   62   2.847   12.878   −4.360   1.00   47.88   C       ATOM   435   OD1   ASP   A   62   3.210   11.852   −3.750   1.00   41.91   O       ATOM   436   OD2   ASP   A   62   1.648   13.198   −4.502   1.00   40.24   O       ATOM   437   C   ASP   A   62   4.748   12.325   −6.856   1.00   50.85   C       ATOM   438   O   ASP   A   62   3.567   12.170   −7.223   1.00   49.30   O       ATOM   439   N   VAL   A   63   5.792   11.771   −7.494   1.00   51.88   N       ATOM   440   CA   VAL   A   63   5.747   11.308   −8.913   1.00   54.74   C       ATOM   441   CB   VAL   A   63   7.166   11.296   −9.566   1.00   54.31   C       ATOM   442   CG1   VAL   A   63   7.692   12.700   −9.757   1.00   51.43   C       ATOM   443   CG2   VAL   A   63   8.139   10.455   −8.736   1.00   54.86   C       ATOM   444   C   VAL   A   63   5.123   9.933   −9.169   1.00   59.46   C       ATOM   445   O   VAL   A   63   4.803   9.596   −10.319   1.00   59.09   O       ATOM   446   N   GLN   A   64   4.992   9.134   −8.108   1.00   62.97   N       ATOM   447   CA   GLN   A   64   4.441   7.787   −8.205   1.00   67.89   C       ATOM   448   CB   GLN   A   64   5.523   6.735   −7.964   1.00   69.08   C       ATOM   449   C   GLN   A   64   3.331   7.600   −7.193   1.00   70.54   C       ATOM   450   O   GLN   A   64   2.381   6.841   −7.433   1.00   71.49   O       ATOM   451   N   ARG   A   65   3.469   8.300   −6.065   1.00   72.75   N       ATOM   452   CA   ARG   A   65   2.538   8.217   −4.937   1.00   73.43   C       ATOM   453   CB   ARG   A   65   3.107   8.979   −3.739   1.00   73.53   C       ATOM   454   CG   ARG   A   65   4.643   8.994   −3.671   1.00   74.34   C       ATOM   455   CD   ARG   A   65   5.151   9.895   −2.553   1.00   74.16   C       ATOM   456   NE   ARG   A   65   6.539   9.612   −2.185   1.00   78.12   N       ATOM   457   CZ   ARG   A   65   6.912   8.709   −1.276   1.00   81.38   C       ATOM   458   NH1   ARG   A   65   8.203   8.535   −1.008   1.00   81.84   N       ATOM   459   NH2   ARG   A   65   6.001   7.979   −0.630   1.00   80.28   N       ATOM   460   C   ARG   A   65   1.175   8.781   −5.319   1.00   74.40   C       ATOM   461   O   ARG   A   65   0.137   8.308   −4.848   1.00   75.23   O       ATOM   462   N   ALA   A   66   1.187   9.752   −6.221   1.00   75.02   N       ATOM   463   CA   ALA   A   66   −0.022   10.410   −6.687   1.00   75.51   C       ATOM   464   CB   ALA   A   66   0.324   11.758   −7.268   1.00   74.75   C       ATOM   465   C   ALA   A   66   −0.772   9.571   −7.719   1.00   76.66   C       ATOM   466   O   ALA   A   66   −0.182   8.738   −8.406   1.00   75.96   O       ATOM   467   N   PRO   A   67   −2.081   9.805   −7.831   1.00   76.02   N       ATOM   468   CA   PRO   A   67   −2.860   9.213   −8.920   1.00   76.11   C       ATOM   469   CB   PRO   A   67   −3.444   7.964   −8.264   1.00   76.99   C       ATOM   470   CG   PRO   A   67   −3.465   8.286   −6.762   1.00   76.64   C       ATOM   471   CD   PRO   A   67   −2.737   9.576   −6.533   1.00   75.96   C       ATOM   472   C   PRO   A   67   −4.001   10.095   −9.427   1.00   73.84   C       ATOM   473   O   PRO   A   67   −5.117   9.990   −8.927   1.00   74.12   O       ATOM   474   N   GLY   A   68   −3.731   10.931   −10.422   1.00   71.47   N       ATOM   475   CA   GLY   A   68   −4.781   11.685   −11.088   1.00   68.41   C       ATOM   476   C   GLY   A   68   −4.893   13.125   −10.618   1.00   65.77   C       ATOM   477   O   GLY   A   68   −5.894   13.791   −10.859   1.00   65.68   O       ATOM   478   N   GLN   A   69   −3.854   13.607   −9.946   1.00   62.00   N       ATOM   479   CA   GLN   A   69   −4.019   14.608   −8.911   1.00   58.03   C       ATOM   480   CB   GLN   A   69   −3.807   13.999   −7.541   1.00   57.70   C       ATOM   481   CG   GLN   A   69   −4.617   14.674   −6.473   1.00   60.32   C       ATOM   482   CD   GLN   A   69   −3.768   15.263   −5.391   1.00   63.50   C       ATOM   483   OE1   GLN   A   69   −2.571   15.035   −5.343   1.00   69.20   O       ATOM   484   NE2   GLN   A   69   −4.383   16.027   −4.509   1.00   64.13   N       ATOM   485   C   GLN   A   69   −3.103   15.810   −9.075   1.00   54.71   C       ATOM   486   O   GLN   A   69   −2.022   15.710   −9.640   1.00   52.38   O       ATOM   487   N   ALA   A   70   −3.554   16.948   −8.567   1.00   50.26   N       ATOM   488   CA   ALA   A   70   −2.866   18.217   −8.769   1.00   45.28   C       ATOM   489   CB   ALA   A   70   −3.709   19.146   −9.653   1.00   46.12   C       ATOM   490   C   ALA   A   70   −2.513   18.911   −7.461   1.00   40.85   C       ATOM   491   O   ALA   A   70   −3.392   19.227   −6.667   1.00   40.28   O       ATOM   492   N   HIS   A   71   −1.226   19.190   −7.258   1.00   38.57   N       ATOM   493   CA   HIS   A   71   −0.776   19.932   −6.072   1.00   34.83   C       ATOM   494   CB   HIS   A   71   0.567   19.415   −5.531   1.00   33.42   C       ATOM   495   CG   HIS   A   71   0.567   17.965   −5.101   1.00   36.67   C       ATOM   496   ND1   HIS   A   71   −0.248   17.483   −4.094   1.00   42.49   N       ATOM   497   CE1   HIS   A   71   −0.032   16.189   −3.928   1.00   37.72   C       ATOM   498   NE2   HIS   A   71   0.924   15.816   −4.764   1.00   35.72   N       ATOM   499   CD2   HIS   A   71   1.314   16.912   −5.507   1.00   40.69   C       ATOM   500   C   HIS   A   71   −0.633   21.421   −6.445   1.00   36.72   C       ATOM   501   O   HIS   A   71   0.255   21.811   −7.240   1.00   30.07   O       ATOM   502   N   TRP   A   72   −1.458   22.244   −5.819   1.00   35.14   N       ATOM   503   CA   TRP   A   72   −1.437   23.690   −6.072   1.00   34.04   C       ATOM   504   CB   TRP   A   72   −2.853   24.250   −6.076   1.00   35.63   C       ATOM   505   CG   TRP   A   72   −3.670   23.874   −7.269   1.00   30.19   C       ATOM   506   CD1   TRP   A   72   −4.373   22.721   −7.443   1.00   37.72   C       ATOM   507   NE1   TRP   A   72   −4.994   22.715   −8.654   1.00   37.02   N       ATOM   508   CE2   TRP   A   72   −4.722   23.892   −9.300   1.00   41.37   C       ATOM   509   CD2   TRP   A   72   −3.877   24.648   −8.455   1.00   43.82   C       ATOM   510   CE3   TRP   A   72   −3.443   25.912   −8.885   1.00   41.53   C       ATOM   511   CZ3   TRP   A   72   −3.857   26.370   −10.124   1.00   37.00   C       ATOM   512   CH2   TRP   A   72   −4.701   25.594   −10.945   1.00   37.71   C       ATOM   513   CZ2   TRP   A   72   −5.139   24.352   −10.549   1.00   45.05   C       ATOM   514   C   TRP   A   72   −0.591   24.390   −5.020   1.00   32.97   C       ATOM   515   O   TRP   A   72   −0.574   23.956   −3.862   1.00   30.07   C       ATOM   516   N   LEU   A   73   0.198   25.379   −5.463   1.00   29.15   N       ATOM   517   CA   LEU   A   73   0.924   26.326   −4.587   1.00   28.01   C       ATOM   518   CB   LEU   A   73   2.450   26.140   −4.720   1.00   24.79   C       ATOM   519   CG   LEU   A   73   3.354   27.007   −3.870   1.00   28.60   C       ATOM   520   CD1   LEU   A   73   3.116   26.818   −2.389   1.00   28.15   C       ATOM   521   CD2   LEU   A   73   4.848   26.781   −4.220   1.00   30.48   C       ATOM   522   C   LEU   A   73   0.587   27.771   −4.989   1.00   28.82   C       ATOM   523   O   LEU   A   73   0.741   28.143   −6.166   1.00   32.47   O       ATOM   524   N   ARG   A   74   0.229   28.601   −4.016   1.00   26.25   N       ATOM   525   CA   ARG   A   74   −0.171   29.997   −4.349   1.00   31.34   C       ATOM   526   CB   ARG   A   74   −1.692   30.180   −4.242   1.00   32.48   C       ATOM   527   CG   ARG   A   74   −2.258   31.453   −4.942   1.00   30.02   C       ATOM   528   CD   ARG   A   74   −3.720   31.633   −4.574   1.00   36.24   C       ATOM   529   NE   ARG   A   74   −3.803   31.821   −3.132   1.00   39.56   N       ATOM   530   CZ   ARG   A   74   −4.863   31.571   −2.383   1.00   40.38   C       ATOM   531   NH1   ARG   A   74   −6.001   31.116   −2.916   1.00   38.53   N       ATOM   532   NH2   ARG   A   74   −4.767   31.798   −1.085   1.00   37.96   N       ATOM   533   C   ARG   A   74   0.553   31.020   −3.470   1.00   31.04   C       ATOM   534   O   ARG   A   74   0.638   30.847   −2.258   1.00   32.22   O       ATOM   535   N   THR   A   75   1.075   32.077   −4.084   1.00   33.16   N       ATOM   536   CA   THR   A   75   1.679   33.193   −3.289   1.00   34.65   C       ATOM   537   CB   THR   A   75   2.319   34.284   −4.147   1.00   34.94   C       ATOM   538   OG1   THR   A   75   1.299   34.906   −4.943   1.00   31.24   O       ATOM   539   CG2   THR   A   75   3.385   33.710   −5.035   1.00   38.97   C       ATOM   540   C   THR   A   75   0.649   33.872   −2.415   1.00   32.75   C       ATOM   541   O   THR   A   75   −0.566   33.639   −2.562   1.00   30.37   O       ATOM   542   N   GLY   A   76   1.134   34.708   −1.493   1.00   36.03   N       ATOM   543   CA   GLY   A   76   0.280   35.638   −0.751   1.00   34.99   C       ATOM   544   C   GLY   A   76   −0.168   36.709   −1.711   1.00   34.57   C       ATOM   545   O   GLY   A   76   0.262   36.700   −2.865   1.00   35.49   O       ATOM   546   N   TRP   A   77   −1.032   37.612   −1.238   1.00   32.47   N       ATOM   547   CA   TRP   A   77   −1.626   38.650   −2.085   1.00   34.91   C       ATOM   548   CB   TRP   A   77   −2.565   39.510   −1.255   1.00   33.83   C       ATOM   549   CG   TRP   A   77   −3.507   40.357   −2.092   1.00   38.76   C       ATOM   550   CD1   TRP   A   77   −4.293   39.951   −3.139   1.00   36.42   C       ATOM   551   NE1   TRP   A   77   −4.986   41.040   −3.659   1.00   35.07   N       ATOM   552   CE2   TRP   A   77   −4.662   42.153   −2.933   1.00   38.58   C       ATOM   553   CD2   TRP   A   77   −3.735   41.760   −1.937   1.00   42.72   C       ATOM   554   CE3   TRP   A   77   −3.244   42.726   −1.047   1.00   45.06   C       ATOM   555   CZ3   TRP   A   77   −3.675   44.034   −1.182   1.00   37.42   C       ATOM   556   CH2   TRP   A   77   −4.611   44.396   −2.177   1.00   39.82   C       ATOM   557   CZ2   TRP   A   77   −5.117   43.471   −3.055   1.00   41.18   C       ATOM   558   C   TRP   A   77   −0.528   39.545   −2.587   1.00   34.98   C       ATOM   559   O   TRP   A   77   0.240   40.023   −1.792   1.00   35.74   O       ATOM   560   N   VAL   A   78   −0.450   39.804   −3.888   1.00   38.30   N       ATOM   561   CA   VAL   A   78   0.580   40.746   −4.342   1.00   39.04   C       ATOM   562   CB   VAL   A   78   1.558   40.141   −5.392   1.00   39.37   C       ATOM   563   CG1   VAL   A   78   2.797   41.050   −5.563   1.00   39.09   C       ATOM   564   CG2   VAL   A   78   1.994   38.700   −4.983   1.00   33.31   C       ATOM   565   C   VAL   A   78   −0.020   42.079   −4.854   1.00   42.68   C       ATOM   566   O   VAL   A   78   −0.694   42.105   −5.910   1.00   41.94   O       ATOM   567   N   PRO   A   79   0.235   43.176   −4.110   1.00   42.96   N       ATOM   568   CA   PRO   A   79   −0.097   44.504   −4.588   1.00   46.35   C       ATOM   569   CB   PRO   A   79   0.378   45.420   −3.449   1.00   44.48   C       ATOM   570   CG   PRO   A   79   0.432   44.527   −2.236   1.00   38.83   C       ATOM   571   CD   PRO   A   79   0.876   43.222   −2.777   1.00   41.53   C       ATOM   572   C   PRO   A   79   0.611   44.806   −5.934   1.00   49.47   C       ATOM   573   O   PRO   A   79   1.832   44.949   −6.009   1.00   51.20   O       ATOM   574   N   ARG   A   80   −0.183   44.829   −6.997   1.00   53.14   N       ATOM   575   CA   ARG   A   80   0.249   45.329   −8.281   1.00   54.18   C       ATOM   576   CB   ARG   A   80   −0.769   44.923   −9.340   1.00   55.34   C       ATOM   577   CG   ARG   A   80   −0.888   45.833   −10.533   1.00   51.62   C       ATOM   578   CD   ARG   A   80   −2.346   45.943   −10.982   1.00   47.92   C       ATOM   579   NE   ARG   A   80   −3.010   47.189   −10.538   1.00   43.68   N       ATOM   580   CZ   ARG   A   80   −2.977   48.363   −11.174   1.00   53.21   C       ATOM   581   NH1   ARG   A   80   −2.282   48.541   −12.304   1.00   48.15   N       ATOM   582   NH2   ARG   A   80   −3.642   49.389   −10.660   1.00   50.73   N       ATOM   583   C   ARG   A   80   0.281   46.825   −8.058   1.00   56.38   C       ATOM   584   O   ARG   A   80   −0.765   47.478   −8.004   1.00   57.66   O       ATOM   585   N   ARG   A   81   1.476   47.362   −7.852   1.00   57.34   N       ATOM   586   CA   ARG   A   81   1.607   48.768   −7.490   1.00   58.23   C       ATOM   587   CB   ARG   A   81   3.054   49.083   −7.124   1.00   58.75   C       ATOM   588   CG   ARG   A   81   3.430   48.515   −5.765   1.00   57.81   C       ATOM   589   CD   ARG   A   81   4.811   47.914   −5.769   1.00   65.79   C       ATOM   590   NE   ARG   A   81   4.846   46.682   −4.989   1.00   69.25   N       ATOM   591   CZ   ARG   A   81   5.910   46.228   −4.334   1.00   71.96   C       ATOM   592   NH1   ARG   A   81   7.049   46.912   −4.349   1.00   73.08   N       ATOM   593   NH2   ARG   A   81   5.830   45.086   −3.655   1.00   75.90   N       ATOM   594   C   ARG   A   81   1.057   49.687   −8.584   1.00   59.36   C       ATOM   595   O   ARG   A   81   −0.012   50.285   −8.418   1.00   60.97   O       ATOM   596   N   GLY   A   82   1.775   49.786   −9.698   1.00   57.47   N       ATOM   597   CA   GLY   A   82   1.291   50.512   −10.849   1.00   56.99   C       ATOM   598   C   GLY   A   82   1.528   49.695   −12.092   1.00   56.65   C       ATOM   599   O   GLY   A   82   1.475   50.219   −13.206   1.00   56.18   O       ATOM   600   N   ALA   A   83   1.801   48.407   −11.892   1.00   55.51   N       ATOM   601   CA   ALA   A   83   2.078   47.474   −12.984   1.00   55.06   C       ATOM   602   CB   ALA   A   83   2.622   46.159   −12.439   1.00   53.08   C       ATOM   603   C   ALA   A   83   0.877   47.208   −13.868   1.00   54.91   C       ATOM   604   O   ALA   A   83   −0.272   47.183   −13.416   1.00   56.83   O       ATOM   605   N   VAL   A   84   1.156   46.989   −15.140   1.00   55.31   N       ATOM   606   CA   VAL   A   84   0.123   46.541   −16.053   1.00   56.06   C       ATOM   607   CB   VAL   A   84   −0.135   47.546   −17.203   1.00   56.51   C       ATOM   608   CG1   VAL   A   84   −0.933   46.892   −18.338   1.00   54.38   C       ATOM   609   CG2   VAL   A   84   −0.863   48.773   −16.661   1.00   51.88   C       ATOM   610   C   VAL   A   84   0.555   45.187   −16.569   1.00   56.01   C       ATOM   611   O   VAL   A   84   −0.244   44.242   −16.603   1.00   57.12   O       ATOM   612   N   HIS   A   85   1.818   45.103   −16.965   1.00   52.37   N       ATOM   613   CA   HIS   A   85   2.404   43.814   −17.268   1.00   52.72   C       ATOM   614   CB   HIS   A   85   2.900   43.727   −18.711   1.00   52.43   C       ATOM   615   CG   HIS   A   85   1.810   43.911   −19.713   1.00   54.23   C       ATOM   616   ND1   HIS   A   85   1.059   42.864   −20.195   1.00   50.36   N       ATOM   617   CE1   HIS   A   85   0.154   43.327   −21.038   1.00   53.21   C       ATOM   618   NE2   HIS   A   85   0.284   44.639   −21.109   1.00   54.30   N       ATOM   619   CD2   HIS   A   85   1.308   45.031   −20.283   1.00   52.00   C       ATOM   620   C   HIS   A   85   3.485   43.516   −16.267   1.00   49.96   C       ATOM   621   O   HIS   A   85   4.397   44.310   −16.049   1.00   51.17   O       ATOM   622   N   VAL   A   86   3.332   42.366   −15.630   1.00   47.91   N       ATOM   623   CA   VAL   A   86   4.242   41.911   −14.610   1.00   47.10   C       ATOM   624   CB   VAL   A   86   3.431   41.339   −13.414   1.00   49.81   C       ATOM   625   CG1   VAL   A   86   4.221   40.335   −12.580   1.00   46.34   C       ATOM   626   CG2   VAL   A   86   2.883   42.469   −12.557   1.00   49.43   C       ATOM   627   C   VAL   A   86   5.190   40.892   −15.246   1.00   43.83   C       ATOM   628   O   VAL   A   86   4.804   40.171   −16.172   1.00   42.11   O       ATOM   629   N   TYR   A   87   6.438   40.879   −14.781   1.00   39.95   N       ATOM   630   CA   TYR   A   87   7.384   39.865   −15.203   1.00   37.91   C       ATOM   631   CB   TYR   A   87   8.724   40.475   −15.541   1.00   35.88   C       ATOM   632   CG   TYR   A   87   8.811   41.281   −16.830   1.00   42.37   C       ATOM   633   CD1   TYR   A   87   9.646   40.873   −17.871   1.00   44.12   C       ATOM   634   CE1   TYR   A   87   9.779   41.618   −19.021   1.00   47.12   C       ATOM   635   CZ   TYR   A   87   9.074   42.791   −19.142   1.00   39.76   C       ATOM   636   OH   TYR   A   87   9.179   43.539   −20.295   1.00   50.68   O       ATOM   637   CE2   TYR   A   87   8.238   43.218   −18.129   1.00   35.52   C       ATOM   638   CD2   TYR   A   87   8.134   42.478   −16.972   1.00   42.43   C       ATOM   639   C   TYR   A   87   7.576   38.915   −14.037   1.00   31.73   C       ATOM   640   O   TYR   A   87   7.516   39.330   −12.899   1.00   32.92   O       ATOM   641   N   ALA   A   88   7.833   37.653   −14.327   1.00   35.28   N       ATOM   642   CA   ALA   A   88   7.884   36.654   −13.274   1.00   35.57   C       ATOM   643   CB   ALA   A   88   6.521   35.941   −13.123   1.00   35.79   C       ATOM   644   C   ALA   A   88   8.986   35.707   −13.607   1.00   35.70   C       ATOM   645   O   ALA   A   88   8.839   34.833   −14.436   1.00   37.89   O       ATOM   646   N   THR   A   89   10.126   35.931   −12.958   1.00   39.19   N       ATOM   647   CA   THR   A   89   11.313   35.161   −13.225   1.00   38.72   C       ATOM   648   CB   THR   A   89   12.560   36.058   −13.114   1.00   41.64   C       ATOM   649   OG1   THR   A   89   12.479   37.065   −14.125   1.00   39.96   O       ATOM   650   CG2   THR   A   89   13.850   35.262   −13.291   1.00   40.09   C       ATOM   651   C   THR   A   89   11.350   34.037   −12.208   1.00   38.27   C       ATOM   652   O   THR   A   89   11.327   34.284   −11.016   1.00   36.78   O       ATOM   653   N   LEU   A   90   11.391   32.810   −12.712   1.00   41.20   N       ATOM   654   CA   LEU   A   90   11.473   31.597   −11.899   1.00   37.67   C       ATOM   655   CB   LEU   A   90   10.400   30.599   −12.345   1.00   35.91   C       ATOM   656   CG   LEU   A   90   8.978   31.122   −12.557   1.00   42.98   C       ATOM   657   CD1   LEU   A   90   8.040   30.101   −13.249   1.00   37.76   C       ATOM   658   CD2   LEU   A   90   8.416   31.577   −11.249   1.00   37.89   C       ATOM   659   C   LEU   A   90   12.845   30.939   −12.031   1.00   35.29   C       ATOM   660   O   LEU   A   90   13.357   30.750   −13.129   1.00   34.84   O       ATOM   661   N   ARG   A   91   13.414   30.524   −10.908   1.00   32.23   N       ATOM   662   CA   ARG   A   91   14.578   29.704   −10.970   1.00   31.68   C       ATOM   663   CB   ARG   A   91   15.729   30.367   −10.213   1.00   29.26   C       ATOM   664   CG   ARG   A   91   16.186   31.702   −10.714   1.00   39.83   C       ATOM   665   CD   ARG   A   91   17.422   32.123   −9.918   1.00   48.82   C       ATOM   666   NE   ARG   A   91   18.182   33.162   −10.597   1.00   48.28   N       ATOM   667   CZ   ARG   A   91   19.207   32.929   −11.415   1.00   54.96   C       ATOM   668   NH1   ARG   A   91   19.832   33.957   −11.994   1.00   48.94   N       ATOM   669   NH2   ARG   A   91   19.607   31.674   −11.657   1.00   41.81   N       ATOM   670   C   ARG   A   91   14.230   28.388   −10.333   1.00   29.39   C       ATOM   671   O   ARG   A   91   13.650   28.379   −9.267   1.00   30.64   O       ATOM   672   N   PHE   A   92   14.603   27.283   −10.965   1.00   29.19   N       ATOM   673   CA   PHE   A   92   14.179   25.976   −10.483   1.00   28.13   C       ATOM   674   CB   PHE   A   92   12.672   25.695   −10.853   1.00   25.35   C       ATOM   675   CG   PHE   A   92   12.392   25.582   −12.330   1.00   31.38   C       ATOM   676   CD1   PHE   A   92   12.298   24.318   −12.957   1.00   30.18   C       ATOM   677   CE1   PHE   A   92   12.057   24.206   −14.311   1.00   29.16   C       ATOM   678   CZ   PHE   A   92   11.846   25.370   −15.072   1.00   39.78   C       ATOM   679   CE2   PHE   A   92   11.894   26.646   −14.463   1.00   28.29   C       ATOM   680   CD2   PHE   A   92   12.161   26.743   −13.098   1.00   36.30   C       ATOM   681   C   PHE   A   92   15.075   24.896   −10.979   1.00   28.40   C       ATOM   682   O   PHE   A   92   15.770   25.050   −11.991   1.00   33.15   O       ATOM   683   N   THR   A   93   15.024   23.775   −10.304   1.00   28.13   N       ATOM   684   CA   THR   A   93   15.649   22.555   −10.797   1.00   32.26   C       ATOM   685   CB   THR   A   93   16.770   22.043   −9.843   0.50   30.79   C       ATOM   686   OG1   THR   A   93   16.238   21.847   −8.539   0.50   24.15   O       ATOM   687   CG2   THR   A   93   17.892   23.084   −9.725   0.50   28.99   C       ATOM   688   C   THR   A   93   14.528   21.525   −11.044   1.00   35.09   C       ATOM   689   O   THR   A   93   13.461   21.541   −10.390   1.00   37.83   O       ATOM   690   N   MET   A   94   14.748   20.661   −12.022   1.00   37.88   N       ATOM   691   CA   MET   A   94   13.738   19.691   −12.440   1.00   34.08   C       ATOM   692   CB   MET   A   94   13.082   20.163   −13.741   1.00   37.68   C       ATOM   693   CG   MET   A   94   12.132   19.187   −14.384   1.00   31.33   C       ATOM   694   SD   MET   A   94   10.563   19.099   −13.517   1.00   37.28   S       ATOM   695   CE   MET   A   94   10.084   20.829   −13.643   1.00   24.37   C       ATOM   696   C   MET   A   94   14.466   18.376   −12.660   1.00   37.15   C       ATOM   697   O   MET   A   94   15.519   18.350   −13.326   1.00   37.61   O       ATOM   698   N   LEU   A   95   13.968   17.313   −12.049   1.00   32.63   N       ATOM   699   CA   LEU   A   95   14.611   16.001   −12.199   1.00   36.65   C       ATOM   700   CB   LEU   A   95   14.500   15.178   −10.912   1.00   35.07   C       ATOM   701   CG   LEU   A   95   15.630   15.458   −9.894   1.00   40.28   C       ATOM   702   CD1   LEU   A   95   15.447   16.766   −9.120   1.00   39.97   C       ATOM   703   CD2   LEU   A   95   15.799   14.331   −8.946   1.00   41.34   C       ATOM   704   C   LEU   A   95   14.126   15.196   −13.401   1.00   37.05   C       ATOM   705   O   LEU   A   95   12.951   15.165   −13.680   1.00   38.21   O       ATOM   706   N   GLU   A   96   15.064   14.546   −14.093   1.00   40.05   N       ATOM   707   CA   GLU   A   96   14.788   13.649   −15.213   1.00   39.08   C       ATOM   708   CB   GLU   A   96   16.103   13.106   −15.779   1.00   40.73   C       ATOM   709   CG   GLU   A   96   15.936   12.029   −16.850   1.00   41.96   C       ATOM   710   CD   GLU   A   96   17.259   11.583   −17.456   1.00   43.00   C       ATOM   711   OE1   GLU   A   96   18.244   11.364   −16.718   1.00   46.73   O       ATOM   712   OE2   GLU   A   96   17.299   11.443   −18.693   1.00   54.87   O       ATOM   713   C   GLU   A   96   13.931   12.497   −14.738   1.00   38.39   C       ATOM   714   O   GLU   A   96   14.320   11.774   −13.818   1.00   40.49   O       ATOM   715   N   CYS   A   97   12.764   12.313   −15.372   1.00   40.12   N       ATOM   716   CA   CYS   A   97   11.810   11.294   −14.934   1.00   39.96   C       ATOM   717   CB   CYS   A   97   10.527   11.350   −15.772   1.00   43.34   C       ATOM   718   SG   CYS   A   97   9.358   12.560   −15.204   1.00   46.32   S       ATOM   719   C   CYS   A   97   12.397   9.893   −14.973   1.00   41.63   C       ATOM   720   O   CYS   A   97   12.295   9.135   −13.992   1.00   41.45   O       ATOM   721   N   LEU   A   98   13.045   9.563   −16.089   1.00   45.11   N       ATOM   722   CA   LEU   A   98   13.628   8.226   −16.258   1.00   49.04   C       ATOM   723   CB   LEU   A   98   13.860   7.892   −17.743   1.00   51.09   C       ATOM   724   CG   LEU   A   98   12.548   7.587   −18.510   1.00   51.68   C       ATOM   725   CD1   LEU   A   98   12.708   7.541   −20.017   1.00   49.01   C       ATOM   726   CD2   LEU   A   98   11.843   6.315   −18.019   1.00   57.57   C       ATOM   727   C   LEU   A   98   14.859   7.951   −15.405   1.00   49.53   C       ATOM   728   O   LEU   A   98   15.338   6.828   −15.373   1.00   47.03   O       ATOM   729   N   SER   A   99   15.338   8.969   −14.688   1.00   52.06   N       ATOM   730   CA   SER   A   99   16.509   8.844   −13.803   1.00   53.05   C       ATOM   731   CB   SER   A   99   17.356   10.125   −13.826   1.00   53.42   C       ATOM   732   OG   SER   A   99   16.784   11.140   −12.992   1.00   59.05   O       ATOM   733   C   SER   A   99   16.081   8.591   −12.366   1.00   55.03   C       ATOM   734   O   SER   A   99   16.879   8.135   −11.542   1.00   53.98   O       ATOM   735   N   LEU   A   100   14.828   8.926   −12.060   1.00   57.16   N       ATOM   736   CA   LEU   A   100   14.355   8.903   −10.689   1.00   58.91   C       ATOM   737   CB   LEU   A   100   13.036   9.658   −10.554   1.00   57.21   C       ATOM   738   CG   LEU   A   100   12.907   11.112   −10.971   1.00   51.47   C       ATOM   739   CD1   LEU   A   100   11.448   11.472   −10.926   1.00   45.58   C       ATOM   740   CD2   LEU   A   100   13.689   12.003   −10.050   1.00   48.85   C       ATOM   741   C   LEU   A   100   14.147   7.471   −10.250   1.00   63.37   C       ATOM   742   O   LEU   A   100   13.775   6.629   −11.062   1.00   63.99   O       ATOM   743   N   PRO   A   101   14.391   7.187   −8.960   1.00   66.45   N       ATOM   744   CA   PRO   A   101   13.936   5.891   −8.477   1.00   67.84   C       ATOM   745   CB   PRO   A   101   14.775   5.656   −7.218   1.00   68.56   C       ATOM   746   CG   PRO   A   101   15.326   7.009   −6.814   1.00   68.23   C       ATOM   747   CD   PRO   A   101   15.054   7.995   −7.916   1.00   66.48   C       ATOM   748   C   PRO   A   101   12.440   5.954   −8.161   1.00   69.98   C       ATOM   749   O   PRO   A   101   11.956   6.967   −7.632   1.00   72.74   O       ATOM   750   N   ARG   A   102   11.721   4.899   −8.540   1.00   69.84   N       ATOM   751   CA   ARG   A   102   10.292   4.709   −8.226   1.00   69.18   C       ATOM   752   CB   ARG   A   102   10.066   4.608   −6.705   1.00   68.31   C       ATOM   753   C   ARG   A   102   9.309   5.706   −8.876   1.00   68.61   C       ATOM   754   O   ARG   A   102   8.196   5.884   −8.384   1.00   66.90   O       ATOM   755   N   ALA   A   103   9.712   6.321   −9.991   1.00   69.15   N       ATOM   756   CA   ALA   A   103   8.840   7.246   −10.735   1.00   68.27   C       ATOM   757   CB   ALA   A   103   9.659   8.135   −11.660   1.00   68.20   C       ATOM   758   C   ALA   A   103   7.751   6.512   −11.519   1.00   67.94   C       ATOM   759   O   ALA   A   103   8.043   5.742   −12.430   1.00   69.95   O       ATOM   760   N   GLY   A   104   6.496   6.761   −11.159   1.00   67.03   N       ATOM   761   CA   GLY   A   104   5.353   6.130   −11.813   1.00   65.29   C       ATOM   762   C   GLY   A   104   5.013   6.728   −13.168   1.00   64.79   C       ATOM   763   O   GLY   A   104   5.795   7.490   −13.734   1.00   64.68   O       ATOM   764   N   ARG   A   105   3.835   6.371   −13.681   1.00   64.75   N       ATOM   765   CA   ARG   A   105   3.313   6.884   −14.958   1.00   62.98   C       ATOM   766   CB   ARG   A   105   2.082   6.076   −15.373   1.00   63.28   C       ATOM   767   C   ARG   A   105   2.960   8.380   −14.900   1.00   60.94   C       ATOM   768   O   ARG   A   105   2.906   9.062   −15.932   1.00   61.36   O       ATOM   769   N   SER   A   106   2.738   8.884   −13.690   1.00   58.17   N       ATOM   770   CA   SER   A   106   2.346   10.276   −13.477   1.00   56.11   C       ATOM   771   CB   SER   A   106   1.752   10.438   −12.066   1.00   56.25   C       ATOM   772   OG   SER   A   106   1.128   11.702   −11.881   1.00   62.27   O       ATOM   773   C   SER   A   106   3.492   11.282   −13.733   1.00   52.57   C       ATOM   774   O   SER   A   106   3.240   12.458   −13.955   1.00   51.79   O       ATOM   775   N   CYS   A   107   4.736   10.802   −13.767   1.00   48.78   N       ATOM   776   CA   CYS   A   107   5.914   11.679   −13.824   1.00   45.90   C       ATOM   777   CB   CYS   A   107   7.197   10.838   −13.856   1.00   41.55   C       ATOM   778   SG   CYS   A   107   8.708   11.772   −13.436   1.00   45.62   S       ATOM   779   C   CYS   A   107   5.902   12.687   −14.992   1.00   44.80   C       ATOM   780   O   CYS   A   107   5.721   12.296   −16.133   1.00   45.74   O       ATOM   781   N   LYS   A   108   6.108   13.973   −14.680   1.00   42.56   N       ATOM   782   CA   LYS   A   108   6.171   15.074   −15.656   1.00   38.35   C       ATOM   783   CB   LYS   A   108   5.080   16.126   −15.390   1.00   38.46   C       ATOM   784   CG   LYS   A   108   3.617   15.631   −15.344   1.00   41.65   C       ATOM   785   CD   LYS   A   108   3.130   15.220   −16.728   1.00   48.57   C       ATOM   786   CE   LYS   A   108   1.623   15.055   −16.780   1.00   49.47   C       ATOM   787   NZ   LYS   A   108   1.183   13.739   −16.226   1.00   51.52   N       ATOM   788   C   LYS   A   108   7.512   15.802   −15.536   1.00   39.54   C       ATOM   789   O   LYS   A   108   8.128   15.818   −14.465   1.00   30.07   O       ATOM   790   N   GLU   A   109   7.944   16.427   −16.625   1.00   38.56   N       ATOM   791   CA   GLU   A   109   9.128   17.239   −16.574   1.00   38.64   C       ATOM   792   CB   GLU   A   109   10.181   16.730   −17.560   1.00   39.02   C       ATOM   793   CG   GLU   A   109   11.197   15.800   −16.920   1.00   38.15   C       ATOM   794   CD   GLU   A   109   11.851   14.822   −17.899   1.00   44.21   C       ATOM   795   OE1   GLU   A   109   11.980   15.168   −19.088   1.00   43.35   O       ATOM   796   OE2   GLU   A   109   12.272   13.717   −17.467   1.00   42.06   O       ATOM   797   C   GLU   A   109   8.712   18.710   −16.798   1.00   36.56   C       ATOM   798   O   GLU   A   109   9.471   19.530   −17.304   1.00   34.15   O       ATOM   799   N   THR   A   110   7.487   19.022   −16.383   1.00   38.64   N       ATOM   800   CA   THR   A   110   6.890   20.354   −16.584   1.00   36.73   C       ATOM   801   CB   THR   A   110   6.025   20.451   −17.885   1.00   39.68   C       ATOM   802   OG1   THR   A   110   4.742   19.859   −17.655   1.00   36.91   O       ATOM   803   CG2   THR   A   110   6.686   19.780   −19.096   1.00   41.93   C       ATOM   804   C   THR   A   110   5.997   20.727   −15.410   1.00   37.56   C       ATOM   805   O   THR   A   110   5.683   19.887   −14.551   1.00   38.82   O       ATOM   806   N   PHE   A   111   5.558   21.984   −15.397   1.00   34.68   N       ATOM   807   CA   PHE   A   111   4.613   22.485   −14.422   1.00   36.33   C       ATOM   808   CB   PHE   A   111   5.316   22.834   −13.062   1.00   30.29   C       ATOM   809   CG   PHE   A   111   6.288   24.008   −13.127   1.00   37.23   C       ATOM   810   CD1   PHE   A   111   5.861   25.295   −12.849   1.00   29.32   C       ATOM   811   CE1   PHE   A   111   6.719   26.368   −12.916   1.00   32.48   C       ATOM   812   CZ   PHE   A   111   8.045   26.184   −13.242   1.00   30.71   C       ATOM   813   CE2   PHE   A   111   8.505   24.895   −13.522   1.00   28.43   C       ATOM   814   CD2   PHE   A   111   7.604   23.816   −13.469   1.00   30.30   C       ATOM   815   C   PHE   A   111   3.880   23.675   −15.070   1.00   35.66   C       ATOM   816   O   PHE   A   111   4.361   24.226   −16.043   1.00   37.01   O       ATOM   817   N   THR   A   112   2.709   24.032   −14.559   1.00   34.15   N       ATOM   818   CA   THR   A   112   1.902   25.099   −15.158   1.00   38.08   C       ATOM   819   CB   THR   A   112   0.476   24.609   −15.513   1.00   33.33   C       ATOM   820   OG1   THR   A   112   0.534   23.264   −15.995   1.00   47.68   O       ATOM   821   CG2   THR   A   112   −0.151   25.509   −16.580   1.00   43.08   C       ATOM   822   C   THR   A   112   1.757   26.252   −14.190   1.00   33.68   C       ATOM   823   O   THR   A   112   1.636   26.024   −12.992   1.00   37.19   O       ATOM   824   N   VAL   A   113   1.739   27.477   −14.725   1.00   34.66   N       ATOM   825   CA   VAL   A   113   1.595   28.699   −13.935   1.00   34.20   C       ATOM   826   CB   VAL   A   113   2.762   29.695   −14.172   1.00   34.07   C       ATOM   827   CG1   VAL   A   113   2.620   30.929   −13.250   1.00   34.89   C       ATOM   828   CG2   VAL   A   113   4.084   29.039   −13.945   1.00   33.82   C       ATOM   829   C   VAL   A   113   0.278   29.398   −14.298   1.00   39.57   C       ATOM   830   O   VAL   A   113   −0.137   29.379   −15.457   1.00   42.20   O       ATOM   831   N   PHE   A   114   −0.343   30.032   −13.301   1.00   38.25   N       ATOM   832   CA   PHE   A   114   −1.679   30.608   −13.385   1.00   40.31   C       ATOM   833   CB   PHE   A   114   −2.721   29.729   −12.651   1.00   37.24   C       ATOM   834   CG   PHE   A   114   −3.128   28.487   −13.382   1.00   41.83   C       ATOM   835   CD1   PHE   A   114   −4.214   28.508   −14.269   1.00   36.65   C       ATOM   836   CE1   PHE   A   114   −4.609   27.380   −14.934   1.00   39.00   C       ATOM   837   CZ   PHE   A   114   −3.969   26.144   −14.676   1.00   45.82   C       ATOM   838   CE2   PHE   A   114   −2.897   26.096   −13.756   1.00   47.68   C       ATOM   839   CD2   PHE   A   114   −2.500   27.271   −13.113   1.00   46.54   C       ATOM   840   C   PHE   A   114   −1.569   31.905   −12.622   1.00   41.06   C       ATOM   841   O   PHE   A   114   −0.599   32.136   −11.923   1.00   38.95   O       ATOM   842   N   TYR   A   115   −2.559   32.774   −12.778   1.00   45.00   N       ATOM   843   CA   TYR   A   115   −2.713   33.895   −11.855   1.00   42.70   C       ATOM   844   CB   TYR   A   115   −1.955   35.146   −12.293   1.00   42.83   C       ATOM   845   CG   TYR   A   115   −2.521   35.945   −13.454   1.00   40.85   C       ATOM   846   CD1   TYR   A   115   −3.338   37.058   −13.234   1.00   41.69   C       ATOM   847   CE1   TYR   A   115   −3.841   37.820   −14.326   1.00   48.11   C       ATOM   848   CZ   TYR   A   115   −3.491   37.468   −15.640   1.00   49.33   C       ATOM   849   OH   TYR   A   115   −3.957   38.193   −16.727   1.00   51.63   O       ATOM   850   CE2   TYR   A   115   −2.657   36.384   −15.876   1.00   42.04   C       ATOM   851   CD2   TYR   A   115   −2.175   35.626   −14.771   1.00   46.72   C       ATOM   852   C   TYR   A   115   −4.167   34.175   −11.557   1.00   44.47   C       ATOM   853   O   TYR   A   115   −5.062   33.587   −12.167   1.00   44.61   O       ATOM   854   N   TYR   A   116   −4.389   35.025   −10.565   1.00   42.10   N       ATOM   855   CA   TYR   A   116   −5.712   35.412   −10.169   1.00   41.46   C       ATOM   856   CB   TYR   A   116   −6.248   34.439   −9.125   1.00   45.18   C       ATOM   857   CG   TYR   A   116   −7.594   34.821   −8.566   1.00   44.71   C       ATOM   858   CD1   TYR   A   116   −8.756   34.651   −9.322   1.00   48.20   C       ATOM   859   CE1   TYR   A   116   −9.997   34.998   −8.815   1.00   51.58   C       ATOM   860   CZ   TYR   A   116   −10.091   35.515   −7.532   1.00   48.34   C       ATOM   861   OH   TYR   A   116   −11.322   35.864   −7.042   1.00   50.58   O       ATOM   862   CE2   TYR   A   116   −8.953   35.692   −6.758   1.00   48.96   C       ATOM   863   CD2   TYR   A   116   −7.709   35.339   −7.279   1.00   43.17   C       ATOM   864   C   TYR   A   116   −5.627   36.809   −9.594   1.00   39.41   C       ATOM   865   O   TYR   A   116   −4.892   37.039   −8.643   1.00   39.20   O       ATOM   866   N   GLU   A   117   −6.354   37.755   −10.187   1.00   41.63   N       ATOM   867   CA   GLU   A   117   −6.451   39.109   −9.619   1.00   39.85   C       ATOM   868   CB   GLU   A   117   −6.656   40.172   −10.689   1.00   44.57   C       ATOM   869   CG   GLU   A   117   −5.696   40.238   −11.861   1.00   41.68   C       ATOM   870   CD   GLU   A   117   −5.987   41.478   −12.708   1.00   43.45   C       ATOM   871   OE1   GLU   A   117   −6.151   42.558   −12.099   1.00   39.22   O       ATOM   872   OE2   GLU   A   117   −6.076   41.379   −13.958   1.00   47.74   O       ATOM   873   C   GLU   A   117   −7.645   39.214   −8.703   1.00   40.05   C       ATOM   874   O   GLU   A   117   −8.720   38.631   −8.972   1.00   40.21   O       ATOM   875   N   SER   A   118   −7.496   40.010   −7.649   1.00   38.81   N       ATOM   876   CA   SER   A   118   −8.635   40.341   −6.784   1.00   40.06   C       ATOM   877   CB   SER   A   118   −8.714   39.353   −5.647   1.00   36.38   C       ATOM   878   OG   SER   A   118   −7.464   39.353   −4.975   1.00   41.44   O       ATOM   879   C   SER   A   118   −8.408   41.723   −6.204   1.00   41.25   C       ATOM   880   O   SER   A   118   −7.277   42.107   −5.969   1.00   41.14   O       ATOM   881   N   ASP   A   119   −9.476   42.466   −5.945   1.00   43.52   N       ATOM   882   CA   ASP   A   119   −9.331   43.849   −5.464   1.00   44.39   C       ATOM   883   CB   ASP   A   119   −10.632   44.642   −5.659   1.00   42.41   C       ATOM   884   CG   ASP   A   119   −10.730   45.267   −7.050   1.00   46.99   C       ATOM   885   OD1   ASP   A   119   −9.777   45.987   −7.479   1.00   44.22   O       ATOM   886   OD2   ASP   A   119   −11.768   45.046   −7.708   1.00   53.14   O       ATOM   887   C   ASP   A   119   −8.795   43.944   −4.011   1.00   45.57   C       ATOM   888   O   ASP   A   119   −8.150   44.928   −3.645   1.00   46.79   O       ATOM   889   N   ALA   A   120   −9.059   42.912   −3.208   1.00   42.24   N       ATOM   890   CA   ALA   A   120   −8.488   42.778   −1.873   1.00   41.91   C       ATOM   891   CB   ALA   A   120   −9.523   43.085   −0.814   1.00   41.29   C       ATOM   892   C   ALA   A   120   −7.958   41.342   −1.718   1.00   41.62   C       ATOM   893   O   ALA   A   120   −8.149   40.506   −2.605   1.00   41.95   O       ATOM   894   N   ASP   A   121   −7.279   41.080   −0.607   1.00   40.39   N       ATOM   895   CA   ASP   A   121   −6.760   39.750   −0.304   1.00   38.92   C       ATOM   896   CB   ASP   A   121   −5.603   39.842   0.695   1.00   39.88   C       ATOM   897   CG   ASP   A   121   −4.986   38.485   0.986   1.00   38.88   C       ATOM   898   OD1   ASP   A   121   −5.368   37.528   0.286   1.00   43.21   O       ATOM   899   OD2   ASP   A   121   −4.135   38.370   1.901   1.00   35.63   O       ATOM   900   C   ASP   A   121   −7.877   38.869   0.267   1.00   39.74   C       ATOM   901   O   ASP   A   121   −7.956   38.631   1.469   1.00   40.54   O       ATOM   902   N   THR   A   122   −8.724   38.356   −0.608   1.00   38.18   N       ATOM   903   CA   THR   A   122   −9.920   37.670   −0.167   1.00   42.04   C       ATOM   904   CB   THR   A   122   −11.102   38.158   −0.958   1.00   39.56   C       ATOM   905   OG1   THR   A   122   −10.799   38.009   −2.350   1.00   39.83   O       ATOM   906   CG2   THR   A   122   −11.348   39.643   −0.668   1.00   47.23   C       ATOM   907   C   THR   A   122   −9.819   36.149   −0.322   1.00   43.00   C       ATOM   908   O   THR   A   122   −10.737   35.417   0.059   1.00   45.82   O       ATOM   909   N   ALA   A   123   −8.712   35.668   −0.880   1.00   43.76   N       ATOM   910   CA   ALA   A   123   −8.527   34.207   −1.066   1.00   39.96   C       ATOM   911   CB   ALA   A   123   −7.500   33.946   −2.149   1.00   38.69   C       ATOM   912   C   ALA   A   123   −8.162   33.452   0.231   1.00   39.42   C       ATOM   913   O   ALA   A   123   −7.456   33.976   1.079   1.00   38.76   O       ATOM   914   N   THR   A   124   −8.630   32.207   0.354   1.00   37.16   N       ATOM   915   CA   THR   A   124   −8.381   31.380   1.544   1.00   30.14   C       ATOM   916   CB   THR   A   124   −9.759   31.027   2.267   1.00   27.28   C       ATOM   917   OG1   THR   A   124   −10.609   30.385   1.321   1.00   37.96   O       ATOM   918   CG2   THR   A   124   −10.449   32.264   2.782   1.00   34.09   C       ATOM   919   C   THR   A   124   −7.628   30.114   1.121   1.00   31.09   C       ATOM   920   O   THR   A   124   −7.161   29.992   −0.002   1.00   34.92   O       ATOM   921   N   ALA   A   125   −7.516   29.143   2.006   1.00   34.69   N       ATOM   922   CA   ALA   A   125   −6.966   27.857   1.594   1.00   35.09   C       ATOM   923   CB   ALA   A   125   −6.557   27.037   2.822   1.00   35.57   C       ATOM   924   C   ALA   A   125   −7.905   27.045   0.668   1.00   35.61   C       ATOM   925   O   ALA   A   125   −7.450   26.100   0.025   1.00   35.88   O       ATOM   926   N   LEU   A   126   −9.183   27.433   0.580   1.00   35.52   N       ATOM   927   CA   LEU   A   126   −10.170   26.725   −0.244   1.00   38.01   C       ATOM   928   CB   LEU   A   126   −11.158   25.926   0.629   1.00   40.30   C       ATOM   929   CG   LEU   A   126   −10.687   24.875   1.642   1.00   35.50   C       ATOM   930   CD1   LEU   A   126   −11.925   24.464   2.443   1.00   35.12   C       ATOM   931   CD2   LEU   A   126   −10.053   23.662   0.975   1.00   43.01   C       ATOM   932   C   LEU   A   126   −10.956   27.560   −1.259   1.00   39.41   C       ATOM   933   O   LEU   A   126   −11.697   26.987   −2.064   1.00   38.78   O       ATOM   934   N   THR   A   127   −10.819   28.892   −1.208   1.00   39.87   N       ATOM   935   CA   THR   A   127   −11.417   29.795   −2.201   1.00   40.08   C       ATOM   936   CB   THR   A   127   −12.495   30.751   −1.616   1.00   37.17   C       ATOM   937   OG1   THR   A   127   −11.920   31.565   −0.589   1.00   37.12   O       ATOM   938   CG2   THR   A   127   −13.710   29.964   −1.068   1.00   36.23   C       ATOM   939   C   THR   A   127   −10.309   30.639   −2.849   1.00   38.11   C       ATOM   940   O   THR   A   127   −9.397   31.072   −2.167   1.00   39.91   O       ATOM   941   N   PRO   A   128   −10.389   30.879   −4.160   1.00   38.97   N       ATOM   942   CA   PRO   A   128   −11.419   30.490   −5.120   1.00   38.25   C       ATOM   943   CB   PRO   A   128   −11.309   31.579   −6.193   1.00   37.19   C       ATOM   944   CG   PRO   A   128   −9.917   32.012   −6.167   1.00   36.47   C       ATOM   945   CD   PRO   A   128   −9.318   31.665   −4.813   1.00   41.36   C       ATOM   946   C   PRO   A   128   −11.145   29.112   −5.707   1.00   37.82   C       ATOM   947   O   PRO   A   128   −10.157   28.501   −5.356   1.00   39.53   O       ATOM   948   N   ALA   A   129   −12.025   28.630   −6.581   1.00   39.78   N       ATOM   949   CA   ALA   A   129   −11.854   27.318   −7.208   1.00   41.22   C       ATOM   950   CB   ALA   A   129   −12.845   27.149   −8.367   1.00   44.36   C       ATOM   951   C   ALA   A   129   −10.430   27.106   −7.684   1.00   41.46   C       ATOM   952   O   ALA   A   129   −9.931   27.854   −8.514   1.00   42.01   O       ATOM   953   N   TRP   A   130   −9.781   26.070   −7.148   1.00   41.79   N       ATOM   954   CA   TRP   A   130   −8.420   25.722   −7.528   1.00   40.28   C       ATOM   955   CB   TRP   A   130   −7.839   24.792   −6.481   1.00   40.07   C       ATOM   956   CG   TRP   A   130   −7.519   25.415   −5.177   1.00   37.59   C       ATOM   957   CD1   TRP   A   130   −8.231   25.310   −4.029   1.00   36.75   C       ATOM   958   NE1   TRP   A   130   −7.599   25.972   −3.007   1.00   41.38   N       ATOM   959   CE2   TRP   A   130   −6.447   26.532   −3.490   1.00   37.52   C       ATOM   960   CD2   TRP   A   130   −6.355   26.184   −4.859   1.00   39.29   C       ATOM   961   CE3   TRP   A   130   −5.265   26.625   −5.594   1.00   36.95   C       ATOM   962   CZ3   TRP   A   130   −4.283   27.382   −4.939   1.00   37.64   C       ATOM   963   CH2   TRP   A   130   −4.390   27.671   −3.578   1.00   27.48   C       ATOM   964   CZ2   TRP   A   130   −5.468   27.269   −2.837   1.00   38.20   C       ATOM   965   C   TRP   A   130   −8.357   25.051   −8.897   1.00   42.27   C       ATOM   966   O   TRP   A   130   −8.089   23.840   −9.012   1.00   43.07   O       ATOM   967   N   MET   A   131   −8.590   25.839   −9.940   1.00   42.81   N       ATOM   968   CA   MET   A   131   −8.682   25.324   −11.305   1.00   46.53   C       ATOM   969   CB   MET   A   131   −9.995   24.548   −11.502   1.00   44.82   C       ATOM   970   CG   MET   A   131   −11.234   25.302   −11.084   1.00   50.50   C       ATOM   971   SD   MET   A   131   −12.714   24.275   −10.951   1.00   56.25   S       ATOM   972   CE   MET   A   131   −12.308   23.173   −9.583   1.00   56.94   C       ATOM   973   C   MET   A   131   −8.664   26.499   −12.258   1.00   44.91   C       ATOM   974   O   MET   A   131   −9.043   27.602   −11.872   1.00   42.46   O       ATOM   975   N   GLU   A   132   −8.228   26.265   −13.491   1.00   46.13   N       ATOM   976   CA   GLU   A   132   −8.370   27.253   −14.554   1.00   47.13   C       ATOM   977   CB   GLU   A   132   −7.908   26.671   −15.892   1.00   47.45   C       ATOM   978   CG   GLU   A   132   −7.460   27.716   −16.901   1.00   47.99   C       ATOM   979   CD   GLU   A   132   −6.957   27.101   −18.192   1.00   49.03   C       ATOM   980   OE1   GLU   A   132   −6.709   25.877   −18.212   1.00   56.50   O       ATOM   981   OE2   GLU   A   132   −6.810   27.841   −19.187   1.00   59.16   O       ATOM   982   C   GLU   A   132   −9.811   27.741   −14.665   1.00   50.42   C       ATOM   983   O   GLU   A   132   −10.747   26.942   −14.675   1.00   49.36   O       ATOM   984   N   ASN   A   133   −9.980   29.056   −14.747   1.00   51.67   N       ATOM   985   CA   ASN   A   133   −11.273   29.680   −14.489   1.00   52.45   C       ATOM   986   CB   ASN   A   133   −12.287   29.272   −15.559   1.00   53.87   C       ATOM   987   CG   ASN   A   133   −12.849   30.462   −16.312   1.00   58.00   C       ATOM   988   OD1   ASN   A   133   −12.264   30.925   −17.291   1.00   55.56   O       ATOM   989   ND2   ASN   A   133   −13.991   30.965   −15.857   1.00   60.24   N       ATOM   990   C   ASN   A   133   −11.810   29.341   −13.102   1.00   51.46   C       ATOM   991   O   ASN   A   133   −12.643   28.449   −12.949   1.00   53.60   O       ATOM   992   N   PRO   A   134   −11.326   30.060   −12.094   1.00   48.44   N       ATOM   993   CA   PRO   A   134   −11.125   31.508   −12.207   1.00   46.49   C       ATOM   994   CB   PRO   A   134   −11.608   32.030   −10.853   1.00   48.19   C       ATOM   995   CG   PRO   A   134   −11.380   30.898   −9.917   1.00   44.82   C       ATOM   996   CD   PRO   A   134   −11.634   29.649   −10.713   1.00   45.15   C       ATOM   997   C   PRO   A   134   −9.656   31.862   −12.412   1.00   46.83   C       ATOM   998   O   PRO   A   134   −9.334   33.013   −12.705   1.00   42.89   O       ATOM   999   N   TYR   A   135   −8.778   30.876   −12.256   1.00   43.64   N       ATOM   1000   CA   TYR   A   135   −7.359   31.064   −12.529   1.00   41.33   C       ATOM   1001   CB   TYR   A   135   −6.551   29.927   −11.896   1.00   42.40   C       ATOM   1002   CG   TYR   A   135   −6.391   30.116   −10.420   1.00   38.37   C       ATOM   1003   CD1   TYR   A   135   −5.328   30.856   −9.917   1.00   43.89   C       ATOM   1004   CE1   TYR   A   135   −5.165   31.047   −8.565   1.00   35.67   C       ATOM   1005   CZ   TYR   A   135   −6.073   30.497   −7.686   1.00   40.40   C       ATOM   1006   OH   TYR   A   135   −5.892   30.710   −6.340   1.00   41.61   O       ATOM   1007   CE2   TYR   A   135   −7.143   29.734   −8.147   1.00   40.34   C       ATOM   1008   CD2   TYR   A   135   −7.289   29.543   −9.518   1.00   46.85   C       ATOM   1009   C   TYR   A   135   −7.035   31.247   −14.014   1.00   43.30   C       ATOM   1010   O   TYR   A   135   −7.694   30.675   −14.873   1.00   42.09   O       ATOM   1011   N   ILE   A   136   −6.031   32.078   −14.308   1.00   45.98   N       ATOM   1012   CA   ILE   A   136   −5.689   32.424   −15.693   1.00   45.22   C       ATOM   1013   CB   ILE   A   136   −5.611   33.966   −15.879   1.00   45.25   C       ATOM   1014   CG1   ILE   A   136   −6.674   34.667   −15.018   1.00   43.90   C       ATOM   1015   CD1   ILE   A   136   −6.852   36.169   −15.294   1.00   44.67   C       ATOM   1016   CG2   ILE   A   136   −5.625   34.329   −17.376   1.00   45.40   C       ATOM   1017   C   ILE   A   136   −4.360   31.802   −16.125   1.00   44.75   C       ATOM   1018   O   ILE   A   136   −3.317   32.244   −15.674   1.00   49.92   O       ATOM   1019   N   LYS   A   137   −4.405   30.788   −16.996   1.00   45.67   N       ATOM   1020   CA   LYS   A   137   −3.193   30.056   −17.437   1.00   45.23   C       ATOM   1021   CB   LYS   A   137   −3.550   29.029   −18.517   1.00   46.80   C       ATOM   1022   CG   LYS   A   137   −2.568   27.881   −18.636   1.00   51.30   C       ATOM   1023   CD   LYS   A   137   −2.822   27.038   −19.864   1.00   43.64   C       ATOM   1024   CE   LYS   A   137   −1.485   26.684   −20.499   1.00   52.43   C       ATOM   1025   NZ   LYS   A   137   −1.427   25.316   −21.121   1.00   52.54   N       ATOM   1026   C   LYS   A   137   −2.165   31.036   −17.974   1.00   44.80   C       ATOM   1027   O   LYS   A   137   −2.483   31.823   −18.865   1.00   44.54   O       ATOM   1028   N   VAL   A   138   −0.968   31.044   −17.371   1.00   44.85   N       ATOM   1029   CA   VAL   A   138   0.159   31.840   −17.855   1.00   42.62   C       ATOM   1030   CB   VAL   A   138   1.112   32.308   −16.722   1.00   44.21   C       ATOM   1031   CG1   VAL   A   138   2.292   33.090   −17.295   1.00   42.19   C       ATOM   1032   CG2   VAL   A   138   0.391   33.175   −15.727   1.00   39.45   C       ATOM   1033   C   VAL   A   138   0.926   31.034   −18.905   1.00   47.65   C       ATOM   1034   O   VAL   A   138   1.017   31.471   −20.063   1.00   50.24   O       ATOM   1035   N   ASP   A   139   1.449   29.855   −18.516   1.00   48.26   N       ATOM   1036   CA   ASP   A   139   2.147   28.942   −19.445   1.00   47.50   C       ATOM   1037   CB   ASP   A   139   3.486   29.565   −19.865   1.00   49.54   C       ATOM   1038   CG   ASP   A   139   3.863   29.271   −21.313   1.00   55.87   C       ATOM   1039   OD1   ASP   A   139   2.962   29.260   −22.189   1.00   55.59   O       ATOM   1040   OD2   ASP   A   139   5.078   29.094   −21.572   1.00   56.27   O       ATOM   1041   C   ASP   A   139   2.384   27.557   −18.816   1.00   46.73   C       ATOM   1042   O   ASP   A   139   2.370   27.425   −17.603   1.00   46.01   O       ATOM   1043   N   THR   A   140   2.571   26.533   −19.648   1.00   46.52   N       ATOM   1044   CA   THR   A   140   3.020   25.213   −19.200   1.00   46.71   C       ATOM   1045   CB   THR   A   140   2.359   24.089   −20.025   1.00   45.93   C       ATOM   1046   OG1   THR   A   140   0.941   24.093   −19.804   1.00   54.04   O       ATOM   1047   CG2   THR   A   140   2.891   22.720   −19.639   1.00   47.66   C       ATOM   1048   C   THR   A   140   4.552   25.235   −19.364   1.00   47.71   C       ATOM   1049   O   THR   A   140   5.044   25.308   −20.489   1.00   51.63   O       ATOM   1050   N   VAL   A   141   5.286   25.212   −18.245   1.00   45.47   N       ATOM   1051   CA   VAL   A   141   6.731   25.536   −18.205   1.00   43.47   C       ATOM   1052   CB   VAL   A   141   7.122   26.334   −16.913   1.00   43.73   C       ATOM   1053   CG1   VAL   A   141   8.620   26.701   −16.885   1.00   39.47   C       ATOM   1054   CG2   VAL   A   141   6.309   27.599   −16.782   1.00   41.94   C       ATOM   1055   C   VAL   A   141   7.551   24.264   −18.277   1.00   45.44   C       ATOM   1056   O   VAL   A   141   7.346   23.347   −17.484   1.00   42.78   O       ATOM   1057   N   ALA   A   142   8.479   24.214   −19.232   1.00   46.34   N       ATOM   1058   CA   ALA   A   142   9.357   23.061   −19.394   1.00   44.60   C       ATOM   1059   CB   ALA   A   142   9.303   22.534   −20.807   1.00   43.31   C       ATOM   1060   C   ALA   A   142   10.784   23.412   −19.003   1.00   44.91   C       ATOM   1061   O   ALA   A   142   11.166   24.586   −18.984   1.00   44.97   O       ATOM   1062   N   ALA   A   143   11.548   22.371   −18.673   1.00   45.80   N       ATOM   1063   CA   ALA   A   143   12.940   22.477   −18.238   1.00   43.20   C       ATOM   1064   CB   ALA   A   143   13.218   21.450   −17.176   1.00   42.14   C       ATOM   1065   C   ALA   A   143   13.871   22.258   −19.422   1.00   44.18   C       ATOM   1066   O   ALA   A   143   13.738   21.272   −20.138   1.00   44.34   O       ATOM   1067   N   GLU   A   144   14.822   23.174   −19.606   1.00   45.90   N       ATOM   1068   CA   GLU   A   144   15.860   23.046   −20.625   1.00   45.98   C       ATOM   1069   CB   GLU   A   144   16.443   24.409   −21.000   1.00   46.26   C       ATOM   1070   C   GLU   A   144   16.952   22.147   −20.105   1.00   46.83   C       ATOM   1071   O   GLU   A   144   17.680   21.548   −20.886   1.00   47.83   O       ATOM   1072   N   HIS   A   145   17.062   22.066   −18.771   1.00   47.47   N       ATOM   1073   CA   HIS   A   145   18.045   21.228   −18.103   1.00   43.60   C       ATOM   1074   CB   HIS   A   145   19.171   22.083   −17.531   1.00   41.41   C       ATOM   1075   CG   HIS   A   145   19.817   22.965   −18.550   1.00   49.97   C       ATOM   1076   ND1   HIS   A   145   20.679   22.482   −19.514   1.00   50.33   N       ATOM   1077   CE1   HIS   A   145   21.067   23.480   −20.288   1.00   55.83   C       ATOM   1078   NE2   HIS   A   145   20.470   24.585   −19.876   1.00   50.08   N       ATOM   1079   CD2   HIS   A   145   19.686   24.289   −18.790   1.00   50.75   C       ATOM   1080   C   HIS   A   145   17.436   20.361   −17.002   1.00   42.09   C       ATOM   1081   O   HIS   A   145   16.716   20.847   −16.135   1.00   39.62   O       ATOM   1082   N   LEU   A   146   17.765   19.075   −17.051   1.00   40.69   N       ATOM   1083   CA   LEU   A   146   17.326   18.092   −16.075   1.00   41.21   C       ATOM   1084   CB   LEU   A   146   16.898   16.793   −16.786   1.00   43.31   C       ATOM   1085   CG   LEU   A   146   15.739   16.923   −17.800   1.00   45.78   C       ATOM   1086   CD1   LEU   A   146   15.507   15.612   −18.551   1.00   52.48   C       ATOM   1087   CD2   LEU   A   146   14.444   17.386   −17.131   1.00   42.70   C       ATOM   1088   C   LEU   A   146   18.414   17.824   −15.032   1.00   39.66   C       ATOM   1089   O   LEU   A   146   19.626   17.831   −15.328   1.00   40.07   O       ATOM   1090   N   THR   A   147   17.986   17.616   −13.794   1.00   39.07   N       ATOM   1091   CA   THR   A   147   18.914   17.270   −12.723   1.00   36.70   C       ATOM   1092   CB   THR   A   147   18.558   18.011   −11.401   1.00   37.46   C       ATOM   1093   OG1   THR   A   147   18.771   19.419   −11.542   1.00   32.66   O       ATOM   1094   CG2   THR   A   147   19.418   17.501   −10.239   1.00   36.18   C       ATOM   1095   C   THR   A   147   18.847   15.737   −12.552   1.00   39.09   C       ATOM   1096   O   THR   A   147   17.742   15.142   −12.547   1.00   35.10   O       ATOM   1097   N   ARG   A   148   20.014   15.098   −12.483   1.00   37.07   N       ATOM   1098   CA   ARG   A   148   20.090   13.707   −12.031   1.00   37.30   C       ATOM   1099   CB   ARG   A   148   20.887   12.827   −13.001   1.00   36.01   C       ATOM   1100   CG   ARG   A   148   20.231   12.730   −14.351   1.00   42.87   C       ATOM   1101   CD   ARG   A   148   21.219   12.497   −15.435   1.00   46.15   C       ATOM   1102   NE   ARG   A   148   20.558   12.599   −16.732   1.00   49.73   N       ATOM   1103   CZ   ARG   A   148   20.535   13.696   −17.480   1.00   54.09   C       ATOM   1104   NH1   ARG   A   148   21.159   14.796   −17.073   1.00   55.32   N       ATOM   1105   NH2   ARG   A   148   19.886   13.687   −18.643   1.00   48.49   N       ATOM   1106   C   ARG   A   148   20.781   13.718   −10.689   1.00   37.62   C       ATOM   1107   O   ARG   A   148   21.837   14.357   −10.536   1.00   40.62   O       ATOM   1108   N   LYS   A   149   20.197   13.006   −9.729   1.00   33.82   N       ATOM   1109   CA   LYS   A   149   20.717   12.989   −8.374   1.00   38.43   C       ATOM   1110   CB   LYS   A   149   19.724   13.631   −7.391   1.00   36.45   C       ATOM   1111   CG   LYS   A   149   19.349   15.063   −7.677   1.00   39.04   C       ATOM   1112   CD   LYS   A   149   18.851   15.705   −6.408   1.00   31.27   C       ATOM   1113   CE   LYS   A   149   20.019   16.113   −5.543   1.00   33.52   C       ATOM   1114   NZ   LYS   A   149   19.519   16.702   −4.262   1.00   31.74   N       ATOM   1115   C   LYS   A   149   20.888   11.548   −7.968   1.00   39.40   C       ATOM   1116   O   LYS   A   149   20.194   10.675   −8.488   1.00   43.92   O       ATOM   1117   N   ARG   A   150   21.794   11.293   −7.032   1.00   38.52   N       ATOM   1118   CA   ARG   A   150   21.841   9.999   −6.426   1.00   37.72   C       ATOM   1119   CB   ARG   A   150   23.048   9.212   −6.913   1.00   39.83   C       ATOM   1120   CG   ARG   A   150   22.677   7.815   −7.416   1.00   40.68   C       ATOM   1121   CD   ARG   A   150   23.919   7.066   −7.884   1.00   50.69   C       ATOM   1122   NE   ARG   A   150   25.109   7.751   −7.419   1.00   48.61   N       ATOM   1123   CZ   ARG   A   150   25.889   7.366   −6.419   1.00   50.11   C       ATOM   1124   NH1   ARG   A   150   25.659   6.244   −5.744   1.00   40.80   N       ATOM   1125   NH2   ARG   A   150   26.919   8.124   −6.113   1.00   45.14   N       ATOM   1126   C   ARG   A   150   21.770   10.108   −4.899   1.00   41.36   C       ATOM   1127   O   ARG   A   150   22.707   10.607   −4.252   1.00   42.41   O       ATOM   1128   N   PRO   A   151   20.643   9.645   −4.314   1.00   40.04   N       ATOM   1129   CA   PRO   A   151   20.352   9.965   −2.926   1.00   43.16   C       ATOM   1130   CB   PRO   A   151   19.275   8.954   −2.566   1.00   44.97   C       ATOM   1131   CG   PRO   A   151   18.535   8.737   −3.854   1.00   42.32   C       ATOM   1132   CD   PRO   A   151   19.592   8.813   −4.923   1.00   40.05   C       ATOM   1133   C   PRO   A   151   21.600   9.831   −2.018   1.00   47.19   C       ATOM   1134   O   PRO   A   151   22.261   8.794   −2.040   1.00   45.98   O       ATOM   1135   N   GLY   A   152   21.922   10.913   −1.299   1.00   47.18   N       ATOM   1136   CA   GLY   A   152   22.973   10.945   −0.277   1.00   44.93   C       ATOM   1137   C   GLY   A   152   24.383   11.075   −0.813   1.00   43.32   C       ATOM   1138   O   GLY   A   152   25.353   11.273   −0.062   1.00   45.52   O       ATOM   1139   N   ALA   A   153   24.503   10.996   −2.122   1.00   42.03   N       ATOM   1140   CA   ALA   A   153   25.791   10.730   −2.711   1.00   42.81   C       ATOM   1141   CB   ALA   A   153   25.779   9.348   −3.358   1.00   41.08   C       ATOM   1142   C   ALA   A   153   26.205   11.781   −3.717   1.00   43.37   C       ATOM   1143   O   ALA   A   153   27.284   12.352   −3.606   1.00   45.89   O       ATOM   1144   N   GLU   A   154   25.372   12.042   −4.716   1.00   38.19   N       ATOM   1145   CA   GLU   A   154   25.889   12.780   −5.851   1.00   36.09   C       ATOM   1146   CB   GLU   A   154   26.600   11.797   −6.763   1.00   34.29   C       ATOM   1147   CG   GLU   A   154   27.493   12.370   −7.838   1.00   38.73   C       ATOM   1148   CD   GLU   A   154   28.005   11.307   −8.808   1.00   37.40   C       ATOM   1149   OE1   GLU   A   154   27.908   10.093   −8.512   1.00   44.61   O       ATOM   1150   OE2   GLU   A   154   28.460   11.691   −9.898   1.00   40.39   O       ATOM   1151   C   GLU   A   154   24.793   13.458   −6.631   1.00   40.06   C       ATOM   1152   O   GLU   A   154   23.649   12.986   −6.641   1.00   36.30   O       ATOM   1153   N   ALA   A   155   25.169   14.505   −7.359   1.00   38.96   N       ATOM   1154   CA   ALA   A   155   24.204   15.221   −8.171   1.00   37.58   C       ATOM   1155   CB   ALA   A   155   23.518   16.297   −7.339   1.00   41.18   C       ATOM   1156   C   ALA   A   155   24.837   15.832   −9.388   1.00   35.95   C       ATOM   1157   O   ALA   A   155   25.998   16.229   −9.358   1.00   38.79   O       ATOM   1158   N   THR   A   156   24.083   15.898   −10.476   1.00   36.21   N       ATOM   1159   CA   THR   A   156   24.470   16.730   −11.607   1.00   39.46   C       ATOM   1160   CB   THR   A   156   24.920   15.915   −12.849   1.00   41.34   C       ATOM   1161   OG1   THR   A   156   23.904   14.953   −13.171   1.00   43.78   O       ATOM   1162   CG2   THR   A   156   26.249   15.214   −12.622   1.00   38.27   C       ATOM   1163   C   THR   A   156   23.276   17.509   −12.046   1.00   39.87   C       ATOM   1164   O   THR   A   156   22.122   17.050   −11.933   1.00   37.90   O       ATOM   1165   N   GLY   A   157   23.529   18.690   −12.578   1.00   39.18   N       ATOM   1166   CA   GLY   A   157   22.428   19.490   −13.084   1.00   37.13   C       ATOM   1167   C   GLY   A   157   22.780   20.950   −13.226   1.00   35.38   C       ATOM   1168   O   GLY   A   157   23.866   21.396   −12.823   1.00   33.71   O       ATOM   1169   N   LYS   A   158   21.850   21.680   −13.825   1.00   37.34   N       ATOM   1170   CA   LYS   A   158   21.886   23.131   −13.921   1.00   37.93   C       ATOM   1171   CB   LYS   A   158   22.192   23.560   −15.358   1.00   40.53   C       ATOM   1172   C   LYS   A   158   20.519   23.694   −13.496   1.00   39.02   C       ATOM   1173   O   LYS   A   158   19.456   23.080   −13.744   1.00   37.62   O       ATOM   1174   N   VAL   A   159   20.553   24.859   −12.861   1.00   38.06   N       ATOM   1175   CA   VAL   A   159   19.336   25.622   −12.551   1.00   39.03   C       ATOM   1176   CB   VAL   A   159   19.653   26.888   −11.699   1.00   38.12   C       ATOM   1177   CG1   VAL   A   159   18.378   27.596   −11.228   1.00   31.20   C       ATOM   1178   CG2   VAL   A   159   20.479   26.510   −10.502   1.00   42.87   C       ATOM   1179   C   VAL   A   159   18.653   26.083   −13.829   1.00   38.78   C       ATOM   1180   O   VAL   A   159   19.295   26.642   −14.719   1.00   37.57   O       ATOM   1181   N   ASN   A   160   17.347   25.864   −13.911   1.00   37.96   N       ATOM   1182   CA   ASN   A   160   16.555   26.480   −14.968   1.00   40.09   C       ATOM   1183   CB   ASN   A   160   15.339   25.630   −15.291   1.00   37.65   C       ATOM   1184   CG   ASN   A   160   15.735   24.343   −15.924   1.00   41.03   C       ATOM   1185   OD1   ASN   A   160   16.012   24.295   −17.115   1.00   40.31   O       ATOM   1186   ND2   ASN   A   160   15.850   23.304   −15.127   1.00   39.22   N       ATOM   1187   C   ASN   A   160   16.195   27.909   −14.653   1.00   39.02   C       ATOM   1188   O   ASN   A   160   16.020   28.284   −13.504   1.00   40.50   O       ATOM   1189   N   VAL   A   161   16.152   28.736   −15.676   1.00   41.64   N       ATOM   1190   CA   VAL   A   161   15.680   30.090   −15.492   1.00   41.07   C       ATOM   1191   CB   VAL   A   161   16.807   31.143   −15.573   1.00   44.12   C       ATOM   1192   CG1   VAL   A   161   16.272   32.503   −15.082   1.00   42.61   C       ATOM   1193   CG2   VAL   A   161   18.065   30.722   −14.755   1.00   39.53   C       ATOM   1194   C   VAL   A   161   14.604   30.348   −16.546   1.00   42.83   C       ATOM   1195   O   VAL   A   161   14.835   30.185   −17.737   1.00   43.10   O       ATOM   1196   N   LYS   A   162   13.401   30.676   −16.090   1.00   43.32   N       ATOM   1197   CA   LYS   A   162   12.305   31.009   −17.004   1.00   44.78   C       ATOM   1198   CB   LYS   A   162   11.214   29.918   −17.004   1.00   42.48   C       ATOM   1199   CG   LYS   A   162   10.145   30.062   −18.115   1.00   45.76   C       ATOM   1200   CD   LYS   A   162   10.761   29.861   −19.514   1.00   47.76   C       ATOM   1201   CE   LYS   A   162   10.063   30.707   −20.577   1.00   45.12   C       ATOM   1202   NZ   LYS   A   162   10.982   30.966   −21.720   1.00   45.05   N       ATOM   1203   C   LYS   A   162   11.740   32.350   −16.563   1.00   43.17   C       ATOM   1204   O   LYS   A   162   11.532   32.581   −15.374   1.00   42.04   O       ATOM   1205   N   THR   A   163   11.538   33.254   −17.512   1.00   43.54   N       ATOM   1206   CA   THR   A   163   10.833   34.481   −17.193   1.00   39.40   C       ATOM   1207   CB   THR   A   163   11.658   35.711   −17.533   1.00   42.58   C       ATOM   1208   OG1   THR   A   163   12.816   35.742   −16.676   1.00   44.30   O       ATOM   1209   CG2   THR   A   163   10.846   37.006   −17.339   1.00   29.43   C       ATOM   1210   C   THR   A   163   9.516   34.409   −17.951   1.00   40.40   C       ATOM   1211   O   THR   A   163   9.499   34.187   −19.154   1.00   42.46   O       ATOM   1212   N   LEU   A   164   8.427   34.532   −17.211   1.00   39.29   N       ATOM   1213   CA   LEU   A   164   7.082   34.513   −17.756   1.00   41.09   C       ATOM   1214   CB   LEU   A   164   6.223   33.580   −16.903   1.00   37.65   C       ATOM   1215   CG   LEU   A   164   6.527   32.079   −17.062   1.00   34.39   C       ATOM   1216   CD1   LEU   A   164   5.534   31.295   −16.280   1.00   33.44   C       ATOM   1217   CD2   LEU   A   164   6.491   31.624   −18.505   1.00   30.97   C       ATOM   1218   C   LEU   A   164   6.520   35.944   −17.753   1.00   41.72   C       ATOM   1219   O   LEU   A   164   6.925   36.765   −16.935   1.00   41.65   O       ATOM   1220   N   ARG   A   165   5.618   36.240   −18.685   1.00   46.79   N       ATOM   1221   CA   ARG   A   165   4.950   37.552   −18.728   1.00   48.66   C       ATOM   1222   CB   ARG   A   165   5.210   38.285   −20.048   1.00   49.34   C       ATOM   1223   CG   ARG   A   165   4.630   39.706   −20.067   1.00   54.33   C       ATOM   1224   CD   ARG   A   165   5.512   40.673   −19.295   1.00   55.25   C       ATOM   1225   NE   ARG   A   165   6.735   40.850   −20.050   1.00   63.03   N       ATOM   1226   CZ   ARG   A   165   6.834   41.649   −21.098   1.00   59.03   C       ATOM   1227   NH1   ARG   A   165   5.794   42.374   −21.471   1.00   63.76   N       ATOM   1228   NH2   ARG   A   165   7.978   41.732   −21.761   1.00   63.22   N       ATOM   1229   C   ARG   A   165   3.452   37.432   −18.484   1.00   48.66   C       ATOM   1230   O   ARG   A   165   2.830   36.449   −18.860   1.00   52.45   O       ATOM   1231   N   LEU   A   166   2.871   38.466   −17.891   1.00   46.26   N       ATOM   1232   CA   LEU   A   166   1.573   38.344   −17.273   1.00   45.06   C       ATOM   1233   CB   LEU   A   166   1.798   37.906   −15.831   1.00   46.66   C       ATOM   1234   CG   LEU   A   166   0.794   37.731   −14.709   1.00   47.10   C       ATOM   1235   CD1   LEU   A   166   1.252   36.507   −13.939   1.00   47.69   C       ATOM   1236   CD2   LEU   A   166   0.767   38.977   −13.813   1.00   42.28   C       ATOM   1237   C   LEU   A   166   0.835   39.685   −17.337   1.00   44.50   C       ATOM   1238   O   LEU   A   166   1.422   40.738   −17.068   1.00   43.18   O       ATOM   1239   N   GLY   A   167   −0.444   39.627   −17.692   1.00   44.34   N       ATOM   1240   CA   GLY   A   167   −1.286   40.830   −17.818   1.00   46.04   C       ATOM   1241   C   GLY   A   167   −2.089   40.951   −19.117   1.00   46.16   C       ATOM   1242   O   GLY   A   167   −2.277   39.969   −19.851   1.00   48.83   O       ATOM   1243   N   PRO   A   168   −2.604   42.155   −19.404   1.00   44.04   N       ATOM   1244   CA   PRO   A   168   −2.568   43.359   −18.579   1.00   42.19   C       ATOM   1245   CB   PRO   A   168   −3.125   44.437   −19.517   1.00   42.07   C       ATOM   1246   CG   PRO   A   168   −3.995   43.694   −20.446   1.00   47.01   C       ATOM   1247   CD   PRO   A   168   −3.278   42.402   −20.690   1.00   45.76   C       ATOM   1248   C   PRO   A   168   −3.411   43.262   −17.308   1.00   40.54   C       ATOM   1249   O   PRO   A   168   −4.488   42.655   −17.313   1.00   38.18   O       ATOM   1250   N   LEU   A   169   −2.921   43.906   −16.250   1.00   43.31   N       ATOM   1251   CA   LEU   A   169   −3.546   43.889   −14.918   1.00   45.25   C       ATOM   1252   CB   LEU   A   169   −2.505   43.511   −13.880   1.00   45.68   C       ATOM   1253   CG   LEU   A   169   −1.920   42.103   −14.059   1.00   45.04   C       ATOM   1254   CD1   LEU   A   169   −0.397   42.117   −13.926   1.00   50.43   C       ATOM   1255   CD2   LEU   A   169   −2.553   41.196   −13.072   1.00   44.32   C       ATOM   1256   C   LEU   A   169   −4.225   45.212   −14.519   1.00   45.55   C       ATOM   1257   O   LEU   A   169   −3.719   46.295   −14.828   1.00   47.38   O       ATOM   1258   N   SER   A   170   −5.337   45.087   −13.794   1.00   43.84   N       ATOM   1259   CA   SER   A   170   −6.237   46.193   −13.435   1.00   48.14   C       ATOM   1260   CB   SER   A   170   −7.617   45.992   −14.085   1.00   44.83   C       ATOM   1261   OG   SER   A   170   −7.590   46.294   −15.470   1.00   50.91   O       ATOM   1262   C   SER   A   170   −6.484   46.371   −11.941   1.00   47.63   C       ATOM   1263   O   SER   A   170   −6.701   47.502   −11.490   1.00   47.42   O       ATOM   1264   N   LYS   A   171   −6.486   45.257   −11.195   1.00   44.02   N       ATOM   1265   CA   LYS   A   171   −6.991   45.256   −9.817   1.00   43.48   C       ATOM   1266   CB   LYS   A   171   −7.645   43.905   −9.455   1.00   43.41   C       ATOM   1267   CG   LYS   A   171   −8.737   43.410   −10.428   1.00   42.89   C       ATOM   1268   CD   LYS   A   171   −9.921   42.790   −9.677   1.00   45.77   C       ATOM   1269   CE   LYS   A   171   −10.862   42.045   −10.613   1.00   48.97   C       ATOM   1270   NZ   LYS   A   171   −10.337   40.673   −10.938   1.00   43.91   N       ATOM   1271   C   LYS   A   171   −5.904   45.615   −8.823   1.00   42.35   C       ATOM   1272   O   LYS   A   171   −4.744   45.750   −9.203   1.00   43.62   O       ATOM   1273   N   ALA   A   172   −6.262   45.775   −7.554   1.00   40.15   N       ATOM   1274   CA   ALA   A   172   −5.296   46.286   −6.592   1.00   40.64   C       ATOM   1275   CB   ALA   A   172   −5.963   46.540   −5.291   1.00   40.23   C       ATOM   1276   C   ALA   A   172   −4.120   45.317   −6.425   1.00   39.80   C       ATOM   1277   O   ALA   A   172   −2.984   45.726   −6.184   1.00   43.11   O       ATOM   1278   N   GLY   A   173   −4.399   44.031   −6.543   1.00   40.73   N       ATOM   1279   CA   GLY   A   173   −3.365   43.015   −6.434   1.00   37.01   C       ATOM   1280   C   GLY   A   173   −3.745   41.677   −7.017   1.00   38.09   C       ATOM   1281   O   GLY   A   173   −4.871   41.495   −7.536   1.00   35.36   O       ATOM   1282   N   PHE   A   174   −2.814   40.720   −6.921   1.00   30.39   N       ATOM   1283   CA   PHE   A   174   −3.020   39.450   −7.557   1.00   32.18   C       ATOM   1284   CB   PHE   A   174   −2.507   39.466   −9.014   1.00   31.00   C       ATOM   1285   CG   PHE   A   174   −1.004   39.557   −9.138   1.00   33.53   C       ATOM   1286   CD1   PHE   A   174   −0.220   38.387   −9.184   1.00   39.87   C       ATOM   1287   CE1   PHE   A   174   1.160   38.447   −9.279   1.00   40.76   C       ATOM   1288   CZ   PHE   A   174   1.804   39.678   −9.356   1.00   36.30   C       ATOM   1289   CE2   PHE   A   174   1.038   40.872   −9.305   1.00   40.79   C       ATOM   1290   CD2   PHE   A   174   −0.372   40.794   −9.206   1.00   34.74   C       ATOM   1291   C   PHE   A   174   −2.364   38.312   −6.746   1.00   30.68   C       ATOM   1292   O   PHE   A   174   −1.698   38.568   −5.748   1.00   34.70   O       ATOM   1293   N   TYR   A   175   −2.504   37.100   −7.254   1.00   34.65   N       ATOM   1294   CA   TYR   A   175   −1.825   35.917   −6.697   1.00   31.11   C       ATOM   1295   CB   TYR   A   175   −2.859   34.963   −6.139   1.00   36.87   C       ATOM   1296   CG   TYR   A   175   −3.695   35.498   −5.041   1.00   36.55   C       ATOM   1297   CD1   TYR   A   175   −3.246   35.442   −3.722   1.00   34.78   C       ATOM   1298   CE1   TYR   A   175   −4.004   35.942   −2.709   1.00   37.57   C       ATOM   1299   CZ   TYR   A   175   −5.241   36.488   −2.985   1.00   35.98   C       ATOM   1300   OH   TYR   A   175   −6.003   36.966   −1.953   1.00   34.98   O       ATOM   1301   CE2   TYR   A   175   −5.719   36.555   −4.281   1.00   39.64   C       ATOM   1302   CD2   TYR   A   175   −4.939   36.044   −5.306   1.00   34.73   C       ATOM   1303   C   TYR   A   175   −1.215   35.129   −7.800   1.00   34.83   C       ATOM   1304   O   TYR   A   175   −1.844   34.963   −8.839   1.00   36.19   O       ATOM   1305   N   LEU   A   176   −0.063   34.506   −7.533   1.00   34.99   N       ATOM   1306   CA   LEU   A   176   0.505   33.635   −8.516   1.00   36.02   C       ATOM   1307   CB   LEU   A   176   1.978   33.991   −8.765   1.00   32.58   C       ATOM   1308   CG   LEU   A   176   2.568   33.556   −10.093   1.00   33.93   C       ATOM   1309   CD1   LEU   A   176   1.971   34.305   −11.256   1.00   35.00   C       ATOM   1310   CD2   LEU   A   176   4.068   33.794   −10.077   1.00   34.45   C       ATOM   1311   C   LEU   A   176   0.340   32.206   −8.048   1.00   33.83   C       ATOM   1312   O   LEU   A   176   0.550   31.923   −6.871   1.00   34.45   O       ATOM   1313   N   ALA   A   177   −0.007   31.307   −8.961   1.00   31.16   N       ATOM   1314   CA   ALA   A   177   −0.165   29.924   −8.570   1.00   31.94   C       ATOM   1315   CB   ALA   A   177   −1.672   29.506   −8.480   1.00   33.96   C       ATOM   1316   C   ALA   A   177   0.632   28.995   −9.461   1.00   35.75   C       ATOM   1317   O   ALA   A   177   0.909   29.258   −10.658   1.00   35.44   O       ATOM   1318   N   PHE   A   178   1.033   27.900   −8.836   1.00   34.91   N       ATOM   1319   CA   PHE   A   178   1.835   26.896   −9.493   1.00   36.95   C       ATOM   1320   CB   PHE   A   178   3.173   26.699   −8.768   1.00   37.01   C       ATOM   1321   CG   PHE   A   178   4.025   27.931   −8.725   1.00   40.04   C       ATOM   1322   CD1   PHE   A   178   5.022   28.135   −9.690   1.00   34.45   C       ATOM   1323   CE1   PHE   A   178   5.826   29.267   −9.655   1.00   41.39   C       ATOM   1324   CZ   PHE   A   178   5.630   30.221   −8.645   1.00   38.98   C       ATOM   1325   CE2   PHE   A   178   4.617   30.043   −7.695   1.00   38.28   C       ATOM   1326   CD2   PHE   A   178   3.830   28.896   −7.727   1.00   31.99   C       ATOM   1327   C   PHE   A   178   1.019   25.652   −9.361   1.00   36.21   C       ATOM   1328   O   PHE   A   178   0.613   25.292   −8.255   1.00   37.32   O       ATOM   1329   N   GLN   A   179   0.771   25.001   −10.490   1.00   35.99   N       ATOM   1330   CA   GLN   A   179   0.151   23.696   −10.481   1.00   37.46   C       ATOM   1331   CB   GLN   A   179   −1.193   23.726   −11.248   1.00   37.59   C       ATOM   1332   CG   GLN   A   179   −1.779   22.345   −11.528   1.00   34.22   C       ATOM   1333   CD   GLN   A   179   −2.739   22.326   −12.728   1.00   39.93   C       ATOM   1334   OE1   GLN   A   179   −2.403   22.777   −13.817   1.00   45.97   O       ATOM   1335   NE2   GLN   A   179   −3.922   21.754   −12.529   1.00   45.45   N       ATOM   1336   C   GLN   A   179   1.068   22.583   −10.991   1.00   35.94   C       ATOM   1337   O   GLN   A   179   1.540   22.601   −12.105   1.00   33.60   O       ATOM   1338   N   ASP   A   180   1.271   21.592   −10.138   1.00   39.76   N       ATOM   1339   CA   ASP   A   180   2.028   20.410   −10.456   1.00   40.59   C       ATOM   1340   CB   ASP   A   180   2.898   20.092   −9.250   1.00   37.86   C       ATOM   1341   CG   ASP   A   180   3.454   18.706   −9.294   1.00   39.57   C       ATOM   1342   OD1   ASP   A   180   4.226   18.446   −10.237   1.00   39.93   O       ATOM   1343   OD2   ASP   A   180   3.141   17.893   −8.384   1.00   35.30   O       ATOM   1344   C   ASP   A   180   1.106   19.214   −10.744   1.00   40.58   C       ATOM   1345   O   ASP   A   180   0.119   19.009   −10.048   1.00   41.81   O       ATOM   1346   N   GLN   A   181   1.417   18.427   −11.769   1.00   41.23   N       ATOM   1347   CA   GLN   A   181   0.612   17.229   −12.057   1.00   40.16   C       ATOM   1348   CB   GLN   A   181   −0.197   17.361   −13.365   1.00   38.15   C       ATOM   1349   CG   GLN   A   181   −0.923   18.687   −13.561   1.00   41.10   C       ATOM   1350   CD   GLN   A   181   −1.592   18.821   −14.926   1.00   43.97   C       ATOM   1351   OE1   GLN   A   181   −1.923   17.826   −15.577   1.00   43.86   O       ATOM   1352   NE2   GLN   A   181   −1.807   20.066   −15.362   1.00   46.46   N       ATOM   1353   C   GLN   A   181   1.478   15.981   −12.087   1.00   37.45   C       ATOM   1354   O   GLN   A   181   1.018   14.916   −12.448   1.00   38.23   O       ATOM   1355   N   GLY   A   182   2.733   16.097   −11.679   1.00   35.03   N       ATOM   1356   CA   GLY   A   182   3.569   14.916   −11.563   1.00   31.33   C       ATOM   1357   C   GLY   A   182   5.061   15.219   −11.657   1.00   32.94   C       ATOM   1358   O   GLY   A   182   5.853   14.337   −11.965   1.00   33.01   O       ATOM   1359   N   ALA   A   183   5.455   16.446   −11.376   1.00   27.42   N       ATOM   1360   CA   ALA   A   183   6.916   16.789   −11.503   1.00   34.16   C       ATOM   1361   CB   ALA   A   183   7.084   18.245   −11.905   1.00   31.51   C       ATOM   1362   C   ALA   A   183   7.730   16.465   −10.224   1.00   36.88   C       ATOM   1363   O   ALA   A   183   7.165   16.305   −9.146   1.00   38.15   O       ATOM   1364   N   CYS   A   184   9.054   16.330   −10.362   1.00   38.55   N       ATOM   1365   CA   CYS   A   184   9.983   16.326   −9.232   1.00   37.77   C       ATOM   1366   CB   CYS   A   184   10.821   15.026   −9.216   1.00   40.69   C       ATOM   1367   SG   CYS   A   184   11.729   14.712   −7.696   1.00   37.47   S       ATOM   1368   C   CYS   A   184   10.866   17.571   −9.390   1.00   36.58   C       ATOM   1369   O   CYS   A   184   11.808   17.554   −10.162   1.00   34.19   O       ATOM   1370   N   MET   A   185   10.509   18.667   −8.705   1.00   35.34   N       ATOM   1371   CA   MET   A   185   11.161   19.976   −8.863   1.00   36.03   C       ATOM   1372   CB   MET   A   185   10.379   20.827   −9.856   1.00   34.42   C       ATOM   1373   CG   MET   A   185   8.902   21.024   −9.488   1.00   34.05   C       ATOM   1374   SD   MET   A   185   8.089   22.180   −10.598   1.00   36.69   S       ATOM   1375   CE   MET   A   185   8.821   23.708   −10.012   1.00   44.23   C       ATOM   1376   C   MET   A   185   11.317   20.774   −7.567   1.00   29.84   C       ATOM   1377   O   MET   A   185   10.536   20.592   −6.637   1.00   29.27   O       ATOM   1378   N   ALA   A   186   12.397   21.553   −7.464   1.00   30.72   N       ATOM   1379   CA   ALA   A   186   12.518   22.596   −6.450   1.00   27.77   C       ATOM   1380   CB   ALA   A   186   13.910   22.553   −5.745   1.00   25.18   C       ATOM   1381   C   ALA   A   186   12.336   23.979   −7.125   1.00   24.78   C       ATOM   1382   O   ALA   A   186   12.961   24.251   −8.150   1.00   31.56   O       ATOM   1383   N   LEU   A   187   11.565   24.864   −6.507   1.00   27.48   N       ATOM   1384   CA   LEU   A   187   11.519   26.299   −6.879   1.00   27.38   C       ATOM   1385   CB   LEU   A   187   10.101   26.887   −6.703   1.00   30.71   C       ATOM   1386   CG   LEU   A   187   9.980   28.385   −7.052   1.00   29.76   C       ATOM   1387   CD1   LEU   A   187   9.960   28.497   −8.550   1.00   25.31   C       ATOM   1388   CD2   LEU   A   187   8.780   29.029   −6.446   1.00   38.88   C       ATOM   1389   C   LEU   A   187   12.439   27.016   −5.931   1.00   26.96   C       ATOM   1390   O   LEU   A   187   12.136   27.168   −4.765   1.00   31.63   O       ATOM   1391   N   LEU   A   188   13.585   27.419   −6.445   1.00   23.82   N       ATOM   1392   CA   LEU   A   188   14.649   28.033   −5.680   1.00   22.42   C       ATOM   1393   CB   LEU   A   188   15.952   27.928   −6.492   1.00   18.60   C       ATOM   1394   CG   LEU   A   188   16.336   26.464   −6.872   1.00   22.31   C       ATOM   1395   CD1   LEU   A   188   17.713   26.386   −7.539   1.00   28.31   C       ATOM   1396   CD2   LEU   A   188   16.255   25.517   −5.679   1.00   28.43   C       ATOM   1397   C   LEU   A   188   14.302   29.477   −5.412   1.00   22.74   C       ATOM   1398   O   LEU   A   188   14.529   29.936   −4.329   1.00   28.62   O       ATOM   1399   N   SER   A   189   13.673   30.153   −6.382   1.00   27.21   N       ATOM   1400   CA   SER   A   189   13.270   31.519   −6.173   1.00   31.26   C       ATOM   1401   CB   SER   A   189   14.515   32.436   −6.114   1.00   36.03   C       ATOM   1402   OG   SER   A   189   15.019   32.681   −7.411   1.00   31.51   O       ATOM   1403   C   SER   A   189   12.252   32.016   −7.211   1.00   32.45   C       ATOM   1404   O   SER   A   189   12.127   31.446   −8.302   1.00   30.70   O       ATOM   1405   N   LEU   A   190   11.481   33.035   −6.801   1.00   33.70   N       ATOM   1406   CA   LEU   A   190   10.455   33.696   −7.616   1.00   35.24   C       ATOM   1407   CB   LEU   A   190   8.999   33.318   −7.175   1.00   33.65   C       ATOM   1408   CG   LEU   A   190   7.879   34.252   −7.704   1.00   37.98   C       ATOM   1409   CD1   LEU   A   190   7.758   34.196   −9.248   1.00   38.61   C       ATOM   1410   CD2   LEU   A   190   6.494   34.037   −7.064   1.00   34.04   C       ATOM   1411   C   LEU   A   190   10.680   35.193   −7.476   1.00   35.25   C       ATOM   1412   O   LEU   A   190   10.779   35.711   −6.376   1.00   33.56   O       ATOM   1413   N   HIS   A   191   10.780   35.893   −8.594   1.00   37.40   N       ATOM   1414   CA   HIS   A   191   10.920   37.330   −8.519   1.00   38.52   C       ATOM   1415   CB   HIS   A   191   12.402   37.758   −8.720   1.00   37.86   C       ATOM   1416   CG   HIS   A   191   12.617   39.246   −8.734   1.00   41.14   C       ATOM   1417   ND1   HIS   A   191   13.565   39.845   −9.531   1.00   38.74   N       ATOM   1418   CE1   HIS   A   191   13.539   41.156   −9.344   1.00   41.60   C       ATOM   1419   NE2   HIS   A   191   12.627   41.424   −8.430   1.00   40.15   N       ATOM   1420   CD2   HIS   A   191   12.039   40.244   −8.024   1.00   30.90   C       ATOM   1421   C   HIS   A   191   9.921   37.957   −9.487   1.00   39.05   C       ATOM   1422   O   HIS   A   191   9.977   37.744   −10.702   1.00   37.50   O       ATOM   1423   N   LEU   A   192   8.976   38.674   −8.890   1.00   38.54   N       ATOM   1424   CA   LEU   A   192   7.912   39.401   −9.592   1.00   40.13   C       ATOM   1425   CB   LEU   A   192   6.566   39.221   −8.876   1.00   39.90   C       ATOM   1426   CG   LEU   A   192   5.960   37.835   −8.772   1.00   36.90   C       ATOM   1427   CD1   LEU   A   192   4.835   37.864   −7.800   1.00   42.75   C       ATOM   1428   CD2   LEU   A   192   5.498   37.403   −10.150   1.00   33.58   C       ATOM   1429   C   LEU   A   192   8.274   40.859   −9.531   1.00   37.03   C       ATOM   1430   O   LEU   A   192   8.557   41.381   −8.457   1.00   36.49   O       ATOM   1431   N   PHE   A   193   8.241   41.502   −10.687   1.00   38.07   N       ATOM   1432   CA   PHE   A   193   8.650   42.894   −10.841   1.00   36.70   C       ATOM   1433   CB   PHE   A   193   10.216   43.035   −10.959   1.00   29.97   C       ATOM   1434   CG   PHE   A   193   10.802   42.363   −12.180   1.00   31.12   C       ATOM   1435   CD1   PHE   A   193   11.097   43.105   −13.328   1.00   37.50   C       ATOM   1436   CE1   PHE   A   193   11.596   42.500   −14.467   1.00   34.28   C       ATOM   1437   CZ   PHE   A   193   11.853   41.124   −14.481   1.00   45.74   C       ATOM   1438   CE2   PHE   A   193   11.563   40.350   −13.352   1.00   30.73   C       ATOM   1439   CD2   PHE   A   193   11.067   40.985   −12.190   1.00   37.59   C       ATOM   1440   C   PHE   A   193   7.950   43.450   −12.090   1.00   40.02   C       ATOM   1441   O   PHE   A   193   7.271   42.732   −12.840   1.00   44.09   O       ATOM   1442   N   TYR   A   194   8.097   44.747   −12.297   1.00   41.11   N       ATOM   1443   CA   TYR   A   194   7.673   45.348   −13.580   1.00   41.03   C       ATOM   1444   CB   TYR   A   194   6.236   45.880   −13.495   1.00   42.85   C       ATOM   1445   CG   TYR   A   194   6.023   47.133   −12.652   1.00   45.26   C       ATOM   1446   CD1   TYR   A   194   5.865   47.056   −11.268   1.00   45.47   C       ATOM   1447   CE1   TYR   A   194   5.635   48.201   −10.499   1.00   41.30   C       ATOM   1448   CZ   TYR   A   194   5.566   49.425   −11.108   1.00   41.62   C       ATOM   1449   OH   TYR   A   194   5.318   50.549   −10.355   1.00   41.25   O       ATOM   1450   CE2   TYR   A   194   5.703   49.532   −12.480   1.00   44.15   C       ATOM   1451   CD2   TYR   A   194   5.928   48.391   −13.248   1.00   45.95   C       ATOM   1452   C   TYR   A   194   8.650   46.430   −13.974   1.00   41.04   C       ATOM   1453   O   TYR   A   194   9.456   46.856   −13.147   1.00   40.79   O       ATOM   1454   N   LYS   A   195   8.592   46.864   −15.236   1.00   44.73   N       ATOM   1455   CA   LYS   A   195   9.456   47.945   −15.729   1.00   46.28   C       ATOM   1456   CB   LYS   A   195   10.152   47.561   −17.037   1.00   43.48   C       ATOM   1457   CG   LYS   A   195   10.979   46.305   −16.912   1.00   47.45   C       ATOM   1458   CD   LYS   A   195   11.676   45.924   −18.202   1.00   50.29   C       ATOM   1459   CE   LYS   A   195   12.404   44.596   −18.004   1.00   50.32   C       ATOM   1460   NZ   LYS   A   195   12.635   43.846   −19.282   1.00   59.34   N       ATOM   1461   C   LYS   A   195   8.624   49.217   −15.860   1.00   47.80   C       ATOM   1462   O   LYS   A   195   7.537   49.218   −16.454   1.00   45.96   O       ATOM   1463   N   LYS   A   196   9.144   50.290   −15.277   1.00   49.37   N       ATOM   1464   CA   LYS   A   196   8.323   51.432   −14.872   1.00   53.18   C       ATOM   1465   CB   LYS   A   196   9.160   52.333   −13.968   1.00   53.61   C       ATOM   1466   CG   LYS   A   196   8.409   52.877   −12.787   1.00   57.05   C       ATOM   1467   CD   LYS   A   196   9.326   52.905   −11.589   1.00   56.96   C       ATOM   1468   CE   LYS   A   196   9.150   54.183   −10.795   1.00   56.02   C       ATOM   1469   NZ   LYS   A   196   10.319   54.447   −9.912   1.00   49.28   N       ATOM   1470   C   LYS   A   196   7.673   52.246   −16.004   1.00   54.46   C       ATOM   1471   O   LYS   A   196   8.045   52.167   −17.184   1.00   52.26   O       ATOM   1472   OXT   LYS   A   196   6.733   53.018   −15.746   1.00   55.97   O       ATOM   1473   N   ILE   B   31   6.202   17.357   11.661   1.00   52.51   N       ATOM   1474   CA   ILE   B   31   6.652   17.466   13.083   1.00   51.68   C       ATOM   1475   CB   ILE   B   31   7.195   16.099   13.642   1.00   51.99   C       ATOM   1476   CG1   ILE   B   31   8.524   15.693   12.959   1.00   56.45   C       ATOM   1477   CD1   ILE   B   31   9.378   14.656   13.701   1.00   48.38   C       ATOM   1478   CG2   ILE   B   31   6.139   15.008   13.502   1.00   57.59   C       ATOM   1479   C   ILE   B   31   7.694   18.588   13.242   1.00   51.74   C       ATOM   1480   O   ILE   B   31   8.867   18.423   12.904   1.00   49.06   O       ATOM   1481   N   VAL   B   32   7.254   19.737   13.751   1.00   51.69   N       ATOM   1482   CA   VAL   B   32   8.155   20.860   13.927   1.00   49.76   C       ATOM   1483   CB   VAL   B   32   7.409   22.216   13.764   1.00   49.19   C       ATOM   1484   CG1   VAL   B   32   8.381   23.405   13.799   1.00   48.91   C       ATOM   1485   CG2   VAL   B   32   6.606   22.225   12.458   1.00   50.33   C       ATOM   1486   C   VAL   B   32   8.812   20.697   15.292   1.00   51.68   C       ATOM   1487   O   VAL   B   32   8.130   20.724   16.318   1.00   55.62   O       ATOM   1488   N   LEU   B   33   10.130   20.483   15.307   1.00   51.40   N       ATOM   1489   CA   LEU   B   33   10.881   20.426   16.570   1.00   49.84   C       ATOM   1490   CB   LEU   B   33   12.181   19.648   16.400   1.00   49.11   C       ATOM   1491   CG   LEU   B   33   12.026   18.219   15.866   1.00   50.26   C       ATOM   1492   CD1   LEU   B   33   13.092   17.915   14.844   1.00   45.27   C       ATOM   1493   CD2   LEU   B   33   12.059   17.216   17.001   1.00   49.51   C       ATOM   1494   C   LEU   B   33   11.157   21.838   17.081   1.00   51.22   C       ATOM   1495   O   LEU   B   33   10.961   22.817   16.350   1.00   51.79   O       ATOM   1496   N   GLU   B   34   11.587   21.956   18.334   1.00   48.63   N       ATOM   1497   CA   GLU   B   34   11.756   23.283   18.942   1.00   50.49   C       ATOM   1498   CB   GLU   B   34   11.951   23.178   20.458   1.00   52.60   C       ATOM   1499   C   GLU   B   34   12.914   24.043   18.303   1.00   47.30   C       ATOM   1500   O   GLU   B   34   14.019   23.514   18.216   1.00   45.62   O       ATOM   1501   N   PRO   B   35   12.651   25.282   17.841   1.00   46.68   N       ATOM   1502   CA   PRO   B   35   13.663   26.137   17.253   1.00   44.35   C       ATOM   1503   CB   PRO   B   35   12.961   27.492   17.191   1.00   46.18   C       ATOM   1504   CG   PRO   B   35   11.535   27.136   16.959   1.00   44.55   C       ATOM   1505   CD   PRO   B   35   11.319   25.926   17.817   1.00   46.72   C       ATOM   1506   C   PRO   B   35   14.940   26.229   18.079   1.00   46.44   C       ATOM   1507   O   PRO   B   35   14.912   26.212   19.326   1.00   46.98   O       ATOM   1508   N   ILE   B   36   16.058   26.291   17.377   1.00   47.07   N       ATOM   1509   CA   ILE   B   36   17.354   26.348   18.024   1.00   47.75   C       ATOM   1510   CB   ILE   B   36   18.272   25.214   17.548   1.00   45.95   C       ATOM   1511   CG1   ILE   B   36   17.727   23.879   18.073   1.00   46.11   C       ATOM   1512   CD1   ILE   B   36   18.656   22.714   17.974   1.00   48.49   C       ATOM   1513   CG2   ILE   B   36   19.708   25.452   18.031   1.00   52.98   C       ATOM   1514   C   ILE   B   36   17.994   27.717   17.845   1.00   47.45   C       ATOM   1515   O   ILE   B   36   18.367   28.116   16.739   1.00   47.44   O       ATOM   1516   N   TYR   B   37   18.090   28.444   18.951   1.00   48.70   N       ATOM   1517   CA   TYR   B   37   18.714   29.751   18.920   1.00   49.10   C       ATOM   1518   CB   TYR   B   37   18.089   30.679   19.948   1.00   48.08   C       ATOM   1519   CG   TYR   B   37   16.632   30.929   19.657   1.00   53.20   C       ATOM   1520   CD1   TYR   B   37   16.201   32.116   19.037   1.00   55.88   C       ATOM   1521   CE1   TYR   B   37   14.841   32.323   18.784   1.00   52.31   C       ATOM   1522   CZ   TYR   B   37   13.933   31.333   19.131   1.00   53.25   C       ATOM   1523   OH   TYR   B   37   12.585   31.480   18.900   1.00   55.81   O       ATOM   1524   CE2   TYR   B   37   14.343   30.168   19.727   1.00   49.90   C       ATOM   1525   CD2   TYR   B   37   15.675   29.969   19.988   1.00   55.92   C       ATOM   1526   C   TYR   B   37   20.208   29.644   19.095   1.00   48.06   C       ATOM   1527   O   TYR   B   37   20.705   29.188   20.135   1.00   47.00   O       ATOM   1528   N   TRP   B   38   20.902   30.081   18.055   1.00   44.34   N       ATOM   1529   CA   TRP   B   38   22.343   30.031   17.993   1.00   44.89   C       ATOM   1530   CB   TRP   B   38   22.794   29.823   16.533   1.00   45.89   C       ATOM   1531   CG   TRP   B   38   24.191   29.337   16.424   1.00   43.47   C       ATOM   1532   CD1   TRP   B   38   25.320   30.086   16.476   1.00   46.09   C       ATOM   1533   NE1   TRP   B   38   26.432   29.279   16.364   1.00   48.98   N       ATOM   1534   CE2   TRP   B   38   26.015   27.980   16.247   1.00   42.45   C       ATOM   1535   CD2   TRP   B   38   24.610   27.980   16.292   1.00   42.52   C       ATOM   1536   CE3   TRP   B   38   23.930   26.763   16.179   1.00   47.79   C       ATOM   1537   CZ3   TRP   B   38   24.653   25.621   16.043   1.00   46.68   C       ATOM   1538   CH2   TRP   B   38   26.051   25.649   16.007   1.00   47.89   C       ATOM   1539   CZ2   TRP   B   38   26.746   26.821   16.101   1.00   45.11   C       ATOM   1540   C   TRP   B   38   22.912   31.312   18.589   1.00   45.43   C       ATOM   1541   O   TRP   B   38   23.237   32.274   17.882   1.00   41.46   O       ATOM   1542   N   ASN   B   39   22.980   31.315   19.914   1.00   43.47   N       ATOM   1543   CA   ASN   B   39   23.587   32.390   20.669   1.00   47.07   C       ATOM   1544   CB   ASN   B   39   22.561   33.489   21.025   1.00   48.07   C       ATOM   1545   CG   ASN   B   39   21.403   32.981   21.887   1.00   48.17   C       ATOM   1546   OD1   ASN   B   39   21.589   32.193   22.806   1.00   61.41   O       ATOM   1547   ND2   ASN   B   39   20.207   33.467   21.607   1.00   56.57   N       ATOM   1548   C   ASN   B   39   24.274   31.798   21.893   1.00   47.83   C       ATOM   1549   O   ASN   B   39   23.880   30.722   22.380   1.00   48.70   O       ATOM   1550   N   SER   B   40   25.332   32.453   22.361   1.00   50.06   N       ATOM   1551   CA   SER   B   40   26.136   31.882   23.459   1.00   49.21   C       ATOM   1552   CB   SER   B   40   27.442   32.647   23.649   1.00   48.57   C       ATOM   1553   OG   SER   B   40   27.218   33.898   24.280   1.00   47.90   O       ATOM   1554   C   SER   B   40   25.336   31.785   24.776   1.00   50.37   C       ATOM   1555   O   SER   B   40   25.692   30.999   25.677   1.00   51.05   O       ATOM   1556   N   SER   B   41   24.249   32.554   24.875   1.00   48.80   N       ATOM   1557   CA   SER   B   41   23.325   32.428   26.008   1.00   52.76   C       ATOM   1558   CB   SER   B   41   22.504   33.714   26.211   1.00   51.67   C       ATOM   1559   OG   SER   B   41   21.575   33.924   25.161   1.00   57.98   O       ATOM   1560   C   SER   B   41   22.424   31.174   25.920   1.00   54.80   C       ATOM   1561   O   SER   B   41   21.563   30.955   26.782   1.00   55.52   O       ATOM   1562   N   ASN   B   42   22.665   30.329   24.914   1.00   53.48   N       ATOM   1563   CA   ASN   B   42   21.954   29.058   24.777   1.00   52.76   C       ATOM   1564   CB   ASN   B   42   21.929   28.601   23.303   1.00   52.32   C       ATOM   1565   CG   ASN   B   42   20.840   27.578   23.016   1.00   50.95   C       ATOM   1566   OD1   ASN   B   42   20.252   26.984   23.931   1.00   61.15   O       ATOM   1567   ND2   ASN   B   42   20.567   27.360   21.736   1.00   51.55   N       ATOM   1568   C   ASN   B   42   22.582   27.975   25.657   1.00   52.92   C       ATOM   1569   O   ASN   B   42   23.527   27.296   25.236   1.00   52.05   O       ATOM   1570   N   SER   B   43   22.051   27.813   26.868   1.00   52.45   N       ATOM   1571   CA   SER   B   43   22.571   26.817   27.819   1.00   54.85   C       ATOM   1572   CB   SER   B   43   22.026   27.063   29.231   1.00   53.84   C       ATOM   1573   OG   SER   B   43   20.659   26.694   29.333   1.00   57.96   O       ATOM   1574   C   SER   B   43   22.343   25.358   27.378   1.00   54.62   C       ATOM   1575   O   SER   B   43   22.959   24.447   27.926   1.00   56.78   O       ATOM   1576   N   LYS   B   44   21.479   25.152   26.378   1.00   53.79   N       ATOM   1577   CA   LYS   B   44   21.264   23.840   25.758   1.00   51.82   C       ATOM   1578   CB   LYS   B   44   20.148   23.919   24.720   1.00   52.94   C       ATOM   1579   C   LYS   B   44   22.530   23.276   25.109   1.00   50.94   C       ATOM   1580   O   LYS   B   44   22.605   22.071   24.860   1.00   50.22   O       ATOM   1581   N   PHE   B   45   23.504   24.152   24.821   1.00   49.62   N       ATOM   1582   CA   PHE   B   45   24.847   23.737   24.377   1.00   48.32   C       ATOM   1583   CB   PHE   B   45   25.553   24.826   23.572   1.00   47.65   C       ATOM   1584   CG   PHE   B   45   24.955   25.064   22.207   1.00   45.89   C       ATOM   1585   CD1   PHE   B   45   25.111   24.129   21.172   1.00   45.96   C       ATOM   1586   CE1   PHE   B   45   24.572   24.365   19.904   1.00   50.10   C       ATOM   1587   CZ   PHE   B   45   23.862   25.541   19.669   1.00   47.05   C       ATOM   1588   CE2   PHE   B   45   23.710   26.476   20.686   1.00   40.41   C       ATOM   1589   CD2   PHE   B   45   24.253   26.226   21.951   1.00   47.70   C       ATOM   1590   C   PHE   B   45   25.692   23.372   25.580   1.00   49.49   C       ATOM   1591   O   PHE   B   45   26.274   24.243   26.245   1.00   50.60   O       ATOM   1592   N   LEU   B   46   25.767   22.079   25.849   1.00   50.95   N       ATOM   1593   CA   LEU   B   46   26.364   21.592   27.087   1.00   51.22   C       ATOM   1594   CB   LEU   B   46   25.730   20.261   27.487   1.00   51.08   C       ATOM   1595   CG   LEU   B   46   24.203   20.190   27.619   1.00   46.10   C       ATOM   1596   CD1   LEU   B   46   23.796   18.761   27.883   1.00   43.82   C       ATOM   1597   CD2   LEU   B   46   23.662   21.111   28.694   1.00   48.08   C       ATOM   1598   C   LEU   B   46   27.878   21.452   26.985   1.00   54.27   C       ATOM   1599   O   LEU   B   46   28.397   21.095   25.924   1.00   55.19   O       ATOM   1600   N   PRO   B   47   28.592   21.756   28.088   1.00   55.99   N       ATOM   1601   CA   PRO   B   47   30.002   21.439   28.289   1.00   58.57   C       ATOM   1602   CB   PRO   B   47   30.085   21.210   29.807   1.00   58.59   C       ATOM   1603   CG   PRO   B   47   28.908   21.978   30.394   1.00   59.61   C       ATOM   1604   CD   PRO   B   47   28.053   22.487   29.245   1.00   55.29   C       ATOM   1605   C   PRO   B   47   30.423   20.159   27.568   1.00   60.23   C       ATOM   1606   O   PRO   B   47   29.753   19.124   27.703   1.00   60.06   O       ATOM   1607   N   GLY   B   48   31.512   20.242   26.801   1.00   60.39   N       ATOM   1608   CA   GLY   B   48   32.012   19.118   26.020   1.00   60.52   C       ATOM   1609   C   GLY   B   48   31.089   18.599   24.925   1.00   62.42   C       ATOM   1610   O   GLY   B   48   31.405   18.716   23.725   1.00   62.21   O       ATOM   1611   N   ALA   B   49   29.954   18.032   25.348   1.00   61.80   N       ATOM   1612   CA   ALA   B   49   28.988   17.361   24.474   1.00   61.62   C       ATOM   1613   CB   ALA   B   49   27.858   16.757   25.302   1.00   60.60   C       ATOM   1614   C   ALA   B   49   28.420   18.229   23.345   1.00   62.36   C       ATOM   1615   O   ALA   B   49   28.463   17.833   22.180   1.00   64.81   O       ATOM   1616   N   GLY   B   50   27.894   19.404   23.690   1.00   61.93   N       ATOM   1617   CA   GLY   B   50   27.206   20.263   22.722   1.00   60.75   C       ATOM   1618   C   GLY   B   50   25.706   20.038   22.758   1.00   59.01   C       ATOM   1619   O   GLY   B   50   25.154   19.714   23.818   1.00   58.98   O       ATOM   1620   N   LEU   B   51   25.051   20.190   21.607   1.00   56.06   N       ATOM   1621   CA   LEU   B   51   23.600   19.988   21.513   1.00   55.72   C       ATOM   1622   CB   LEU   B   51   22.923   21.197   20.861   1.00   55.78   C       ATOM   1623   CG   LEU   B   51   21.510   21.607   21.317   1.00   56.57   C       ATOM   1624   CD1   LEU   B   51   21.260   23.086   21.016   1.00   54.35   C       ATOM   1625   CD2   LEU   B   51   20.410   20.740   20.712   1.00   51.01   C       ATOM   1626   C   LEU   B   51   23.231   18.687   20.783   1.00   55.37   C       ATOM   1627   O   LEU   B   51   23.654   18.454   19.650   1.00   56.89   O       ATOM   1628   N   VAL   B   52   22.455   17.834   21.449   1.00   52.14   N       ATOM   1629   CA   VAL   B   52   22.091   16.532   20.898   1.00   49.64   C       ATOM   1630   CB   VAL   B   52   22.656   15.331   21.729   1.00   49.25   C       ATOM   1631   CG1   VAL   B   52   22.280   13.976   21.106   1.00   47.08   C       ATOM   1632   CG2   VAL   B   52   24.181   15.425   21.866   1.00   51.63   C       ATOM   1633   C   VAL   B   52   20.576   16.444   20.713   1.00   47.40   C       ATOM   1634   O   VAL   B   52   19.796   16.668   21.658   1.00   44.14   O       ATOM   1635   N   LEU   B   53   20.206   16.136   19.465   1.00   46.22   N       ATOM   1636   CA   LEU   B   53   18.839   16.015   18.990   1.00   46.52   C       ATOM   1637   CB   LEU   B   53   18.545   17.067   17.899   1.00   45.04   C       ATOM   1638   CG   LEU   B   53   18.416   18.522   18.330   1.00   49.63   C       ATOM   1639   CD1   LEU   B   53   18.373   19.404   17.093   1.00   41.47   C       ATOM   1640   CD2   LEU   B   53   17.178   18.711   19.223   1.00   46.52   C       ATOM   1641   C   LEU   B   53   18.710   14.674   18.333   1.00   46.61   C       ATOM   1642   O   LEU   B   53   19.693   14.160   17.789   1.00   45.23   O       ATOM   1643   N   ALA   B   54   17.488   14.136   18.377   1.00   48.27   N       ATOM   1644   CA   ALA   B   54   17.104   12.922   17.662   1.00   51.02   C       ATOM   1645   CB   ALA   B   54   16.871   11.748   18.636   1.00   54.27   C       ATOM   1646   C   ALA   B   54   15.841   13.229   16.845   1.00   52.58   C       ATOM   1647   O   ALA   B   54   14.711   13.093   17.344   1.00   50.37   O       ATOM   1648   N   PRO   B   55   16.035   13.722   15.606   1.00   51.74   N       ATOM   1649   CA   PRO   B   55   14.941   14.004   14.667   1.00   50.37   C       ATOM   1650   CB   PRO   B   55   15.546   15.065   13.753   1.00   48.25   C       ATOM   1651   CG   PRO   B   55   17.011   14.775   13.743   1.00   49.23   C       ATOM   1652   CD   PRO   B   55   17.352   14.098   15.044   1.00   51.76   C       ATOM   1653   C   PRO   B   55   14.538   12.782   13.846   1.00   49.88   C       ATOM   1654   O   PRO   B   55   15.357   11.906   13.592   1.00   49.10   O       ATOM   1655   N   GLN   B   56   13.281   12.748   13.422   1.00   50.05   N       ATOM   1656   CA   GLN   B   56   12.789   11.680   12.590   1.00   49.58   C       ATOM   1657   CB   GLN   B   56   11.439   11.207   13.119   1.00   49.76   C       ATOM   1658   CG   GLN   B   56   11.343   9.697   13.288   1.00   51.96   C       ATOM   1659   CD   GLN   B   56   12.022   9.182   14.553   1.00   53.57   C       ATOM   1660   OE1   GLN   B   56   12.667   9.934   15.296   1.00   48.95   O       ATOM   1661   NE2   GLN   B   56   11.867   7.884   14.805   1.00   44.22   N       ATOM   1662   C   GLN   B   56   12.647   12.193   11.165   1.00   50.12   C       ATOM   1663   O   GLN   B   56   12.295   13.349   10.967   1.00   49.01   O       ATOM   1664   N   ILE   B   57   12.940   11.338   10.185   1.00   50.19   N       ATOM   1665   CA   ILE   B   57   12.631   11.616   8.774   1.00   52.05   C       ATOM   1666   CB   ILE   B   57   12.797   10.340   7.884   1.00   50.70   C       ATOM   1667   CG1   ILE   B   57   14.270   9.879   7.814   1.00   52.97   C       ATOM   1668   CD1   ILE   B   57   15.269   10.917   7.322   1.00   50.34   C       ATOM   1669   CG2   ILE   B   57   12.200   10.527   6.505   1.00   55.73   C       ATOM   1670   C   ILE   B   57   11.211   12.192   8.661   1.00   53.21   C       ATOM   1671   O   ILE   B   57   10.235   11.604   9.151   1.00   52.05   O       ATOM   1672   N   GLY   B   58   11.116   13.365   8.041   1.00   54.38   N       ATOM   1673   CA   GLY   B   58   9.867   14.110   7.975   1.00   56.00   C       ATOM   1674   C   GLY   B   58   9.901   15.371   8.822   1.00   56.89   C       ATOM   1675   O   GLY   B   58   9.095   16.282   8.619   1.00   57.36   O       ATOM   1676   N   ASP   B   59   10.839   15.415   9.769   1.00   57.12   N       ATOM   1677   CA   ASP   B   59   10.966   16.522   10.724   1.00   55.47   C       ATOM   1678   CB   ASP   B   59   12.019   16.195   11.775   1.00   55.05   C       ATOM   1679   C   ASP   B   59   11.341   17.828   10.060   1.00   53.03   C       ATOM   1680   O   ASP   B   59   11.925   17.823   8.984   1.00   53.44   O       ATOM   1681   N   LYS   B   60   10.992   18.933   10.723   1.00   51.30   N       ATOM   1682   CA   LYS   B   60   11.409   20.285   10.345   1.00   47.93   C       ATOM   1683   CB   LYS   B   60   10.238   21.096   9.783   1.00   48.26   C       ATOM   1684   CG   LYS   B   60   9.889   20.884   8.297   1.00   46.39   C       ATOM   1685   CD   LYS   B   60   9.229   22.177   7.740   1.00   47.01   C       ATOM   1686   CE   LYS   B   60   8.534   21.992   6.395   1.00   52.74   C       ATOM   1687   NZ   LYS   B   60   7.991   23.324   5.847   1.00   44.78   N       ATOM   1688   C   LYS   B   60   11.979   20.988   11.586   1.00   46.25   C       ATOM   1689   O   LYS   B   60   11.384   20.949   12.655   1.00   45.18   O       ATOM   1690   N   LEU   B   61   13.142   21.608   11.435   1.00   45.65   N       ATOM   1691   CA   LEU   B   61   13.799   22.335   12.521   1.00   44.72   C       ATOM   1692   CB   LEU   B   61   14.975   21.527   13.077   1.00   45.50   C       ATOM   1693   CG   LEU   B   61   15.939   22.130   14.107   1.00   47.54   C       ATOM   1694   CD1   LEU   B   61   15.354   22.084   15.519   1.00   39.59   C       ATOM   1695   CD2   LEU   B   61   17.286   21.432   14.072   1.00   46.47   C       ATOM   1696   C   LEU   B   61   14.325   23.667   12.016   1.00   42.76   C       ATOM   1697   O   LEU   B   61   14.990   23.713   10.980   1.00   42.46   O       ATOM   1698   N   ASP   B   62   14.022   24.732   12.754   1.00   39.20   N       ATOM   1699   CA   ASP   B   62   14.588   26.045   12.507   1.00   40.51   C       ATOM   1700   CB   ASP   B   62   13.553   27.146   12.773   1.00   38.33   C       ATOM   1701   CG   ASP   B   62   12.304   27.020   11.914   1.00   43.05   C       ATOM   1702   OD1   ASP   B   62   11.233   27.448   12.381   1.00   53.67   O       ATOM   1703   OD2   ASP   B   62   12.363   26.508   10.779   1.00   50.75   O       ATOM   1704   C   ASP   B   62   15.791   26.280   13.419   1.00   40.29   C       ATOM   1705   O   ASP   B   62   15.676   26.176   14.649   1.00   44.71   O       ATOM   1706   N   ILE   B   63   16.941   26.612   12.824   1.00   39.54   N       ATOM   1707   CA   ILE   B   63   18.070   27.149   13.567   1.00   40.77   C       ATOM   1708   CB   ILE   B   63   19.371   26.483   13.157   1.00   41.56   C       ATOM   1709   CG1   ILE   B   63   19.243   24.966   13.300   1.00   38.50   C       ATOM   1710   CD1   ILE   B   63   20.358   24.219   12.616   1.00   50.40   C       ATOM   1711   CG2   ILE   B   63   20.556   27.016   13.981   1.00   41.42   C       ATOM   1712   C   ILE   B   63   18.112   28.688   13.321   1.00   40.07   C       ATOM   1713   O   ILE   B   63   18.179   29.139   12.167   1.00   42.17   O       ATOM   1714   N   ILE   B   64   18.039   29.468   14.402   1.00   40.38   N       ATOM   1715   CA   ILE   B   64   17.839   30.952   14.299   1.00   42.37   C       ATOM   1716   CB   ILE   B   64   16.539   31.409   15.011   1.00   44.09   C       ATOM   1717   CG1   ILE   B   64   15.325   30.676   14.458   1.00   40.39   C       ATOM   1718   CD1   ILE   B   64   15.048   29.389   15.178   1.00   47.96   C       ATOM   1719   CG2   ILE   B   64   16.338   32.965   14.883   1.00   40.44   C       ATOM   1720   C   ILE   B   64   18.945   31.742   14.953   1.00   45.33   C       ATOM   1721   O   ILE   B   64   19.215   31.530   16.138   1.00   44.27   O       ATOM   1722   N   CYS   B   65   19.576   32.658   14.212   1.00   47.81   N       ATOM   1723   CA   CYS   B   65   20.440   33.650   14.849   1.00   50.81   C       ATOM   1724   CB   CYS   B   65   21.625   34.041   13.976   1.00   52.46   C       ATOM   1725   SG   CYS   B   65   22.840   32.737   13.887   1.00   57.22   S       ATOM   1726   C   CYS   B   65   19.604   34.870   15.232   1.00   52.50   C       ATOM   1727   O   CYS   B   65   19.169   35.632   14.361   1.00   51.32   O       ATOM   1728   N   PRO   B   66   19.427   35.090   16.523   1.00   52.38   N       ATOM   1729   CA   PRO   B   66   18.436   36.051   17.007   1.00   56.14   C       ATOM   1730   CB   PRO   B   66   18.428   35.810   18.510   1.00   56.30   C       ATOM   1731   CG   PRO   B   66   18.947   34.448   18.672   1.00   55.10   C       ATOM   1732   CD   PRO   B   66   19.955   34.262   17.611   1.00   53.36   C       ATOM   1733   C   PRO   B   66   18.780   37.503   16.701   1.00   57.91   C       ATOM   1734   O   PRO   B   66   19.943   37.887   16.680   1.00   55.40   O       ATOM   1735   N   LYS   B   67   17.742   38.289   16.445   1.00   61.44   N       ATOM   1736   CA   LYS   B   67   17.760   39.738   16.596   1.00   63.19   C       ATOM   1737   CB   LYS   B   67   16.324   40.238   16.522   1.00   63.03   C       ATOM   1738   CG   LYS   B   67   16.105   41.449   15.671   1.00   63.45   C       ATOM   1739   CD   LYS   B   67   14.634   41.608   15.386   1.00   61.61   C       ATOM   1740   CE   LYS   B   67   14.307   43.020   14.962   1.00   65.44   C       ATOM   1741   NZ   LYS   B   67   13.998   43.916   16.102   1.00   65.01   N       ATOM   1742   C   LYS   B   67   18.341   40.152   17.937   1.00   65.68   C       ATOM   1743   O   LYS   B   67   17.926   39.645   18.972   1.00   66.30   O       ATOM   1744   N   VAL   B   68   19.271   41.098   17.938   1.00   66.29   N       ATOM   1745   CA   VAL   B   68   19.561   41.816   19.174   1.00   67.49   C       ATOM   1746   CB   VAL   B   68   20.942   41.501   19.750   1.00   66.82   C       ATOM   1747   CG1   VAL   B   68   21.073   40.009   20.042   1.00   66.77   C       ATOM   1748   CG2   VAL   B   68   22.021   41.977   18.826   1.00   63.95   C       ATOM   1749   C   VAL   B   68   19.320   43.312   19.154   1.00   68.26   C       ATOM   1750   O   VAL   B   68   20.061   44.068   18.532   1.00   68.98   O       ATOM   1751   N   ASP   B   69   18.285   43.722   19.874   1.00   69.20   N       ATOM   1752   CA   ASP   B   69   17.631   45.029   19.687   1.00   70.92   C       ATOM   1753   CB   ASP   B   69   16.119   44.881   19.934   1.00   69.99   C       ATOM   1754   CG   ASP   B   69   15.638   43.433   19.795   1.00   67.08   C       ATOM   1755   OD1   ASP   B   69   15.978   42.783   18.785   1.00   72.72   O       ATOM   1756   OD2   ASP   B   69   14.922   42.943   20.695   1.00   57.27   O       ATOM   1757   C   ASP   B   69   18.207   46.160   20.561   1.00   72.50   C       ATOM   1758   O   ASP   B   69   19.151   45.945   21.321   1.00   72.58   O       ATOM   1759   N   SER   B   70   17.640   47.363   20.434   1.00   74.73   N       ATOM   1760   CA   SER   B   70   18.004   48.508   21.287   1.00   77.16   C       ATOM   1761   C   SER   B   70   17.679   48.211   22.755   1.00   79.24   C       ATOM   1762   O   SER   B   70   18.492   48.469   23.649   1.00   78.89   O       ATOM   1763   N   LYS   B   71   16.472   47.687   22.980   1.00   81.34   N       ATOM   1764   CA   LYS   B   71   16.098   47.035   24.233   1.00   82.67   C       ATOM   1765   CB   LYS   B   71   14.669   47.409   24.636   1.00   82.35   C       ATOM   1766   C   LYS   B   71   16.220   45.520   24.021   1.00   84.04   C       ATOM   1767   O   LYS   B   71   15.557   44.961   23.145   1.00   84.71   O       ATOM   1768   N   THR   B   72   17.059   44.882   24.841   1.00   84.98   N       ATOM   1769   CA   THR   B   72   17.545   43.485   24.692   1.00   85.61   C       ATOM   1770   CB   THR   B   72   16.758   42.603   23.646   1.00   85.57   C       ATOM   1771   OG1   THR   B   72   15.358   42.607   23.953   1.00   85.29   O       ATOM   1772   CG2   THR   B   72   17.245   41.149   23.662   1.00   85.71   C       ATOM   1773   C   THR   B   72   19.066   43.520   24.425   1.00   85.75   C       ATOM   1774   O   THR   B   72   19.580   42.865   23.508   1.00   85.63   O       ATOM   1775   N   VAL   B   73   19.754   44.316   25.251   1.00   85.63   N       ATOM   1776   CA   VAL   B   73   21.222   44.480   25.269   1.00   85.19   C       ATOM   1777   CB   VAL   B   73   21.959   43.217   25.841   1.00   85.28   C       ATOM   1778   CG1   VAL   B   73   23.410   43.546   26.233   1.00   83.57   C       ATOM   1779   CG2   VAL   B   73   21.210   42.646   27.045   1.00   85.78   C       ATOM   1780   C   VAL   B   73   21.832   44.916   23.925   1.00   84.59   C       ATOM   1781   O   VAL   B   73   21.193   44.830   22.878   1.00   83.42   O       ATOM   1782   N   GLY   B   74   23.063   45.414   23.979   1.00   84.51   N       ATOM   1783   CA   GLY   B   74   23.854   45.647   22.777   1.00   84.58   C       ATOM   1784   C   GLY   B   74   24.647   44.398   22.419   1.00   84.25   C       ATOM   1785   O   GLY   B   74   24.482   43.338   23.053   1.00   85.08   O       ATOM   1786   N   GLN   B   75   25.505   44.526   21.403   1.00   81.57   N       ATOM   1787   CA   GLN   B   75   26.417   43.453   20.965   1.00   78.55   C       ATOM   1788   CB   GLN   B   75   27.350   42.999   22.102   1.00   78.75   C       ATOM   1789   CG   GLN   B   75   28.402   44.045   22.503   1.00   80.96   C       ATOM   1790   CD   GLN   B   75   28.668   44.097   24.009   1.00   83.13   C       ATOM   1791   OE1   GLN   B   75   27.757   43.914   24.820   1.00   84.28   O       ATOM   1792   NE2   GLN   B   75   29.919   44.367   24.384   1.00   81.04   N       ATOM   1793   C   GLN   B   75   25.697   42.268   20.311   1.00   74.88   C       ATOM   1794   O   GLN   B   75   24.789   41.663   20.884   1.00   75.60   O       ATOM   1795   N   TYR   B   76   26.122   41.964   19.091   1.00   70.64   N       ATOM   1796   CA   TYR   B   76   25.579   40.870   18.305   1.00   65.82   C       ATOM   1797   CB   TYR   B   76   25.256   41.387   16.895   1.00   62.96   C       ATOM   1798   CG   TYR   B   76   24.610   40.413   15.931   1.00   60.95   C       ATOM   1799   CD1   TYR   B   76   23.314   39.923   16.135   1.00   59.30   C       ATOM   1800   CE1   TYR   B   76   22.729   39.027   15.221   1.00   60.32   C       ATOM   1801   CZ   TYR   B   76   23.449   38.640   14.090   1.00   58.00   C       ATOM   1802   OH   TYR   B   76   22.931   37.778   13.142   1.00   58.90   O       ATOM   1803   CE2   TYR   B   76   24.721   39.138   13.879   1.00   60.57   C       ATOM   1804   CD2   TYR   B   76   25.285   40.017   14.784   1.00   54.01   C       ATOM   1805   C   TYR   B   76   26.608   39.745   18.286   1.00   63.37   C       ATOM   1806   O   TYR   B   76   27.806   39.995   18.413   1.00   62.55   O       ATOM   1807   N   GLU   B   77   26.138   38.508   18.149   1.00   59.87   N       ATOM   1808   CA   GLU   B   77   27.034   37.352   18.091   1.00   57.95   C       ATOM   1809   CB   GLU   B   77   26.501   36.220   18.980   1.00   58.47   C       ATOM   1810   C   GLU   B   77   27.268   36.895   16.648   1.00   54.89   C       ATOM   1811   O   GLU   B   77   26.396   36.283   16.024   1.00   53.41   O       ATOM   1812   N   TYR   B   78   28.445   37.217   16.117   1.00   52.94   N       ATOM   1813   CA   TYR   B   78   28.764   36.914   14.721   1.00   52.55   C       ATOM   1814   CB   TYR   B   78   29.841   37.877   14.187   1.00   53.56   C       ATOM   1815   CG   TYR   B   78   29.332   39.285   13.930   1.00   49.81   C       ATOM   1816   CD1   TYR   B   78   29.291   40.237   14.950   1.00   55.06   C       ATOM   1817   CE1   TYR   B   78   28.813   41.535   14.712   1.00   51.22   C       ATOM   1818   CZ   TYR   B   78   28.382   41.875   13.446   1.00   48.74   C       ATOM   1819   OH   TYR   B   78   27.919   43.147   13.187   1.00   53.04   O       ATOM   1820   CE2   TYR   B   78   28.427   40.953   12.419   1.00   46.58   C       ATOM   1821   CD2   TYR   B   78   28.904   39.670   12.660   1.00   51.58   C       ATOM   1822   C   TYR   B   78   29.184   35.451   14.537   1.00   55.29   C       ATOM   1823   O   TYR   B   78   30.229   35.031   15.035   1.00   55.26   O       ATOM   1824   N   TYR   B   79   28.352   34.674   13.835   1.00   54.89   N       ATOM   1825   CA   TYR   B   79   28.705   33.305   13.441   1.00   52.92   C       ATOM   1826   CB   TYR   B   79   27.939   32.276   14.265   1.00   53.97   C       ATOM   1827   CG   TYR   B   79   27.973   32.471   15.754   1.00   55.14   C       ATOM   1828   CD1   TYR   B   79   26.875   33.015   16.422   1.00   55.96   C       ATOM   1829   CE1   TYR   B   79   26.891   33.184   17.792   1.00   58.12   C       ATOM   1830   CZ   TYR   B   79   28.014   32.806   18.514   1.00   55.57   C       ATOM   1831   OH   TYR   B   79   28.030   32.989   19.863   1.00   57.86   O       ATOM   1832   CE2   TYR   B   79   29.121   32.269   17.875   1.00   56.26   C       ATOM   1833   CD2   TYR   B   79   29.091   32.099   16.501   1.00   53.27   C       ATOM   1834   C   TYR   B   79   28.420   32.995   11.981   1.00   54.07   C       ATOM   1835   O   TYR   B   79   27.498   33.556   11.392   1.00   52.83   O       ATOM   1836   N   LYS   B   80   29.220   32.085   11.415   1.00   53.13   N       ATOM   1837   CA   LYS   B   80   28.866   31.360   10.191   1.00   52.07   C       ATOM   1838   CB   LYS   B   80   29.990   31.406   9.149   1.00   51.71   C       ATOM   1839   CG   LYS   B   80   30.016   32.654   8.280   1.00   56.46   C       ATOM   1840   CD   LYS   B   80   31.021   32.499   7.152   1.00   55.08   C       ATOM   1841   CE   LYS   B   80   30.814   33.552   6.082   1.00   59.80   C       ATOM   1842   NZ   LYS   B   80   30.966   34.942   6.603   1.00   62.51   N       ATOM   1843   C   LYS   B   80   28.605   29.907   10.582   1.00   51.02   C       ATOM   1844   O   LYS   B   80   29.467   29.247   11.169   1.00   49.01   O       ATOM   1845   N   VAL   B   81   27.425   29.402   10.255   1.00   48.00   N       ATOM   1846   CA   VAL   B   81   27.048   28.066   10.703   1.00   48.41   C       ATOM   1847   CB   VAL   B   81   25.668   28.073   11.413   1.00   45.24   C       ATOM   1848   CG1   VAL   B   81   25.360   26.732   12.037   1.00   49.15   C       ATOM   1849   CG2   VAL   B   81   25.649   29.118   12.482   1.00   46.44   C       ATOM   1850   C   VAL   B   81   27.101   27.130   9.509   1.00   50.06   C       ATOM   1851   O   VAL   B   81   26.679   27.501   8.411   1.00   50.73   O       ATOM   1852   N   TYR   B   82   27.620   25.923   9.722   1.00   50.39   N       ATOM   1853   CA   TYR   B   82   27.909   24.998   8.622   1.00   51.80   C       ATOM   1854   CB   TYR   B   82   29.422   24.860   8.414   1.00   50.05   C       ATOM   1855   CG   TYR   B   82   30.088   26.033   7.741   1.00   55.29   C       ATOM   1856   CD1   TYR   B   82   30.609   27.094   8.492   1.00   60.37   C       ATOM   1857   CE1   TYR   B   82   31.237   28.183   7.871   1.00   59.32   C       ATOM   1858   CZ   TYR   B   82   31.357   28.209   6.486   1.00   60.82   C       ATOM   1859   OH   TYR   B   82   31.973   29.283   5.860   1.00   56.78   O       ATOM   1860   CE2   TYR   B   82   30.862   27.153   5.726   1.00   60.90   C       ATOM   1861   CD2   TYR   B   82   30.221   26.079   6.361   1.00   56.29   C       ATOM   1862   C   TYR   B   82   27.352   23.617   8.889   1.00   51.81   C       ATOM   1863   O   TYR   B   82   27.264   23.196   10.039   1.00   52.65   O       ATOM   1864   N   MET   B   83   26.999   22.916   7.815   1.00   52.67   N       ATOM   1865   CA   MET   B   83   26.743   21.484   7.884   1.00   54.74   C       ATOM   1866   CB   MET   B   83   25.601   21.099   6.941   1.00   55.19   C       ATOM   1867   CG   MET   B   83   25.406   19.614   6.751   1.00   55.78   C       ATOM   1868   SD   MET   B   83   24.629   18.846   8.168   1.00   62.13   S       ATOM   1869   CE   MET   B   83   22.912   18.982   7.717   1.00   53.46   C       ATOM   1870   C   MET   B   83   28.047   20.750   7.522   1.00   55.00   C       ATOM   1871   O   MET   B   83   28.531   20.846   6.387   1.00   53.90   O       ATOM   1872   N   VAL   B   84   28.621   20.054   8.505   1.00   55.21   N       ATOM   1873   CA   VAL   B   84   29.917   19.375   8.347   1.00   52.74   C       ATOM   1874   CB   VAL   B   84   30.977   19.860   9.389   1.00   50.47   C       ATOM   1875   CG1   VAL   B   84   31.411   21.268   9.096   1.00   46.44   C       ATOM   1876   CG2   VAL   B   84   30.466   19.738   10.816   1.00   49.60   C       ATOM   1877   C   VAL   B   84   29.801   17.856   8.434   1.00   55.22   C       ATOM   1878   O   VAL   B   84   28.712   17.308   8.613   1.00   55.27   O       ATOM   1879   N   ASP   B   85   30.946   17.194   8.289   1.00   57.58   N       ATOM   1880   CA   ASP   B   85   31.090   15.759   8.523   1.00   59.75   C       ATOM   1881   CB   ASP   B   85   32.035   15.146   7.471   1.00   61.05   C       ATOM   1882   CG   ASP   B   85   33.409   15.825   7.436   1.00   65.18   C       ATOM   1883   OD1   ASP   B   85   33.598   16.760   6.623   1.00   67.19   O       ATOM   1884   OD2   ASP   B   85   34.298   15.421   8.224   1.00   68.81   O       ATOM   1885   C   ASP   B   85   31.603   15.485   9.949   1.00   57.67   C       ATOM   1886   O   ASP   B   85   32.138   16.374   10.606   1.00   59.66   O       ATOM   1887   N   LYS   B   86   31.433   14.256   10.423   1.00   57.11   N       ATOM   1888   CA   LYS   B   86   31.936   13.859   11.738   1.00   54.53   C       ATOM   1889   CB   LYS   B   86   31.798   12.349   11.916   1.00   52.85   C       ATOM   1890   CG   LYS   B   86   32.434   11.817   13.179   1.00   44.47   C       ATOM   1891   CD   LYS   B   86   32.959   10.389   12.950   1.00   41.89   C       ATOM   1892   CE   LYS   B   86   32.765   9.541   14.174   1.00   38.48   C       ATOM   1893   NZ   LYS   B   86   33.495   10.036   15.379   1.00   47.23   N       ATOM   1894   C   LYS   B   86   33.389   14.294   12.000   1.00   55.95   C       ATOM   1895   O   LYS   B   86   33.713   14.762   13.093   1.00   55.26   O       ATOM   1896   N   ASP   B   87   34.253   14.147   10.999   1.00   57.71   N       ATOM   1897   CA   ASP   B   87   35.673   14.480   11.149   1.00   60.04   C       ATOM   1898   CB   ASP   B   87   36.528   13.745   10.107   1.00   59.81   C       ATOM   1899   CG   ASP   B   87   37.035   12.406   10.606   1.00   64.01   C       ATOM   1900   OD1   ASP   B   87   37.633   12.362   11.709   1.00   62.33   O       ATOM   1901   OD2   ASP   B   87   36.847   11.399   9.882   1.00   62.56   O       ATOM   1902   C   ASP   B   87   35.941   15.980   11.078   1.00   60.97   C       ATOM   1903   O   ASP   B   87   36.953   16.449   11.581   1.00   61.10   O       ATOM   1904   N   GLN   B   88   35.057   16.738   10.446   1.00   61.32   N       ATOM   1905   CA   GLN   B   88   35.265   18.178   10.363   1.00   63.39   C       ATOM   1906   CB   GLN   B   88   34.473   18.784   9.208   1.00   63.94   C       ATOM   1907   C   GLN   B   88   34.837   18.810   11.667   1.00   64.84   C       ATOM   1908   O   GLN   B   88   35.222   19.929   11.983   1.00   65.42   O       ATOM   1909   N   ALA   B   89   34.040   18.061   12.417   1.00   65.49   N       ATOM   1910   CA   ALA   B   89   33.424   18.533   13.644   1.00   65.15   C       ATOM   1911   CB   ALA   B   89   31.989   18.034   13.731   1.00   65.66   C       ATOM   1912   C   ALA   B   89   34.212   18.022   14.824   1.00   64.18   C       ATOM   1913   O   ALA   B   89   34.544   18.765   15.735   1.00   63.09   O       ATOM   1914   O   ASP   B   90   36.855   17.048   17.406   1.00   20.00   O       ATOM   1915   N   ASP   B   90   34.503   16.731   14.795   1.00   20.00   N       ATOM   1916   CA   ASP   B   90   35.305   16.114   15.829   1.00   20.00   C       ATOM   1917   C   ASP   B   90   36.371   17.098   16.280   1.00   20.00   C       ATOM   1918   CB   ASP   B   90   35.928   14.827   15.303   1.00   20.00   C       ATOM   1919   CG   ASP   B   90   35.238   13.602   15.839   1.00   20.00   C       ATOM   1920   OD1   ASP   B   90   34.100   13.741   16.329   1.00   20.00   O       ATOM   1921   OD2   ASP   B   90   35.838   12.510   15.788   1.00   20.00   O       ATOM   1922   O   ARG   B   91   38.909   20.743   14.930   1.00   20.00   O       ATOM   1923   N   ARG   B   91   36.693   18.021   15.390   1.00   20.00   N       ATOM   1924   CA   ARG   B   91   38.029   18.543   15.278   1.00   20.00   C       ATOM   1925   C   ARG   B   91   37.934   19.999   14.865   1.00   20.00   C       ATOM   1926   CB   ARG   B   91   38.794   17.757   14.225   1.00   20.00   C       ATOM   1927   N   CYS   B   92   36.744   20.402   14.436   1.00   65.62   N       ATOM   1928   CA   CYS   B   92   36.377   21.803   14.449   1.00   63.54   C       ATOM   1929   CB   CYS   B   92   36.658   22.414   15.813   1.00   62.30   C       ATOM   1930   SG   CYS   B   92   35.415   22.029   17.030   1.00   61.91   S       ATOM   1931   C   CYS   B   92   37.103   22.560   13.364   1.00   63.64   C       ATOM   1932   O   CYS   B   92   37.751   23.557   13.622   1.00   62.94   O       ATOM   1933   N   THR   B   93   36.973   22.076   12.139   1.00   66.00   N       ATOM   1934   CA   THR   B   93   37.644   22.682   10.998   1.00   69.32   C       ATOM   1935   CB   THR   B   93   38.992   21.965   10.653   1.00   69.46   C       ATOM   1936   OG1   THR   B   93   39.501   22.457   9.406   1.00   71.08   O       ATOM   1937   CG2   THR   B   93   38.813   20.447   10.563   1.00   67.96   C       ATOM   1938   C   THR   B   93   36.711   22.682   9.798   1.00   70.96   C       ATOM   1939   O   THR   B   93   36.174   21.638   9.422   1.00   72.14   O       ATOM   1940   N   ILE   B   94   36.500   23.868   9.231   1.00   72.37   N       ATOM   1941   CA   ILE   B   94   35.749   24.019   7.985   1.00   73.47   C       ATOM   1942   CB   ILE   B   94   34.519   24.973   8.129   1.00   72.37   C       ATOM   1943   CG1   ILE   B   94   34.943   26.416   8.425   1.00   71.50   C       ATOM   1944   CD1   ILE   B   94   34.846   27.339   7.244   1.00   65.08   C       ATOM   1945   CG2   ILE   B   94   33.571   24.464   9.211   1.00   72.82   C       ATOM   1946   C   ILE   B   94   36.699   24.430   6.851   1.00   74.87   C       ATOM   1947   O   ILE   B   94   36.281   24.598   5.701   1.00   74.36   O       ATOM   1948   N   LYS   B   95   37.979   24.587   7.201   1.00   76.69   N       ATOM   1949   CA   LYS   B   95   39.050   24.828   6.236   1.00   78.11   C       ATOM   1950   CB   LYS   B   95   40.345   25.209   6.955   1.00   77.98   C       ATOM   1951   C   LYS   B   95   39.231   23.555   5.414   1.00   79.85   C       ATOM   1952   O   LYS   B   95   40.318   22.964   5.359   1.00   80.52   O       ATOM   1953   N   LYS   B   96   38.132   23.164   4.770   1.00   80.67   N       ATOM   1954   CA   LYS   B   96   37.946   21.878   4.109   1.00   80.88   C       ATOM   1955   CB   LYS   B   96   38.263   20.732   5.106   1.00   80.35   C       ATOM   1956   CG   LYS   B   96   37.430   19.457   5.056   1.00   79.50   C       ATOM   1957   CD   LYS   B   96   36.505   19.334   6.265   1.00   77.17   C       ATOM   1958   CE   LYS   B   96   35.924   20.675   6.665   1.00   77.09   C       ATOM   1959   NZ   LYS   B   96   34.524   20.596   7.133   1.00   76.80   N       ATOM   1960   C   LYS   B   96   36.494   21.937   3.589   1.00   81.93   C       ATOM   1961   O   LYS   B   96   35.881   23.011   3.640   1.00   82.40   O       ATOM   1962   N   GLU   B   97   35.953   20.832   3.071   1.00   82.44   N       ATOM   1963   CA   GLU   B   97   34.574   20.804   2.541   1.00   82.95   C       ATOM   1964   CB   GLU   B   97   34.245   19.415   1.978   1.00   82.71   C       ATOM   1965   C   GLU   B   97   33.513   21.250   3.575   1.00   82.95   C       ATOM   1966   O   GLU   B   97   33.406   20.664   4.663   1.00   83.36   O       ATOM   1967   N   ASN   B   98   32.746   22.291   3.233   1.00   81.59   N       ATOM   1968   CA   ASN   B   98   31.794   22.911   4.171   1.00   79.66   C       ATOM   1969   CB   ASN   B   98   32.549   23.709   5.239   1.00   80.02   C       ATOM   1970   C   ASN   B   98   30.731   23.801   3.511   1.00   78.31   C       ATOM   1971   O   ASN   B   98   31.048   24.644   2.660   1.00   77.79   O       ATOM   1972   N   THR   B   99   29.478   23.620   3.932   1.00   76.30   N       ATOM   1973   CA   THR   B   99   28.321   24.312   3.327   1.00   74.52   C       ATOM   1974   CB   THR   B   99   27.334   23.301   2.663   1.00   74.67   C       ATOM   1975   OG1   THR   B   99   27.823   21.957   2.811   1.00   73.98   O       ATOM   1976   CG2   THR   B   99   27.139   23.624   1.182   1.00   73.78   C       ATOM   1977   C   THR   B   99   27.570   25.185   4.363   1.00   72.17   C       ATOM   1978   O   THR   B   99   26.920   24.645   5.274   1.00   72.60   O       ATOM   1979   N   PRO   B   100   27.641   26.530   4.214   1.00   68.26   N       ATOM   1980   CA   PRO   B   100   27.251   27.464   5.286   1.00   65.84   C       ATOM   1981   CB   PRO   B   100   28.052   28.743   4.960   1.00   65.48   C       ATOM   1982   CG   PRO   B   100   28.612   28.545   3.556   1.00   66.33   C       ATOM   1983   CD   PRO   B   100   28.070   27.252   3.005   1.00   68.07   C       ATOM   1984   C   PRO   B   100   25.752   27.753   5.352   1.00   62.59   C       ATOM   1985   O   PRO   B   100   25.240   28.596   4.605   1.00   63.79   O       ATOM   1986   N   LEU   B   101   25.071   27.056   6.259   1.00   59.41   N       ATOM   1987   CA   LEU   B   101   23.617   27.127   6.403   1.00   56.35   C       ATOM   1988   CB   LEU   B   101   23.105   25.985   7.290   1.00   56.25   C       ATOM   1989   CG   LEU   B   101   23.449   24.556   6.871   1.00   53.36   C       ATOM   1990   CD1   LEU   B   101   22.629   23.566   7.659   1.00   57.33   C       ATOM   1991   CD2   LEU   B   101   23.255   24.344   5.374   1.00   48.21   C       ATOM   1992   C   LEU   B   101   23.126   28.455   6.951   1.00   56.12   C       ATOM   1993   O   LEU   B   101   22.025   28.905   6.620   1.00   55.96   O       ATOM   1994   N   LEU   B   102   23.923   29.074   7.812   1.00   54.26   N       ATOM   1995   CA   LEU   B   102   23.641   30.435   8.253   1.00   52.03   C       ATOM   1996   CB   LEU   B   102   23.173   30.459   9.708   1.00   52.13   C       ATOM   1997   CG   LEU   B   102   21.954   29.702   10.235   1.00   50.45   C       ATOM   1998   CD1   LEU   B   102   22.041   29.695   11.719   1.00   55.04   C       ATOM   1999   CD2   LEU   B   102   20.692   30.392   9.827   1.00   60.55   C       ATOM   2000   C   LEU   B   102   24.870   31.323   8.140   1.00   52.59   C       ATOM   2001   O   LEU   B   102   25.984   30.933   8.523   1.00   51.55   O       ATOM   2002   N   ASN   B   103   24.655   32.521   7.621   1.00   53.64   N       ATOM   2003   CA   ASN   B   103   25.600   33.615   7.793   1.00   54.00   C       ATOM   2004   CB   ASN   B   103   25.998   34.252   6.467   1.00   54.78   C       ATOM   2005   CG   ASN   B   103   26.931   35.436   6.665   1.00   58.33   C       ATOM   2006   OD1   ASN   B   103   28.084   35.271   7.084   1.00   58.48   O       ATOM   2007   ND2   ASN   B   103   26.424   36.643   6.399   1.00   45.80   N       ATOM   2008   C   ASN   B   103   25.015   34.670   8.720   1.00   53.18   C       ATOM   2009   O   ASN   B   103   24.442   35.657   8.267   1.00   54.82   O       ATOM   2010   N   CYS   B   104   25.172   34.463   10.023   1.00   52.46   N       ATOM   2011   CA   CYS   B   104   24.649   35.394   11.007   1.00   51.44   C       ATOM   2012   CB   CYS   B   104   24.466   34.700   12.341   1.00   53.41   C       ATOM   2013   SG   CYS   B   104   23.832   33.036   12.178   1.00   49.61   S       ATOM   2014   C   CYS   B   104   25.604   36.556   11.139   1.00   53.20   C       ATOM   2015   O   CYS   B   104   26.565   36.513   11.915   1.00   51.74   O       ATOM   2016   N   ALA   B   105   25.335   37.578   10.338   1.00   52.80   N       ATOM   2017   CA   ALA   B   105   26.121   38.783   10.298   1.00   52.86   C       ATOM   2018   CB   ALA   B   105   27.202   38.669   9.219   1.00   53.20   C       ATOM   2019   C   ALA   B   105   25.188   39.945   10.006   1.00   53.19   C       ATOM   2020   O   ALA   B   105   25.501   40.812   9.184   1.00   54.31   O       ATOM   2021   N   ARG   B   106   24.030   39.929   10.668   1.00   54.23   N       ATOM   2022   CA   ARG   B   106   23.018   40.988   10.559   1.00   53.54   C       ATOM   2023   CB   ARG   B   106   21.984   40.637   9.480   1.00   53.56   C       ATOM   2024   C   ARG   B   106   22.319   41.211   11.900   1.00   53.50   C       ATOM   2025   O   ARG   B   106   21.322   40.545   12.206   1.00   53.50   O       ATOM   2026   N   PRO   B   107   22.847   42.136   12.715   1.00   53.15   N       ATOM   2027   CA   PRO   B   107   22.255   42.466   14.024   1.00   54.11   C       ATOM   2028   CB   PRO   B   107   23.089   43.666   14.488   1.00   55.59   C       ATOM   2029   CG   PRO   B   107   24.428   43.483   13.797   1.00   51.19   C       ATOM   2030   CD   PRO   B   107   24.091   42.894   12.459   1.00   52.06   C       ATOM   2031   C   PRO   B   107   20.745   42.804   14.041   1.00   56.24   C       ATOM   2032   O   PRO   B   107   20.048   42.480   15.012   1.00   57.46   O       ATOM   2033   N   ASP   B   108   20.245   43.423   12.978   1.00   56.84   N       ATOM   2034   CA   ASP   B   108   18.905   44.009   13.004   1.00   56.83   C       ATOM   2035   CB   ASP   B   108   18.933   45.389   12.354   1.00   58.06   C       ATOM   2036   CG   ASP   B   108   17.754   46.242   12.761   1.00   60.68   C       ATOM   2037   OD1   ASP   B   108   17.196   46.004   13.857   1.00   64.10   O       ATOM   2038   OD2   ASP   B   108   17.386   47.154   11.988   1.00   66.86   O       ATOM   2039   C   ASP   B   108   17.823   43.138   12.362   1.00   56.19   C       ATOM   2040   O   ASP   B   108   16.689   43.573   12.151   1.00   53.32   O       ATOM   2041   N   GLN   B   109   18.170   41.887   12.085   1.00   56.39   N       ATOM   2042   CA   GLN   B   109   17.298   41.022   11.324   1.00   55.55   C       ATOM   2043   CB   GLN   B   109   17.632   41.124   9.827   1.00   55.41   C       ATOM   2044   CG   GLN   B   109   17.483   39.837   9.023   1.00   58.46   C       ATOM   2045   CD   GLN   B   109   17.142   40.063   7.561   1.00   61.57   C       ATOM   2046   OE1   GLN   B   109   17.045   41.204   7.089   1.00   66.19   O       ATOM   2047   NE2   GLN   B   109   16.949   38.971   6.831   1.00   64.69   N       ATOM   2048   C   GLN   B   109   17.368   39.593   11.852   1.00   57.37   C       ATOM   2049   O   GLN   B   109   18.452   39.029   12.060   1.00   57.65   O       ATOM   2050   N   ASP   B   110   16.192   39.038   12.100   1.00   56.55   N       ATOM   2051   CA   ASP   B   110   16.039   37.669   12.534   1.00   57.00   C       ATOM   2052   CB   ASP   B   110   14.552   37.452   12.871   1.00   58.93   C       ATOM   2053   CG   ASP   B   110   14.329   36.698   14.179   1.00   61.20   C       ATOM   2054   OD1   ASP   B   110   15.110   36.866   15.149   1.00   64.56   O       ATOM   2055   OD2   ASP   B   110   13.335   35.946   14.236   1.00   62.44   O       ATOM   2056   C   ASP   B   110   16.481   36.773   11.360   1.00   55.17   C       ATOM   2057   O   ASP   B   110   15.835   36.771   10.316   1.00   56.87   O       ATOM   2058   N   VAL   B   111   17.581   36.039   11.523   1.00   51.13   N       ATOM   2059   CA   VAL   B   111   18.119   35.158   10.471   1.00   47.12   C       ATOM   2060   CB   VAL   B   111   19.647   35.389   10.217   1.00   48.87   C       ATOM   2061   CG1   VAL   B   111   20.219   34.352   9.227   1.00   53.14   C       ATOM   2062   CG2   VAL   B   111   19.938   36.818   9.728   1.00   42.07   C       ATOM   2063   C   VAL   B   111   17.921   33.693   10.852   1.00   46.36   C       ATOM   2064   O   VAL   B   111   18.266   33.289   11.975   1.00   42.74   O       ATOM   2065   N   LYS   B   112   17.400   32.898   9.915   1.00   43.12   N       ATOM   2066   CA   LYS   B   112   17.032   31.485   10.162   1.00   43.58   C       ATOM   2067   CB   LYS   B   112   15.546   31.455   10.558   1.00   42.82   C       ATOM   2068   CG   LYS   B   112   14.766   30.199   10.270   1.00   44.74   C       ATOM   2069   CD   LYS   B   112   13.271   30.542   10.259   1.00   48.96   C       ATOM   2070   CE   LYS   B   112   12.691   30.498   11.670   1.00   45.37   C       ATOM   2071   NZ   LYS   B   112   11.754   31.661   11.947   1.00   45.29   N       ATOM   2072   C   LYS   B   112   17.346   30.504   9.003   1.00   42.43   C       ATOM   2073   O   LYS   B   112   17.477   30.921   7.847   1.00   45.59   O       ATOM   2074   N   PHE   B   113   17.513   29.216   9.327   1.00   40.79   N       ATOM   2075   CA   PHE   B   113   17.572   28.148   8.331   1.00   38.79   C       ATOM   2076   CB   PHE   B   113   18.998   27.550   8.153   1.00   39.14   C       ATOM   2077   CG   PHE   B   113   19.104   26.543   6.997   1.00   34.85   C       ATOM   2078   CD1   PHE   B   113   19.549   26.945   5.741   1.00   35.55   C       ATOM   2079   CE1   PHE   B   113   19.640   26.015   4.697   1.00   38.24   C       ATOM   2080   CZ   PHE   B   113   19.250   24.709   4.892   1.00   34.91   C       ATOM   2081   CE2   PHE   B   113   18.807   24.299   6.148   1.00   40.75   C       ATOM   2082   CD2   PHE   B   113   18.737   25.208   7.177   1.00   44.17   C       ATOM   2083   C   PHE   B   113   16.634   27.073   8.800   1.00   39.23   C       ATOM   2084   O   PHE   B   113   16.731   26.593   9.956   1.00   43.15   O       ATOM   2085   N   THR   B   114   15.728   26.686   7.916   1.00   36.48   N       ATOM   2086   CA   THR   B   114   14.768   25.619   8.184   1.00   36.83   C       ATOM   2087   CB   THR   B   114   13.384   25.985   7.687   1.00   40.83   C       ATOM   2088   OG1   THR   B   114   12.968   27.231   8.286   1.00   37.54   O       ATOM   2089   CG2   THR   B   114   12.394   24.877   7.993   1.00   36.72   C       ATOM   2090   C   THR   B   114   15.214   24.313   7.502   1.00   38.84   C       ATOM   2091   O   THR   B   114   15.307   24.201   6.286   1.00   40.09   O       ATOM   2092   N   ILE   B   115   15.501   23.317   8.311   1.00   38.37   N       ATOM   2093   CA   ILE   B   115   15.934   22.042   7.802   1.00   38.31   C       ATOM   2094   CB   ILE   B   115   16.914   21.365   8.790   1.00   38.74   C       ATOM   2095   OG1   ILE   B   115   18.233   22.145   8.874   1.00   40.45   C       ATOM   2096   CD1   ILE   B   115   19.179   21.628   9.988   1.00   41.07   C       ATOM   2097   CG2   ILE   B   115   17.189   19.957   8.376   1.00   37.17   C       ATOM   2098   C   ILE   B   115   14.696   21.197   7.693   1.00   39.26   C       ATOM   2099   O   ILE   B   115   13.905   21.146   8.626   1.00   40.19   O       ATOM   2100   N   LYS   B   116   14.508   20.566   6.539   1.00   38.88   N       ATOM   2101   CA   LYS   B   116   13.586   19.455   6.452   1.00   39.98   C       ATOM   2102   CB   LYS   B   116   12.647   19.601   5.253   1.00   39.37   C       ATOM   2103   CG   LYS   B   116   11.972   18.305   4.805   1.00   40.21   C       ATOM   2104   CD   LYS   B   116   10.761   18.025   5.630   1.00   40.79   C       ATOM   2105   CE   LYS   B   116   9.630   17.361   4.844   1.00   47.35   C       ATOM   2106   NZ   LYS   B   116   10.037   16.252   3.926   1.00   43.81   N       ATOM   2107   C   LYS   B   116   14.408   18.162   6.350   1.00   41.05   C       ATOM   2108   O   LYS   B   116   15.163   17.961   5.393   1.00   40.58   O       ATOM   2109   N   PHE   B   117   14.250   17.299   7.347   1.00   40.29   N       ATOM   2110   CA   PHE   B   117   14.894   15.997   7.368   1.00   40.81   C       ATOM   2111   CB   PHE   B   117   14.958   15.425   8.801   1.00   41.73   C       ATOM   2112   CG   PHE   B   117   15.737   16.291   9.761   1.00   39.87   C       ATOM   2113   CD1   PHE   B   117   15.091   17.297   10.487   1.00   40.27   C       ATOM   2114   CE1   PHE   B   117   15.791   18.118   11.354   1.00   36.48   C       ATOM   2115   CZ   PHE   B   117   17.174   17.971   11.468   1.00   40.12   C       ATOM   2116   CE2   PHE   B   117   17.845   16.976   10.706   1.00   36.80   C       ATOM   2117   CD2   PHE   B   117   17.121   16.151   9.874   1.00   34.89   C       ATOM   2118   C   PHE   B   117   14.109   15.078   6.451   1.00   42.46   C       ATOM   2119   O   PHE   B   117   13.074   14.534   6.839   1.00   42.34   O       ATOM   2120   N   GLN   B   118   14.599   14.956   5.220   1.00   43.34   N       ATOM   2121   CA   GLN   B   118   14.001   14.143   4.168   1.00   42.93   C       ATOM   2122   CB   GLN   B   118   13.223   15.038   3.177   1.00   47.34   C       ATOM   2123   CG   GLN   B   118   14.085   16.077   2.491   1.00   34.74   C       ATOM   2124   CD   GLN   B   118   13.336   16.995   1.531   1.00   41.59   C       ATOM   2125   OE1   GLN   B   118   13.710   18.137   1.385   1.00   41.26   O       ATOM   2126   NE2   GLN   B   118   12.277   16.508   0.896   1.00   37.39   N       ATOM   2127   C   GLN   B   118   15.137   13.401   3.453   1.00   43.86   C       ATOM   2128   O   GLN   B   118   16.281   13.882   3.422   1.00   40.85   O       ATOM   2129   N   GLU   B   119   14.817   12.239   2.873   1.00   45.99   N       ATOM   2130   CA   GLU   B   119   15.833   11.342   2.277   1.00   46.54   C       ATOM   2131   CB   GLU   B   119   15.266   9.924   2.128   1.00   49.19   C       ATOM   2132   CG   GLU   B   119   16.253   8.817   2.513   1.00   54.11   C       ATOM   2133   CD   GLU   B   119   15.932   8.188   3.859   1.00   62.40   C       ATOM   2134   OE1   GLU   B   119   14.732   8.144   4.211   1.00   69.97   O       ATOM   2135   OE2   GLU   B   119   16.864   7.725   4.560   1.00   62.46   O       ATOM   2136   C   GLU   B   119   16.375   11.802   0.913   1.00   45.75   C       ATOM   2137   O   GLU   B   119   17.486   11.447   0.523   1.00   46.08   O       ATOM   2138   N   PHE   B   120   15.579   12.606   0.212   1.00   41.97   N       ATOM   2139   CA   PHE   B   120   15.842   13.014   −1.161   1.00   41.19   C       ATOM   2140   CB   PHE   B   120   15.190   11.988   −2.102   1.00   41.38   C       ATOM   2141   CG   PHE   B   120   15.342   12.284   −3.568   1.00   44.79   C       ATOM   2142   CD1   PHE   B   120   16.433   11.791   −4.276   1.00   46.25   C       ATOM   2143   CE1   PHE   B   120   16.573   12.041   −5.639   1.00   48.01   C       ATOM   2144   CZ   PHE   B   120   15.597   12.780   −6.311   1.00   48.10   C       ATOM   2145   CE2   PHE   B   120   14.491   13.269   −5.614   1.00   48.86   C       ATOM   2146   CD2   PHE   B   120   14.363   13.008   −4.251   1.00   47.10   C       ATOM   2147   C   PHE   B   120   15.235   14.411   −1.339   1.00   38.45   C       ATOM   2148   O   PHE   B   120   14.098   14.642   −0.939   1.00   39.71   O       ATOM   2149   N   SER   B   121   16.001   15.338   −1.908   1.00   38.75   N       ATOM   2150   CA   SER   B   121   15.503   16.687   −2.222   1.00   35.73   C       ATOM   2151   CB   SER   B   121   16.336   17.720   −1.482   1.00   41.04   C       ATOM   2152   OG   SER   B   121   16.075   19.038   −1.979   1.00   32.57   O       ATOM   2153   C   SER   B   121   15.630   16.928   −3.713   1.00   36.73   C       ATOM   2154   O   SER   B   121   16.697   16.644   −4.245   1.00   37.53   O       ATOM   2155   N   PRO   B   122   14.549   17.421   −4.414   1.00   35.00   N       ATOM   2156   CA   PRO   B   122   14.686   17.884   −5.794   1.00   31.41   C       ATOM   2157   CB   PRO   B   122   13.251   18.193   −6.211   1.00   33.87   C       ATOM   2158   CG   PRO   B   122   12.549   18.466   −4.956   1.00   36.13   C       ATOM   2159   CD   PRO   B   122   13.128   17.460   −4.018   1.00   31.71   C       ATOM   2160   C   PRO   B   122   15.605   19.080   −6.037   1.00   34.20   C       ATOM   2161   O   PRO   B   122   15.924   19.376   −7.206   1.00   28.62   O       ATOM   2162   N   ASN   B   123   16.063   19.713   −4.952   1.00   35.06   N       ATOM   2163   CA   ASN   B   123   17.077   20.740   −5.053   1.00   35.87   C       ATOM   2164   CB   ASN   B   123   17.094   21.655   −3.821   1.00   36.31   C       ATOM   2165   CG   ASN   B   123   18.043   22.880   −3.984   1.00   33.87   C       ATOM   2166   OD1   ASN   B   123   18.656   23.093   −5.032   1.00   32.22   O       ATOM   2167   ND2   ASN   B   123   18.121   23.693   −2.943   1.00   35.68   N       ATOM   2168   C   ASN   B   123   18.448   20.112   −5.270   1.00   34.15   C       ATOM   2169   O   ASN   B   123   18.928   19.291   −4.469   1.00   33.65   O       ATOM   2170   N   LEU   B   124   19.039   20.510   −6.383   1.00   33.29   N       ATOM   2171   CA   LEU   B   124   20.394   20.196   −6.723   1.00   37.26   C       ATOM   2172   CB   LEU   B   124   20.804   21.083   −7.895   1.00   35.44   C       ATOM   2173   CG   LEU   B   124   22.203   20.963   −8.484   1.00   40.34   C       ATOM   2174   CD1   LEU   B   124   22.338   19.636   −9.207   1.00   35.24   C       ATOM   2175   CD2   LEU   B   124   22.360   22.114   −9.433   1.00   38.11   C       ATOM   2176   C   LEU   B   124   21.341   20.364   −5.524   1.00   36.68   C       ATOM   2177   O   LEU   B   124   22.267   19.587   −5.378   1.00   38.26   O       ATOM   2178   N   TRP   B   125   21.088   21.354   −4.662   1.00   37.81   N       ATOM   2179   CA   TRP   B   125   21.878   21.556   −3.442   1.00   41.99   C       ATOM   2180   CB   TRP   B   125   22.371   22.993   −3.331   1.00   44.52   C       ATOM   2181   CG   TRP   B   125   23.266   23.394   −4.426   1.00   48.30   C       ATOM   2182   CD1   TRP   B   125   24.609   23.183   −4.507   1.00   48.48   C       ATOM   2183   NE1   TRP   B   125   25.100   23.701   −5.680   1.00   46.89   N       ATOM   2184   CE2   TRP   B   125   24.065   24.261   −6.381   1.00   48.31   C       ATOM   2185   CD2   TRP   B   125   22.892   24.093   −5.611   1.00   48.46   C       ATOM   2186   CE3   TRP   B   125   21.675   24.579   −6.110   1.00   51.01   C       ATOM   2187   CZ3   TRP   B   125   21.674   25.222   −7.336   1.00   47.38   C       ATOM   2188   CH2   TRP   B   125   22.857   25.380   −8.074   1.00   47.99   C       ATOM   2189   CZ2   TRP   B   125   24.062   24.917   −7.611   1.00   47.47   C       ATOM   2190   C   TRP   B   125   21.117   21.240   −2.181   1.00   41.23   C       ATOM   2191   O   TRP   B   125   21.540   21.611   −1.091   1.00   44.51   O       ATOM   2192   N   GLY   B   126   20.007   20.538   −2.321   1.00   40.47   N       ATOM   2193   CA   GLY   B   126   19.175   20.183   −1.183   1.00   40.35   C       ATOM   2194   C   GLY   B   126   19.900   19.357   −0.144   1.00   41.68   C       ATOM   2195   O   GLY   B   126   20.904   18.705   −0.452   1.00   41.73   O       ATOM   2196   N   LEU   B   127   19.384   19.378   1.086   1.00   41.78   N       ATOM   2197   CA   LEU   B   127   19.928   18.578   2.187   1.00   43.54   C       ATOM   2198   CB   LEU   B   127   19.885   19.371   3.502   1.00   45.56   C       ATOM   2199   CG   LEU   B   127   20.829   20.562   3.715   1.00   45.47   C       ATOM   2200   CD1   LEU   B   127   20.761   21.056   5.145   1.00   47.06   C       ATOM   2201   CD2   LEU   B   127   22.269   20.227   3.361   1.00   52.41   C       ATOM   2202   C   LEU   B   127   19.169   17.251   2.317   1.00   46.47   C       ATOM   2203   O   LEU   B   127   17.932   17.223   2.246   1.00   45.51   O       ATOM   2204   N   GLU   B   128   19.914   16.151   2.486   1.00   49.01   N       ATOM   2205   CA   GLU   B   128   19.358   14.785   2.392   1.00   50.26   C       ATOM   2206   CB   GLU   B   128   19.662   14.201   1.002   1.00   50.78   C       ATOM   2207   CG   GLU   B   128   19.339   15.167   −0.175   1.00   52.96   C       ATOM   2208   CD   GLU   B   128   19.395   14.518   −1.561   1.00   52.08   C       ATOM   2209   OE1   GLU   B   128   20.089   13.484   −1.727   1.00   54.11   O       ATOM   2210   OE2   GLU   B   128   18.733   15.050   −2.500   1.00   44.98   O       ATOM   2211   C   GLU   B   128   19.870   13.866   3.541   1.00   51.60   C       ATOM   2212   O   GLU   B   128   21.053   13.901   3.882   1.00   51.94   O       ATOM   2213   N   PHE   B   129   18.984   13.064   4.143   1.00   50.16   N       ATOM   2214   CA   PHE   B   129   19.301   12.410   5.428   1.00   50.35   C       ATOM   2215   CB   PHE   B   129   18.616   13.148   6.579   1.00   49.69   C       ATOM   2216   CG   PHE   B   129   19.000   14.602   6.689   1.00   53.84   C       ATOM   2217   CD1   PHE   B   129   18.143   15.602   6.218   1.00   53.48   C       ATOM   2218   CE1   PHE   B   129   18.497   16.963   6.321   1.00   50.73   C       ATOM   2219   CZ   PHE   B   129   19.718   17.324   6.879   1.00   51.56   C       ATOM   2220   CE2   PHE   B   129   20.589   16.329   7.349   1.00   56.53   C       ATOM   2221   CD2   PHE   B   129   20.223   14.982   7.253   1.00   53.44   C       ATOM   2222   C   PHE   B   129   18.985   10.907   5.487   1.00   52.61   C       ATOM   2223   O   PHE   B   129   17.967   10.449   4.950   1.00   51.12   O       ATOM   2224   N   GLN   B   130   19.849   10.151   6.172   1.00   56.51   N       ATOM   2225   CA   GLN   B   130   19.828   8.674   6.124   1.00   59.82   C       ATOM   2226   CB   GLN   B   130   21.247   8.116   5.889   1.00   60.33   C       ATOM   2227   CG   GLN   B   130   22.020   8.753   4.713   1.00   61.86   C       ATOM   2228   CD   GLN   B   130   23.338   8.053   4.385   1.00   60.72   C       ATOM   2229   OE1   GLN   B   130   23.752   7.113   5.069   1.00   69.64   O       ATOM   2230   NE2   GLN   B   130   23.997   8.508   3.322   1.00   59.67   N       ATOM   2231   C   GLN   B   130   19.170   7.969   7.328   1.00   60.84   C       ATOM   2232   O   GLN   B   130   19.206   8.461   8.465   1.00   59.63   O       ATOM   2233   N   ALA   B   131   18.610   6.790   7.038   1.00   63.58   N       ATOM   2234   CA   ALA   B   131   17.841   5.932   7.965   1.00   64.07   C       ATOM   2235   CB   ALA   B   131   17.808   4.489   7.434   1.00   64.33   C       ATOM   2236   C   ALA   B   131   18.239   5.947   9.453   1.00   63.60   C       ATOM   2237   O   ALA   B   131   17.463   6.390   10.298   1.00   64.85   O       ATOM   2238   N   ASN   B   132   19.426   5.437   9.765   1.00   61.85   N       ATOM   2239   CA   ASN   B   132   19.939   5.450   11.134   1.00   58.11   C       ATOM   2240   CB   ASN   B   132   19.985   4.033   11.716   1.00   57.70   C       ATOM   2241   CG   ASN   B   132   19.258   3.917   13.056   1.00   57.57   C       ATOM   2242   OD1   ASN   B   132   19.863   4.027   14.125   1.00   52.75   O       ATOM   2243   ND2   ASN   B   132   17.953   3.688   12.998   1.00   56.67   N       ATOM   2244   C   ASN   B   132   21.325   6.091   11.097   1.00   56.55   C       ATOM   2245   O   ASN   B   132   22.347   5.409   11.243   1.00   54.32   O       ATOM   2246   N   LYS   B   133   21.343   7.408   10.876   1.00   52.59   N       ATOM   2247   CA   LYS   B   133   22.584   8.143   10.583   1.00   51.69   C       ATOM   2248   CB   LYS   B   133   22.726   8.277   9.055   1.00   52.35   C       ATOM   2249   CG   LYS   B   133   23.788   9.235   8.509   1.00   54.30   C       ATOM   2250   CD   LYS   B   133   25.209   8.685   8.590   1.00   55.71   C       ATOM   2251   CE   LYS   B   133   26.123   9.361   7.560   1.00   56.13   C       ATOM   2252   NZ   LYS   B   133   26.218   10.847   7.729   1.00   55.26   N       ATOM   2253   C   LYS   B   133   22.690   9.507   11.316   1.00   50.35   C       ATOM   2254   O   LYS   B   133   21.680   10.157   11.581   1.00   45.66   O       ATOM   2255   N   ASP   B   134   23.925   9.906   11.646   1.00   50.68   N       ATOM   2256   CA   ASP   B   134   24.219   11.149   12.375   1.00   51.33   C       ATOM   2257   CB   ASP   B   134   25.246   10.914   13.497   1.00   53.85   C       ATOM   2258   CG   ASP   B   134   24.881   9.760   14.403   1.00   54.97   C       ATOM   2259   OD1   ASP   B   134   23.787   9.792   15.001   1.00   61.14   O       ATOM   2260   OD2   ASP   B   134   25.692   8.818   14.521   1.00   63.22   O       ATOM   2261   C   ASP   B   134   24.781   12.214   11.446   1.00   51.63   C       ATOM   2262   O   ASP   B   134   25.579   11.910   10.546   1.00   50.16   O       ATOM   2263   N   TYR   B   135   24.368   13.464   11.678   1.00   51.47   N       ATOM   2264   CA   TYR   B   135   24.844   14.617   10.903   1.00   50.95   C       ATOM   2265   CB   TYR   B   135   23.765   15.107   9.945   1.00   51.81   C       ATOM   2266   CG   TYR   B   135   23.375   14.080   8.901   1.00   53.87   C       ATOM   2267   CD1   TYR   B   135   22.302   13.228   9.120   1.00   55.22   C       ATOM   2268   CE1   TYR   B   135   21.930   12.280   8.175   1.00   55.50   C       ATOM   2269   CZ   TYR   B   135   22.633   12.174   6.991   1.00   55.59   C       ATOM   2270   OH   TYR   B   135   22.241   11.219   6.075   1.00   55.74   O       ATOM   2271   CE2   TYR   B   135   23.716   13.008   6.738   1.00   55.39   C       ATOM   2272   CD2   TYR   B   135   24.082   13.961   7.697   1.00   50.04   C       ATOM   2273   C   TYR   B   135   25.222   15.724   11.857   1.00   50.07   C       ATOM   2274   O   TYR   B   135   24.666   15.811   12.959   1.00   47.79   O       ATOM   2275   N   TYR   B   136   26.169   16.559   11.444   1.00   52.35   N       ATOM   2276   CA   TYR   B   136   26.726   17.566   12.352   1.00   53.64   C       ATOM   2277   CB   TYR   B   136   28.187   17.242   12.691   1.00   56.73   C       ATOM   2278   CG   TYR   B   136   28.423   15.870   13.310   1.00   60.71   C       ATOM   2279   CD1   TYR   B   136   28.328   14.701   12.541   1.00   63.40   C       ATOM   2280   CE1   TYR   B   136   28.547   13.453   13.099   1.00   63.12   C       ATOM   2281   CZ   TYR   B   136   28.892   13.353   14.431   1.00   61.25   C       ATOM   2282   OH   TYR   B   136   29.120   12.116   14.984   1.00   61.58   O       ATOM   2283   CE2   TYR   B   136   29.008   14.494   15.216   1.00   64.20   C       ATOM   2284   CD2   TYR   B   136   28.772   15.743   14.654   1.00   59.76   C       ATOM   2285   C   TYR   B   136   26.636   18.985   11.820   1.00   52.48   C       ATOM   2286   O   TYR   B   136   26.701   19.225   10.613   1.00   52.71   O       ATOM   2287   N   ILE   B   137   26.509   19.926   12.750   1.00   51.25   N       ATOM   2288   CA   ILE   B   137   26.430   21.344   12.443   1.00   48.75   C       ATOM   2289   CB   ILE   B   137   24.975   21.849   12.481   1.00   51.09   C       ATOM   2290   CG1   ILE   B   137   24.223   21.481   11.180   1.00   50.13   C       ATOM   2291   CD1   ILE   B   137   22.704   21.633   11.274   1.00   47.53   C       ATOM   2292   CG2   ILE   B   137   24.941   23.358   12.811   1.00   40.73   C       ATOM   2293   C   ILE   B   137   27.240   22.060   13.510   1.00   48.65   C       ATOM   2294   O   ILE   B   137   26.978   21.897   14.709   1.00   46.02   O       ATOM   2295   N   ILE   B   138   28.208   22.864   13.067   1.00   46.40   N       ATOM   2296   CA   ILE   B   138   29.125   23.546   13.969   1.00   44.96   C       ATOM   2297   CB   ILE   B   138   30.534   22.873   13.957   1.00   46.61   C       ATOM   2298   CG1   ILE   B   138   31.170   22.955   12.558   1.00   44.58   C       ATOM   2299   CD1   ILE   B   138   32.693   22.657   12.515   1.00   36.53   C       ATOM   2300   CG2   ILE   B   138   30.468   21.423   14.466   1.00   48.73   C       ATOM   2301   C   ILE   B   138   29.285   24.999   13.548   1.00   46.45   C       ATOM   2302   O   ILE   B   138   28.681   25.433   12.583   1.00   45.73   O       ATOM   2303   N   SER   B   139   30.093   25.756   14.283   1.00   46.68   N       ATOM   2304   CA   SER   B   139   30.615   27.033   13.767   1.00   50.66   C       ATOM   2305   CB   SER   B   139   29.706   28.215   14.146   1.00   51.05   C       ATOM   2306   OG   SER   B   139   30.290   29.441   13.717   1.00   52.58   O       ATOM   2307   C   SER   B   139   32.023   27.264   14.314   1.00   50.78   C       ATOM   2308   O   SER   B   139   32.239   27.119   15.520   1.00   51.39   O       ATOM   2309   N   THR   B   140   32.964   27.625   13.438   1.00   50.11   N       ATOM   2310   CA   THR   B   140   34.352   27.920   13.864   1.00   54.13   C       ATOM   2311   CB   THR   B   140   35.409   27.282   12.924   1.00   52.12   C       ATOM   2312   OG1   THR   B   140   35.051   27.513   11.560   1.00   51.29   O       ATOM   2313   CG2   THR   B   140   35.493   25.775   13.164   1.00   56.06   C       ATOM   2314   C   THR   B   140   34.629   29.421   14.072   1.00   53.66   C       ATOM   2315   O   THR   B   140   35.762   29.833   14.319   1.00   54.84   O       ATOM   2316   N   SER   B   141   33.568   30.220   13.978   1.00   53.68   N       ATOM   2317   CA   SER   B   141   33.640   31.661   14.128   1.00   52.39   C       ATOM   2318   CB   SER   B   141   32.400   32.311   13.503   1.00   54.33   C       ATOM   2319   OG   SER   B   141   32.157   31.779   12.205   1.00   47.17   O       ATOM   2320   C   SER   B   141   33.722   31.968   15.609   1.00   54.75   C       ATOM   2321   O   SER   B   141   33.090   31.288   16.428   1.00   57.16   O       ATOM   2322   N   ASN   B   142   34.509   32.969   15.975   1.00   52.29   N       ATOM   2323   CA   ASN   B   142   34.741   33.204   17.392   1.00   51.16   C       ATOM   2324   CB   ASN   B   142   36.220   33.539   17.661   1.00   50.07   C       ATOM   2325   CG   ASN   B   142   36.473   34.996   17.869   1.00   55.16   C       ATOM   2326   OD1   ASN   B   142   36.678   35.743   16.915   1.00   61.85   O       ATOM   2327   ND2   ASN   B   142   36.509   35.414   19.136   1.00   51.49   N       ATOM   2328   C   ASN   B   142   33.736   34.157   18.063   1.00   51.20   C       ATOM   2329   O   ASN   B   142   33.895   34.521   19.238   1.00   51.08   O       ATOM   2330   N   GLY   B   143   32.719   34.570   17.299   1.00   50.47   N       ATOM   2331   CA   GLY   B   143   31.643   35.424   17.795   1.00   50.52   C       ATOM   2332   C   GLY   B   143   31.764   36.925   17.590   1.00   51.28   C       ATOM   2333   O   GLY   B   143   30.825   37.669   17.903   1.00   50.26   O       ATOM   2334   N   SER   B   144   32.898   37.376   17.056   1.00   53.07   N       ATOM   2335   CA   SER   B   144   33.265   38.799   17.086   1.00   55.66   C       ATOM   2336   CB   SER   B   144   34.725   38.939   17.504   1.00   55.64   C       ATOM   2337   OG   SER   B   144   35.557   38.164   16.662   1.00   55.12   O       ATOM   2338   C   SER   B   144   33.037   39.605   15.805   1.00   57.74   C       ATOM   2339   O   SER   B   144   32.699   40.803   15.873   1.00   58.24   O       ATOM   2340   N   LEU   B   145   33.237   38.964   14.651   1.00   58.51   N       ATOM   2341   CA   LEU   B   145   33.204   39.638   13.329   1.00   59.93   C       ATOM   2342   CB   LEU   B   145   32.877   41.138   13.436   1.00   59.99   C       ATOM   2343   CG   LEU   B   145   32.790   42.022   12.187   1.00   58.59   C       ATOM   2344   CD1   LEU   B   145   31.717   41.539   11.235   1.00   56.85   C       ATOM   2345   CD2   LEU   B   145   32.557   43.492   12.576   1.00   60.03   C       ATOM   2346   C   LEU   B   145   34.515   39.443   12.583   1.00   60.20   C       ATOM   2347   O   LEU   B   145   34.543   38.819   11.524   1.00   60.65   O       ATOM   2348   N   GLU   B   146   35.604   39.974   13.134   1.00   61.34   N       ATOM   2349   CA   GLU   B   146   36.928   39.772   12.538   1.00   62.60   C       ATOM   2350   CB   GLU   B   146   37.998   40.590   13.266   1.00   61.85   C       ATOM   2351   CG   GLU   B   146   38.123   42.030   12.766   1.00   64.43   C       ATOM   2352   CD   GLU   B   146   37.060   42.965   13.338   1.00   67.41   C       ATOM   2353   OE1   GLU   B   146   37.408   43.791   14.212   1.00   68.51   O       ATOM   2354   OE2   GLU   B   146   35.884   42.880   12.916   1.00   67.92   O       ATOM   2355   C   GLU   B   146   37.292   38.287   12.520   1.00   62.26   C       ATOM   2356   O   GLU   B   146   38.134   37.850   11.723   1.00   62.28   O       ATOM   2357   N   GLY   B   147   36.635   37.522   13.393   1.00   60.53   N       ATOM   2358   CA   GLY   B   147   36.785   36.077   13.424   1.00   58.38   C       ATOM   2359   C   GLY   B   147   35.703   35.336   12.662   1.00   57.21   C       ATOM   2360   O   GLY   B   147   35.808   34.128   12.464   1.00   56.76   O       ATOM   2361   N   LEU   B   148   34.675   36.069   12.229   1.00   57.52   N       ATOM   2362   CA   LEU   B   148   33.487   35.517   11.552   1.00   55.98   C       ATOM   2363   CB   LEU   B   148   32.674   36.661   10.914   1.00   56.73   C       ATOM   2364   OG   LEU   B   148   31.380   36.448   10.111   1.00   54.78   C       ATOM   2365   CD1   LEU   B   148   30.401   35.463   10.759   1.00   47.97   C       ATOM   2366   CD2   LEU   B   148   30.710   37.791   9.842   1.00   53.84   C       ATOM   2367   C   LEU   B   148   33.817   34.432   10.524   1.00   56.07   C       ATOM   2368   O   LEU   B   148   33.181   33.388   10.489   1.00   55.33   O       ATOM   2369   N   ASP   B   149   34.832   34.674   9.704   1.00   57.37   N       ATOM   2370   CA   ASP   B   149   35.228   33.712   8.675   1.00   57.71   C       ATOM   2371   CB   ASP   B   149   35.433   34.427   7.333   1.00   58.37   C       ATOM   2372   CG   ASP   B   149   35.787   35.901   7.504   1.00   59.20   C       ATOM   2373   OD1   ASP   B   149   36.457   36.258   8.508   1.00   58.54   O       ATOM   2374   OD2   ASP   B   149   35.383   36.700   6.635   1.00   60.63   O       ATOM   2375   C   ASP   B   149   36.466   32.893   9.080   1.00   58.10   C       ATOM   2376   O   ASP   B   149   37.213   32.410   8.220   1.00   57.61   O       ATOM   2377   N   ASN   B   150   36.680   32.742   10.390   1.00   56.91   N       ATOM   2378   CA   ASN   B   150   37.712   31.834   10.874   1.00   56.84   C       ATOM   2379   CB   ASN   B   150   37.912   31.931   12.396   1.00   55.39   C       ATOM   2380   CG   ASN   B   150   38.659   33.192   12.799   1.00   54.03   C       ATOM   2381   OD1   ASN   B   150   39.183   33.914   11.946   1.00   53.83   O       ATOM   2382   ND2   ASN   B   150   38.698   33.473   14.099   1.00   56.00   N       ATOM   2383   C   ASN   B   150   37.367   30.430   10.447   1.00   57.87   C       ATOM   2384   O   ASN   B   150   36.336   29.880   10.840   1.00   58.19   O       ATOM   2385   N   GLN   B   151   38.222   29.876   9.599   1.00   57.57   N       ATOM   2386   CA   GLN   B   151   38.005   28.551   9.045   1.00   58.65   C       ATOM   2387   CB   GLN   B   151   38.760   28.417   7.716   1.00   59.29   C       ATOM   2388   CG   GLN   B   151   38.337   29.449   6.648   1.00   55.33   C       ATOM   2389   CD   GLN   B   151   37.597   28.832   5.475   1.00   61.37   C       ATOM   2390   OE1   GLN   B   151   38.109   27.918   4.824   1.00   63.82   O       ATOM   2391   NE2   GLN   B   151   36.394   29.340   5.184   1.00   50.29   N       ATOM   2392   C   GLN   B   151   38.365   27.428   10.036   1.00   59.36   C       ATOM   2393   O   GLN   B   151   38.176   26.237   9.730   1.00   58.04   O       ATOM   2394   N   GLU   B   152   38.862   27.810   11.223   1.00   59.43   N       ATOM   2395   CA   GLU   B   152   39.181   26.833   12.272   1.00   60.25   C       ATOM   2396   CB   GLU   B   152   40.602   26.256   12.078   1.00   61.48   C       ATOM   2397   CG   GLU   B   152   41.747   27.124   12.625   1.00   66.64   C       ATOM   2398   CD   GLU   B   152   42.467   27.885   11.504   1.00   68.50   C       ATOM   2399   OE1   GLU   B   152   43.153   27.227   10.670   1.00   70.55   O       ATOM   2400   OE2   GLU   B   152   42.360   29.142   11.471   1.00   70.22   O       ATOM   2401   C   GLU   B   152   38.979   27.296   13.735   1.00   59.91   C       ATOM   2402   O   GLU   B   152   39.092   28.489   14.055   1.00   57.60   O       ATOM   2403   N   GLY   B   153   38.670   26.328   14.603   1.00   59.88   N       ATOM   2404   CA   GLY   B   153   38.611   26.530   16.052   1.00   61.08   C       ATOM   2405   C   GLY   B   153   37.320   27.083   16.638   1.00   62.49   C       ATOM   2406   O   GLY   B   153   36.298   26.389   16.676   1.00   61.87   O       ATOM   2407   N   GLY   B   154   37.397   28.340   17.090   1.00   63.05   N       ATOM   2408   CA   GLY   B   154   36.402   29.036   17.933   1.00   62.98   C       ATOM   2409   C   GLY   B   154   34.981   28.521   18.070   1.00   62.97   C       ATOM   2410   O   GLY   B   154   34.373   28.096   17.087   1.00   64.66   O       ATOM   2411   N   VAL   B   155   34.452   28.571   19.295   1.00   61.10   N       ATOM   2412   CA   VAL   B   155   33.051   28.238   19.574   1.00   57.44   C       ATOM   2413   CB   VAL   B   155   32.086   29.191   18.770   1.00   59.75   C       ATOM   2414   CG1   VAL   B   155   30.869   28.479   18.148   1.00   53.52   C       ATOM   2415   CG2   VAL   B   155   31.694   30.398   19.640   1.00   59.92   C       ATOM   2416   C   VAL   B   155   32.774   26.725   19.473   1.00   56.32   C       ATOM   2417   O   VAL   B   155   32.358   26.102   20.454   1.00   55.79   O       ATOM   2418   N   CYS   B   156   33.067   26.126   18.319   1.00   54.93   N       ATOM   2419   CA   CYS   B   156   33.049   24.667   18.173   1.00   54.61   C       ATOM   2420   CB   CYS   B   156   33.494   24.270   16.754   1.00   52.18   C       ATOM   2421   SG   CYS   B   156   33.580   22.483   16.410   1.00   54.42   S       ATOM   2422   C   CYS   B   156   33.909   23.990   19.278   1.00   54.64   C       ATOM   2423   O   CYS   B   156   33.407   23.164   20.052   1.00   54.63   O       ATOM   2424   N   GLN   B   157   35.187   24.360   19.371   1.00   55.54   N       ATOM   2425   CA   GLN   B   157   36.065   23.825   20.426   1.00   56.56   C       ATOM   2426   CB   GLN   B   157   37.535   23.863   19.983   1.00   56.95   C       ATOM   2427   C   GLN   B   157   35.892   24.528   21.791   1.00   56.30   C       ATOM   2428   O   GLN   B   157   35.845   23.877   22.843   1.00   57.99   O       ATOM   2429   N   THR   B   158   35.780   25.856   21.755   1.00   54.56   N       ATOM   2430   CA   THR   B   158   35.832   26.703   22.947   1.00   51.87   C       ATOM   2431   CB   THR   B   158   36.082   28.197   22.528   1.00   53.75   C       ATOM   2432   OG1   THR   B   158   37.496   28.431   22.411   1.00   49.36   O       ATOM   2433   CG2   THR   B   158   35.470   29.201   23.512   1.00   52.72   C       ATOM   2434   C   THR   B   158   34.632   26.566   23.900   1.00   51.82   C       ATOM   2435   O   THR   B   158   34.800   26.579   25.128   1.00   52.22   O       ATOM   2436   N   ARG   B   159   33.441   26.403   23.335   1.00   49.63   N       ATOM   2437   CA   ARG   B   159   32.187   26.495   24.078   1.00   49.75   C       ATOM   2438   CB   ARG   B   159   31.544   27.873   23.850   1.00   47.71   C       ATOM   2439   C   ARG   B   159   31.223   25.388   23.657   1.00   50.64   C       ATOM   2440   O   ARG   B   159   30.016   25.478   23.906   1.00   52.26   O       ATOM   2441   N   ALA   B   160   31.780   24.338   23.045   1.00   49.93   N       ATOM   2442   CA   ALA   B   160   31.031   23.199   22.492   1.00   48.16   C       ATOM   2443   CB   ALA   B   160   30.681   22.213   23.589   1.00   47.09   C       ATOM   2444   C   ALA   B   160   29.781   23.593   21.693   1.00   47.13   C       ATOM   2445   O   ALA   B   160   28.729   22.967   21.837   1.00   46.20   O       ATOM   2446   N   MET   B   161   29.897   24.650   20.888   1.00   48.64   N       ATOM   2447   CA   MET   B   161   28.791   25.123   20.060   1.00   50.67   C       ATOM   2448   CB   MET   B   161   28.928   26.603   19.706   1.00   52.39   C       ATOM   2449   CG   MET   B   161   28.155   27.506   20.613   1.00   51.45   C       ATOM   2450   SD   MET   B   161   27.427   28.867   19.687   1.00   55.07   S       ATOM   2451   CE   MET   B   161   26.010   29.168   20.740   1.00   54.49   C       ATOM   2452   C   MET   B   161   28.658   24.300   18.803   1.00   49.34   C       ATOM   2453   O   MET   B   161   29.151   24.659   17.730   1.00   48.03   O       ATOM   2454   N   LYS   B   162   27.994   23.170   18.953   1.00   49.25   N       ATOM   2455   CA   LYS   B   162   27.692   22.303   17.820   1.00   48.55   C       ATOM   2456   CB   LYS   B   162   28.860   21.354   17.556   1.00   51.62   C       ATOM   2457   CG   LYS   B   162   29.575   20.893   18.800   1.00   49.28   C       ATOM   2458   CD   LYS   B   162   31.087   20.929   18.634   1.00   50.58   C       ATOM   2459   CE   LYS   B   162   31.753   20.166   19.772   1.00   50.05   C       ATOM   2460   NZ   LYS   B   162   33.254   20.284   19.818   1.00   49.37   N       ATOM   2461   C   LYS   B   162   26.373   21.547   18.060   1.00   49.72   C       ATOM   2462   O   LYS   B   162   25.916   21.410   19.222   1.00   43.36   O       ATOM   2463   N   ILE   B   163   25.736   21.121   16.963   1.00   47.99   N       ATOM   2464   CA   ILE   B   163   24.568   20.251   17.040   1.00   47.17   C       ATOM   2465   CB   ILE   B   163   23.306   20.835   16.329   1.00   46.99   C       ATOM   2466   CG1   ILE   B   163   22.952   22.213   16.880   1.00   46.43   C       ATOM   2467   CD1   ILE   B   163   21.965   22.944   16.019   1.00   56.53   C       ATOM   2468   CG2   ILE   B   163   22.082   19.898   16.490   1.00   43.12   C       ATOM   2469   C   ILE   B   163   24.929   18.931   16.392   1.00   47.16   C       ATOM   2470   O   ILE   B   163   25.505   18.905   15.299   1.00   47.77   O       ATOM   2471   N   LEU   B   164   24.586   17.844   17.085   1.00   47.94   N       ATOM   2472   CA   LEU   B   164   24.639   16.492   16.538   1.00   47.40   C       ATOM   2473   CB   LEU   B   164   25.458   15.602   17.485   1.00   48.90   C       ATOM   2474   CG   LEU   B   164   25.515   14.084   17.312   1.00   48.11   C       ATOM   2475   CD1   LEU   B   164   25.891   13.674   15.901   1.00   52.59   C       ATOM   2476   CD2   LEU   B   164   26.497   13.532   18.324   1.00   46.10   C       ATOM   2477   C   LEU   B   164   23.210   15.947   16.335   1.00   48.56   C       ATOM   2478   O   LEU   B   164   22.455   15.805   17.301   1.00   47.48   O       ATOM   2479   N   MET   B   165   22.836   15.666   15.078   1.00   49.17   N       ATOM   2480   CA   MET   B   165   21.500   15.120   14.757   1.00   48.85   C       ATOM   2481   CB   MET   B   165   20.840   15.899   13.620   1.00   48.68   C       ATOM   2482   CG   MET   B   165   20.442   17.324   14.038   1.00   51.96   C       ATOM   2483   SD   MET   B   165   20.732   18.576   12.780   1.00   52.67   S       ATOM   2484   CE   MET   B   165   22.520   18.375   12.593   1.00   54.06   C       ATOM   2485   C   MET   B   165   21.509   13.624   14.460   1.00   47.92   C       ATOM   2486   O   MET   B   165   22.112   13.162   13.481   1.00   43.94   O       ATOM   2487   N   LYS   B   166   20.820   12.893   15.332   1.00   49.57   N       ATOM   2488   CA   LYS   B   166   20.791   11.437   15.337   1.00   50.86   C       ATOM   2489   CB   LYS   B   166   21.118   10.881   16.748   1.00   50.14   C       ATOM   2490   CG   LYS   B   166   22.499   11.269   17.311   1.00   44.29   C       ATOM   2491   CD   LYS   B   166   22.993   10.265   18.367   1.00   51.13   C       ATOM   2492   CE   LYS   B   166   24.398   9.728   18.020   1.00   44.96   C       ATOM   2493   NZ   LYS   B   166   25.262   9.450   19.224   1.00   51.45   N       ATOM   2494   C   LYS   B   166   19.437   10.891   14.869   1.00   52.27   C       ATOM   2495   O   LYS   B   166   18.388   11.185   15.452   1.00   49.95   O       ATOM   2496   N   VAL   B   167   19.466   10.116   13.793   1.00   53.68   N       ATOM   2497   CA   VAL   B   167   18.484   9.043   13.659   1.00   55.69   C       ATOM   2498   CB   VAL   B   167   17.754   8.987   12.300   1.00   53.78   C       ATOM   2499   CG1   VAL   B   167   16.393   8.309   12.485   1.00   51.87   C       ATOM   2500   CG2   VAL   B   167   17.564   10.378   11.706   1.00   60.81   C       ATOM   2501   C   VAL   B   167   19.221   7.728   13.947   1.00   56.53   C       ATOM   2502   O   VAL   B   167   20.288   7.731   14.582   1.00   55.95   O       ATOM   2503   O   HOH   C   1   −1.068   19.700   −2.247   1.00   20.00   O       ATOM   2504   O   HOH   D   2   15.644   38.458   −11.327   1.00   20.00   O       ATOM   2505   O   HOH   D   3   −8.095   49.449   −9.306   1.00   20.00   O       ATOM   2506   O   HOH   D   4   14.879   14.522   19.283   1.00   20.00   O       ATOM   2507   O   HOH   D   5   19.086   43.782   7.312   1.00   20.00   O       ATOM   2508   O   HOH   D   6   3.762   36.483   −0.689   1.00   20.00   O       ATOM   2509   O   HOH   D   7   5.977   28.240   −23.712   1.00   20.00   O       ATOM   2510   O   HOH   D   9   38.280   30.933   15.129   1.00   20.00   O       ATOM   2511   O   HOH   D   10   −2.614   8.973   −12.882   1.00   20.00   O       ATOM   2512   O   HOH   D   11   33.557   12.755   6.451   1.00   20.00   O       ATOM   2513   O   HOH   D   12   13.880   42.897   11.851   1.00   20.00   O       ATOM   2514   O   HOH   D   13   19.942   29.901   −7.927   1.00   20.00   O       ATOM   2515   O   HOH   D   14   20.613   48.185   26.172   1.00   20.00   O       ATOM   2516   O   HOH   D   15   23.384   36.996   17.915   1.00   20.00   O       ATOM   2517   O   HOH   D   16   12.029   8.173   11.014   1.00   20.00   O       ATOM   2518   O   HOH   D   18   17.554   21.123   −23.737   1.00   20.00   O       ATOM   2519   O   HOH   D   19   34.755   13.969   18.956   1.00   20.00   O       ATOM   2520   O   HOH   D   20   19.454   17.871   −19.578   1.00   20.00   O       ATOM   2521   O   HOH   D   21   16.241   30.564   5.560   1.00   20.00   O       ATOM   2522   O   HOH   D   22   4.906   11.442   0.110   1.00   20.00   O       ATOM   2523   O   HOH   D   23   0.407   21.483   −3.061   1.00   20.00   O       ATOM   2524   O   HOH   D   24   11.613   15.180   −2.107   1.00   20.00   O       ATOM   2525   O   HOH   D   25   3.322   26.535   2.926   1.00   20.00   O       ATOM   2526   O   HOH   D   26   0.515   33.846   2.133   1.00   20.00   O       ATOM   2527   O   HOH   D   27   20.755   10.411   1.428   1.00   20.00   O       ATOM   2528   O   HOH   D   28   17.637   11.370   −10.183   1.00   20.00   O       ATOM   2529   O   HOH   D   29   25.321   5.436   7.341   1.00   20.00   O       ATOM   2530   O   HOH   D   30   12.205   9.020   −7.002   1.00   20.00   O       ATOM   2531   O   HOH   D   31   10.319   15.291   −12.878   1.00   20.00   O       ATOM   2532   O   HOH   D   32   13.474   26.530   21.387   1.00   20.00   O       ATOM   2533   O   HOH   D   33   −5.385   36.132   3.825   1.00   20.00   O       ATOM   2534   O   HOH   D   34   −12.238   40.692   −6.393   1.00   20.00   O       ATOM   2535   O   HOH   D   35   −7.910   35.441   3.507   1.00   20.00   O       ATOM   2536   O   HOH   D   36   16.595   21.733   4.395   1.00   20.00   O       ATOM   2537   O   HOH   D   37   6.286   16.055   −2.458   1.00   20.00   O       ATOM   2538   O   HOH   D   38   5.079   15.735   −7.772   1.00   20.00   O       ATOM   2539   O   HOH   D   39   0.584   7.759   −10.414   1.00   20.00   O       ATOM   2540   O   HOH   D   40   11.416   24.606   13.912   1.00   20.00   O       ATOM   2541   O   HOH   D   43   9.303   12.604   −3.017   1.00   20.00   O       ATOM   2542   O   HOH   D   45   28.991   19.384   1.268   1.00   20.00   O       ATOM   2543   O   HOH   D   46   21.356   43.725   10.404   1.00   20.00   O       ATOM   2544   O   HOH   D   49   −12.300   34.162   −0.864   1.00   20.00   O       END                  
 
         [0076]    
       
         
               
             
               
               
               
             
           
               
                 TABLE 2 
               
               
                   
               
               
                   
               
               
                 Crystallographic Statistics for the EphB4-ephrinB2 Complex 
               
               
                   
               
             
             
               
                   
               
             
          
           
               
                   
                 Resolution (Å) 1   
                 20-2.0 (2.1-2.0) 
               
               
                   
                 Wavelength (Å) 
                 0.98 
               
               
                   
                 Space Group 
                 P4 1   
               
               
                   
                 Unit Cell Dimensions (Å) 
                 a = b = 81.09 81.09 c = 50.95 
               
               
                   
                 Completeness (%) 
                 99.6 (99.9) 
               
               
                   
                 R sym  (%) 2   
                  3.9 (20.8) 
               
               
                   
                 l/σ 
                 4.8 
               
               
                   
                 Mean Redundancy 
                 4.7 
               
               
                   
                 No. Reflections 
                 19,785 
               
               
                   
                 R cryst  (%) 3   
                 22.6 (26.5) 
               
               
                   
                 R free  (%) 4   
                 29.5 (30.0) 
               
               
                   
                 R.m.s. deviations 
               
               
                   
                 Bond length (Å) 
                 0.02 
               
               
                   
                 Bond angle (°) 
                 1.7 
               
               
                   
                 Average B factor (Å 2 ) 
                 56.6 
               
               
                   
                 Number of atoms 
               
               
                   
                 Protein 
                 4,992 
               
               
                   
                   
               
               
                   
                     1 Number in parentheses is for the highest shell.    
               
               
                   
                     2 R sym  = Σ|I − &lt;I&gt;|/ΣI, where I is the observed intensity and &lt;I&gt; is the average intensity of multiple symmetry-related observations of that reflection.    
               
               
                   
                     3 R cryst  = Σ||F obs | − |F calc ||/Σ|F obs |, where F obs  and F calc  are the observed and calculated structure factors. R sym  = Σ|I − &lt;I&gt;|/ΣI, where I is the observed intensity and &lt;I&gt; is the average intensity of multiple symmetry-related observations of that reflection.    
               
               
                   
                     4 R free  = Σ||F obs | − |F calc ||/Σ|F obs | for 10% of the data not used at any stage of structural refinement.    
               
             
          
         
       
     
         [0077]    
       
         
               
             
               
               
               
             
           
               
                 TABLE 3 
               
             
             
               
                   
               
               
                   
               
               
                 Effects of EphB4 mutation on binding to Alexa-532-TNYL-RAW 
               
             
          
           
               
                   
                 EphB4 mutant 
                 Kd, nM 
               
               
                   
                   
               
               
                   
                 WT 
                   5 ± 0.9 
               
               
                   
                 L95R 
                 ND* 
               
               
                   
                 T147F 
                  25 ± 5.6 
               
               
                   
                 R148S 
                 4.5 ± 0.7 
               
               
                   
                 K149Q 
                 23 ± 8  
               
               
                   
                 R150V 
                 6.1 ± 0.8 
               
               
                   
                 RKR148-150SQV 
                 21 ± 6  
               
               
                   
                 A186S 
                 16 ± 4  
               
               
                   
                   
               
               
                   
                   *FP window is not significant to accurately determine Kd    
               
             
          
         
       
     
         [0078]    
       
         
               
             
               
               
               
               
               
               
             
           
               
                 TABLE 4 
               
             
             
               
                   
               
               
                   
               
               
                 Binding of peptide (TNYL-RAW) and human ephrinB2 to the human EphB4 
               
               
                 ephrin-binding domain and EphB4 mutants. Experiments were performed at 
               
               
                 25° C. in 50 mM Tris pH 7.8, 150 mM NaCl, 1 mM CaCl 2 . 
               
               
                 All values represent the average of at least two experiments. 
               
             
          
           
               
                   
                   
                 Kd 
                 ΔG 
                 ΔH 
                 TΔS 
               
               
                 Receptor 
                 Ligand 
                 (nM) 
                 (kcal mol−1) 
                 (kcal mol−1) 
                 (kcal mol−1) 
               
               
                   
               
               
                 EphB4 (wt) 
                 ephrinB2 
                 40 ± 20 
                 −10.2 ± 0.3   
                  3.3 ± 0.1 
                 13.4 ± 0.4 
               
               
                 EphB4 
                 ephrinB2 
                 20 ± 10 
                 −10.6 ± 0.4   
                  3.7 ± 0.2 
                 14.4 ± 0.3 
               
               
                 (K149Q) 
               
               
                 EphB4 
                 ephrinB2 
                 1900 ± 1100 
                 −7.8 ± 0.3 
                  5.2 ± 0.7 
                 13.0 ± 0.8 
               
               
                 (L95R) 
               
               
                 EphB4 (wt) 
                 TNYL-RAW 
                 71 ± 14 
                 −9.8 ± 0.1 
                 −14.7 ± 0.2 
                 −4.9 ± 0.2 
               
               
                 EphB4 
                 TNYL-RAW 
                 160 ± 120 
                 −9.4 ± 0.5 
                 −12.5 ± 1.2 
                 −3.2 ± 1.3 
               
               
                 (K149Q) 
               
               
                 EphB4 
                 TNYL-RAW 
                 35900 ± 5000  
                 −6.1 ± 0.1 
                 −12.0 ± 0.3 
                 −5.8 ± 0.4 
               
               
                 (L95R) 
               
               
                   
               
             
          
         
       
     
       EXAMPLES  
       [0079]     Aspects of the present teachings may be further understood in light of the following examples, which should not be construed as limiting the scope of the present teachings in any way.  
       Example 1  
     Construct Design, Expression and Purification of EphB4  
       [0080]     Twelve sequential 4 amino acid truncations in human EphB4 were designed based on EphB4-EphB2 sequence alignment in the region C-terminal to the last β-strand in the EphB2 structure. The resulting fragments were cloned into the insect cell expression vector pBAC6 (Novagen, Wis.) under control of the heterologous GP64 signal peptide and containing a N-terminal six histidine tag. Constructs were sequence verified, and baculovirus was generated using homologous recombination into Sapphire Baculovirus DNA (Orbigen, Calif.) using the manufacturers protocol. After 3 rounds of viral amplification, a small scale expression screen was conducted for all constructs in both Sf9 and Hi5 insect cells. Briefly, 5×10 6  cells were infected with baculovirus at an MOI of 2 in 38 mm tissue culture dishes; cells were harvested at 48 hours post infection and supernatant containing secreted EphB4 was concentrated 10-fold and buffer exchanged into 50 mM Tris pH 7.8, 400 mM NaCl, and 5 mM imidazole using an Amicon Ultra 5K concentrator (Millipore, MS). The secreted protein was bound to Ni-NTA magnetic beads (Qiagen, CA), washed with 50 mM Tris pH 7.8, 400 mM NaCl, 20 mM Imidazole buffer and eluted with 50 mM Tris pH 7.8, 400 mM NaCl, 250 mM Imidazole. Based on analysis of immobilized metal affinity chromatography (IMAC) elutes, the EphB4 (17-196) construct was identified as the highest expressor at ˜6 mg/L in Hi5 insect cells. Large scale expression was conducted using Wave Bioreactors (Wave Biotech LLC, NJ) at a MOI of 2 for 48 hours in Hi5 insect cells. Media containing secreted EphB4 was concentrated and buffer exchanged using a Hydrosart Crossflow filter (Sartorius, NY). Following IMAC purification on ProBond resin (Invitrogen, CA) as described above, EphB4 was concentrated to 5 mg/ml and loaded on a Superdex 75 16/60 column (GE HealthCare, N.Y.). A small amount of aggregated material was removed by preparative size exclusion chromatography, while most of the sample eluted in a single peak corresponding to an EphB4 (17-196) monomer. The complete removal of the GP64 secretion sequence and protein identity were confirmed by MALDI analysis.  
         [0081]     The wtEphB4 construct was used as a template for the generation of site specific mutants. The human ephrinB2 (extracellular domain; residues 25-187) was designed based on the previously published EphB2-ephrinB2 structure and cloned into a modified pFastBac1 vector containing a GP67 leader peptide. Recombinant baculovirus was generated using the Bac-to-Bac system (Invitrogen, CA). Briefly, large scale expression of ephrinB2 was carried out using Wave Bioreactors on a 5 L scale at an MOI of 5 for 48 hr. resulting in 10 mg of ephrinB2 per liter of Hi-5 insect cells (Invitrogen, CA). Media containing secreted ephrinB2 protein was concentrated and buffer exchanged using a Hydrostart Crossflow Filter (Sartorius Edgewood, N.Y.). The ligand was purified by immobilized metal affinity chromatography (IMAC), and cleaved overnight with TEV protease. Material was further re-purified by IMAC chromatography to remove the protease and an N-terminal fragment containing the histidine tag. The EphB4-ephrinB2 complex was formed with a 1.5-fold molar excess of ephrinB2 overnight at 4° C. in buffer containing 50 mM Tris, pH 7.8, 100 mM NaCl, and 10 mM Imidazole. The complex was purified by IMAC chromatography, followed by size exclusion chromatography to remove trace aggregates (Phenomenex S2000).  
       Example 2  
     Crystallization, Data Collection, and Structure Solution  
       [0082]     The EphB4-ephrinB2 complex was concentrated to 20 mg/mL and crystallized by sitting drop vapor diffusion at 20° C. against a precipitant of 2.2 M ammonium sulfate and 100 mM tris, pH 7.8. Crystals formed in the P4 1  spacegroup and contained one monomer of receptor and one monomer of ligand in the asymmetric unit. Data were collected at the Advance Photon Source (Argonne, IL) on beamline GM/CA-CAT. Images were processed and reduced using HKL2000 (31). The structure was solved by molecular replacement with MolRep (CCP4i), using the EphB2-ephrinB2 structure (PDB: 1 KGY) as a search model (10,32). The structure was refined by a rigid body refinement, followed by model building in 0 and iterative refinements with refmac (32,33). The structure exhibits good geometry with no Ramachandran outliers.  
       Example 3  
     Isothermal Titration Calorimetry  
       [0083]     All mutants and ligands were dialyzed into buffer containing 50 mM Tris-Cl (pH 7.8), 150 mM NaCl, and 1 mM CaCl 2  prior to use in isothermal titration calorimetry (ITC) experiments. All experiments were performed with a Microcal MCS ITC at 25° C. Titrations were completed as described in Example 4. EphB4 (wild-type or mutant) was present in the sample cell at a concentration of 12 to 15 μM and the injection syringe contained either 127 μM ephrinB2 or 200 μM TNYL-RAW. Titrations of TNYL-RAW with the L95R mutant of EphB4 were performed with 2 mM TNYL-RAW in the injection syringe and 15 μM EphB4 (L95R) in the sample cell. Data for these titrations were fit assuming a stoichiometry of 1 and at least 60% saturation at the final peptide concentration as described (19,34).  
       Example 4  
       [0084]     Isothermal titration calorimetry and ELISA experiments: EphB4 and ephrin-B2 were either dialyzed or buffer exchanged into 50 mM Tris-Cl (pH 7.8 at 25° C.), 150 mM NaCl, 1 mM CaCl 2 , prior to use in calorimetry experiments. Peptides were dissolved into the same buffer used for the dialysis of EphB4. The concentration of EphB4, ephrin-B2 and the peptides was determined by measuring the A 280  and using the theoretical extinction coefficient (Gill and von Hippel, 1989). ITC experiments were performed with a Microcal MCS ITC at 25° C. Following an initial injection of 2 μl, titrations were performed by making 20 13 μl injections of peptide into EphB4 in the sample cell to produce an approximate final 2:1 ratio of injectant to sample in the cell. For most titrations the sample cell contained 15 μM EphB4 and the injection syringe contained a 200 μM solution of the peptide. Titrations with ephrin-B2 contained 13 μM EphB4 in the sample cell and 290 μM ephrin-B2 in the syringe. Prior to loading the sample cell, EphB4 was centrifuged at 18,000 g for 5 min at 4° C. to remove aggregates and degassed for 5 minutes at room temperature. Corrections for heats of dilution for the peptides and ephrin-B2 were determined by performing titrations of peptide or ephrin-B2 solutions into buffer. Dilution data were fit to a line and subtracted from the corresponding titration data. Titration data were analyzed using Origin ITC software (Version 5.0, Microcal Software Inc.) and curves were fit to a single binding site model (Wiseman et al., 1989). The low affinity of the TNYL peptide and the limited availability of EphB4 (17-196) precluded accurate determination of the K d  for this interaction by ITC. A lower limit for the binding constant was determined by performing a titration in which the sample cell contained 30 μM EphB4 and the injection syringe contained a 1.45 mM solution of the peptide, producing a final ratio of peptide to EphB4 of 10:1. The data was fit assuming a stoichiometry of 1 and at least 60% saturation of binding at the final peptide concentration (Turnbull and Daranas, 2003).  
         [0085]     The ability of peptides to compete the binding of mouse ephrin-B2 alkaline phosphatase to immobilized mouse EphB4-Fc-His (R&amp;D Systems) was measured by ELISA as previously described (Koolpe et al., 2005).  
       Example 5  
       [0086]     This Example illustrates fluorescence polarization (FP) assays using a fluorescently-labeled reporter peptide to measure binding of various ligands to the EphB4-LBD.  
         [0087]     We have evaluated TMR and Alexa-532 labeled peptides, and experimentally confirmed the preference of Alexa-532-TNYL-RAW peptide for the assay because of the better dynamic range. We have also evaluated mutants predicted to have altered binding affinity to the TNYL-RAW peptide based on structural observations. The dose-response curve in  FIG. 6A  shows the wild-type EphB4 and EphB4 K149Q mutant signal upon binding to labeled TNYL-RAW peptide. AK149Q mutant has a greater dynamic range and slightly lower affinity for the labeled peptide than wtEphB4. In competition experiments, the affinity for the TNYL-RAW peptide is 170 nM, which is slightly lower than for wtEphB4 (100 nM) ( FIG. 7 ). Without being bound by a particular theory, a better dynamic range is likely a result of the interaction of this specific mutant with the Alexa-532 fluorophore of the reporter peptide. These characteristics make it an attractive tool for high throughput screening. The assay windows are approximately 6-fold for wtEphB4 and 12-fold for the EphB4 (K149Q) mutant. In addition we have validated the assay by studying binding of an L95R mutant, which was shown to have Kdephrin-B2=2 uM by ITC analysis. We have not detected a significant signal in FP analysis to accurately calculate KdAlexa-TNYL-RAW ( FIG. 6B ). This analysis also further validates the use of labeled TNYL-RAW peptide as a surrogate ligand for studies of ephrin-B2-EphB4 binding.  
         [0088]     In this and other examples involving Alexa-532-TNYL-RAW peptide, A serial dilution of EphB4 was prepared in Assay Buffer (50 mM Tris pH 7.8, 150 mM NaCl, 1 mM CalCl2, 0.1% Pluronic 124). TNYL-RAW-Alexa-532 labeled peptide was prepared as a 100 μM stock solution in the Assay Buffer and a 300 nM working solution was made fresh prior to the measurements by dilution in the assay buffer. 5 μL of serially diluted EphB4 (9 nM-2362 nM concentration range) was combined with 5 μL of labeled peptide (final concentration 75 nM) in the final volume of 20 μL (Assay plate, 384 well flat bottom, black polystyrene, non-binding surface, Corning, cat #3654) in the absence and presence of 200 μM TNYL-RAW as a control for non-specific binding. The mixture was allowed to equilibrate for 30 min at room temperature, and measurements were performed with a Tecan Genios Pro (Tecan Instruments) using 535 nm excitation and 580 nm emission wavelength. All experimental data were analyzed using Prism 4.0 software (GraphPad Software Inc., San Diego, Calif.) and Kd values were generated by fitting the experimental data using a one-site binding hyperbola nonlinear regression model or equation 8.10 (.www.invitrogen.com/downloads/FP8.pdf).  
         [0089]     In these experiments, the human EphB4 (17-196) ligand binding domain was cloned into the insect cell expression vector pBAC6 (Novagen, San Diego, Calif.) under control of the heterologous GP64 signal peptide and containing an N-terminal six histidine tag. The construct was sequence verified, and baculovirus was generated with homologous recombination into Sapphire Baculovirus DNA (Orbigen, San Diego, Calif.) following the manufacturer&#39;s protocol (10). The wtEphB4 construct was used as a template for generation of site specific mutants.  
         [0090]     Large-scale expression was conducted with Wave Bioreactors (Wave Biotech LLC, Somerset, N.J.) at an MOI of 2 for 48 hr in Hi5 insect cells. Media containing secreted EphB4 (17-196) was concentrated and buffer exchanged with a Hydrosart Crossflow filter (Sartorius, Edgewood, N.Y.). Following immobilized metal affinity chromatography (IMAC) purification on ProBond resin (Invitrogen, Carlsbad, Calif.), EphB4 was concentrated to 5 mg/ml and loaded on a Superdex 75 16/60 column (GE HealthCare, Chicago, Ill.). A small amount of aggregated material was removed by preparative size exclusion chromatography, while most of the sample eluted in a single peak corresponding to an EphB4 (17-196) monomer. The complete removal of the GP64 secretion sequence and protein identity were confirmed by MALDI analysis.  
         [0091]     The TNYL-RAW peptide was labeled with Alexa-532 (Biopeptides Inc., San Diego, Calif.). All peptides are purified to &gt;95% purity, and supplied with rigorous analytical specifications, including HPLC and MS analysis.  
       Example 6  
       [0092]     This Example illustrates that the fluorescence polarization assay (Example 5) is tolerant of organic solvents.  
         [0093]     In these experiments, dimethylsulfoxide (DMSO) was added in various concentrations to a solution comprising Eph4 and Alexa-532-TNYL-RAW peptide, and FP was measured. As shown in  FIG. 8 , the FP assay is tolerant to 5% DMSO (filled diamonds in  FIG. 8 ) as indicated by analysis of EphB4 binding in the presence of various concentrations of DMSO. We have also been successful in the crystallization of EphB4 with the TNYL-RAW peptide in the presence of 5% DMSO, which is indicative of excellent tolerance of this specific interaction to DMSO.  
       Example 7  
       [0094]     This Example illustrates determination of Z-factor at protein concentrations representing upper and lower plateaus of the dose response curve for the EphB4 K149Q mutant ( FIG. 6A ). The calculated Z-factor for 108 samples, each at 2 different protein concentrations, is 0.715 ( FIG. 9 ). The range of Z-factor between 0.5 and 1 is considered to be representative of a high quality assay.  
       Example 8  
       [0095]     This Example illustrates thermodynamic characterization of TNYL-RAW peptide binding to EphB4-ligand binding domain (EphB4-LBD).  
         [0096]     In these experiments, we monitored the binding of EphB4-LBD to ephrin-B2 and peptide ligands using isothermal titration calorimetry (ITC). The interaction between EphB4 (17-196) and ephrin-B2 yielded a Kd of 40 nM and a ΔHo of +3.3 kcal mol-1. This is slightly lower than the affinity reported for the interaction between the entire mouse EphB4 extracellular domain and mouse or human ephrin-B2. Without being limited by theory, we hypothesize that the difference may be explained by the existence of a third low affinity Eph-ephrin interface located outside the ephrin-binding domain (Smith, F. M., et al., J. Biol. Chem. 279: 9522-9531, 2004. In addition, N- and C-terminal truncations of the peptide, as well as targeted mutations in the center of the peptide, were synthesized in order to biophysically validate individual effects of the peptide upon EphB4 binding. Table 5 presents data of a thermodynamic analysis of wtEphB4 and mutant EphB4 binding to ephrin-B2 and TNYL-RAW and related peptides. The table shows the results of isothermal titration calorimetry (ITC) analysis. The Kd values reported from this method compare well with the Kd values determined from the FP assays ( FIGS. 6 and 7 ). Three regions of interactions proved critical for receptor binding: The N-terminal Tyr, the Phe/IIe amino acids in the center of the peptide, and the high-affinity C-terminal RAW sequence. The N- and C-terminal truncations appear detrimental due to the loss of stability at the D-E (N-terminal) and J-K (C-terminal) loops, while the Phe/IIe mutations resulted in a loss of stability at an imperative disulfide bridge critical to EphB4 LBD stability.  
                                   TABLE 5                                   ΔG (kcal       TΔS (kcal       Receptor   Ligand   Kd (nM)   mol−1)   ΔH (koal mol−1)   mol−1)                   EphB4 (wt)   ephrin-B2   40 ± 20   −10.2 ± 0.3     3.3 ± 0.1   13.4 ± 0.4       EphB4   ephrin-B2   20 ± 10   −10.5 ± 0.4     3.6 ± 0.1   14.1 ± 0.4       (K149Q)       EphB4   ephrin-B2   1900 ± 1100   −7.8 ± 0.3    5.2 ± 0.7   13.0 ± 0.8       (L95R)       EphB4 (wt)   TNYL-RAW   71 ± 14   −9.8 ± 0.1   −14.7 ± 0.2    −4.9 ± 0.2       EphB4   TNYL-RAW   250 ± 50    −9.0 ± 0.1   −11.7 ± 0.2    −2.7 ± 0.2       (K149Q)       EphB4 (wt)   NYLF-RAW   65 ± 7    −9.8 ± 0.1   −15.5 ± 0.1    −5.7 ± 0.1       EphB4 (wt)   YLFS-RAW   80 ± 36   −9.7 ± 0.2   −13.8 ± 0.5    −4.1 ± 0.4       EphB4 (wt)   LFSP-RAW   3,500 ± 680     −7.4 ± 0.1   −5.3 ± 0.5     2.1 ± 0.4       EphB4 (wt)   TNYL   ≧140,000   ND   −9.6 ± 0.3   ND       EphB4 (wt)   LFSP-RAW(F to   ≧500,000   ND   −7.9 ± 0.9   ND           A)       EphB4 (wt)   LFSP-RAW(I to   60,000 ± 20,000   −5.7 ± 0.1   −2.7 ± 0.3    3.0 ± 0.4,           A)                  
 
         [0097]     Results  
         [0098]     Anti-EphB4-ephrinB2 therapeutic development can be accomplished by providing the three dimensional crystal structure of the EphB4-ephrinB2 complex at a high resolution. EphB4 specificity can also be probed using the three dimensional crystal structure. In addition, site-directed mutagenesis and biophysical analyses were conducted to investigate the role of several residues within the ligand binding cavity of EphB4 in contributing to the binding of both ephrinB2 and the antagonistic TNYL-RAW peptide. These results allow the development of predictive models for structure-based drug design of small molecule compounds for use as therapeutics and to probe the biology of EphB4-ephrinB2 bi-directional signaling.  
         [0099]     Overall Structure  
         [0100]     EphB4 and ephrinB2 were co-concentrated to 20 mg/mL and crystallized by sitting drop vapor diffusion against a precipitant of 2.2 M ammonium sulfate and 100 mM Tris, pH 7.8 at 20° C. The co-crystal structure was refined to 2.0 Å resolution with an R-factor of 22.6% and a free R factor of 29.5% (Table 1). Unlike crystals of the of the EphB2-ephrinB2 complex, which consisted of a heterotetramer, crystals of the EphB4-ephrinB2 complex consist of a heterodimer. Previously, formation of ephrinB2-EphB2 tetramers was observed for a concentration range around 1 mM using size exclusion chromatography analysis (SEC), while analytical ultracentrifugation demonstrated that the EphB2-ephrinB2 complex was a heterodimer at concentrations in the low micromolar range (10). The SEC analysis of the of the present invention provides the EphB4-ephrinB2 complex in a concentration range up to 500 μM indicating that the EphB4-ephrinB2 complex exsists as a heterodimer (data not shown). The overall structure of the EphB4-ephrinB2 complex is similar to that of the EphB2-ephrinB2 complex, with an r.m.s. deviation of 5.0 Å over 316 equivalent Cα positions. Significant deviation is evident, however, throughout the structure of the loop regions compared with the EphB4-TNYL-RAW and EphB2-ephrinB2 structures, with r.m.s. deviations of 1.8 and 5.3 Å, respectively in the J-K loop. The ephrinB2 ligand deviates minimally between previously described apo and receptor-bound structures, shifting only 0.91 and 0.90 Å respectively (10, 17).  
         [0101]     EphB4-EphrinB2 Interface  
         [0102]     Although the overall shape of the EphB4-ephrinB2 interaction interface is in good agreement with that previously described in the EphB2-ephrinB2 structure, marked differences exist within the receptor loops that frame the ligand binding channel. The EphB4 J-K loop assumes a distinct position compared to previously described crystal structures, and is situated directly above the ligand G-H loop and 15 Å from the D-E loop ( FIG. 2 ). The corresponding J-K loop from the EphB2-ephrinB2 structure, on the other hand, is shifted 6.4 Å from the D-E loop, and therefore maintains a more compact binding cavity. In fact, the J-K loops differ in position by up to 10 Å from furthest positions between the two ephrinB2-bound complex structures. Not surprisingly, the J-K loop shows remarkable flexibility in each structure described, also shifting in position by up to 20 Å from furthest positions between the EphB4-TNYL-RAW structure and the EphB4-ephrinB2 structure. Furthermore, crystallization trials with the apo form of EphB4 failed to produce diffracting crystals, likely because of the inherent flexibility of the J-K and D-E loops. A feature unique to EphB4 is a three residue insert in the J-K loop, which is absent in all other Eph receptors. It has been speculated that this insert contributes to the ligand binding specificity inherent to the EphB4 receptor (35). Indeed, two of the three residues (Pro-151, Gly-152, Ala-153) form the tip of the J-K loop, and make contacts with the ligand: Pro-151 R(R. receptor; L, ligand) forms a hydrophobic contact with Phe-120L, while Gly-152R makes a main-chain to side-chain polar contact with Glu-152L. In addition, the G-H and D-E loops, which form two walls of the ligand binding cleft, also shift in order to accommodate the ligand. The G-H loop is shifted by over 4.5 Å between the EphB4 and EphB2-bound ephrinB2 structures, while the D-E loop only deviates by 1.5 Å between the two structures.  
         [0103]     The high affinity EphB4-ephrinB2 heterodimer is formed by insertion of the solvent exposed ligand G-H loop into the upper convex and hydrophobic surface of the EphB4 receptor, positioned above receptor strands E and M. Hydrophobic contacts drive receptor-ligand binding in this region. Ligand residues Phe-120, Pro-122, Trp-125 and Leu-127 participate in van der Waals interactions with receptor residues lining the receptor binding cavity in the D-E, G-H and J-K loops ( FIG. 4 ). Phe-120L forms hydrophobic interactions with Leu-95R (see below), Leu-100R, and Pro-101R, while Leu-124L interacts with Thr-147R from the receptor J-K loop. Meanwhile, Trp-125L extends to the surface of the receptor, in-between the J-K and G-H loops, participating in hydrophobic interactions with residues Leu-48R, Glu-50R, Val-159R, Leu-188R, and Ala-186R. In addition, Pro-122L, similar to all previous crystal structures, maintains its position by participating in a direct interaction with the receptor Cys61-Cys-184 disulfide bridge. Few polar contacts are formed at the receptor-ligand dimer interface. Ser-121 L forms a side-chain side-chain hydrogen bond with Glu-59R as well as a main-chain side-chain hydrogen bond with Lys-149R, while Asn-123L forms a hydrogen bond with the main-chain oxygen of Leu-48R. Additionally, Lys-149R extends to the body of the ephrinB2 G-H loop, forming side-chain side-chain hydrogen bonds with Glu-128L, and side-chain main-chain hydrogen bonds with Ser-121L and Asn-123L, wich are both part of the high affinity ligand FSPN sequence ( FIG. 3 ). The introduction of this new interaction at the EphB4-ephrinB2 interface is certain to contribute to the high affinity of this receptor-ligand complex.  
         [0104]     Similar to the EphB2-ephrinB2 structure, a second portion of the high affinity heterodimerization interface exists immediately adjacent to the ligand binding cavity, formed by ligand strands C, G. and F. and receptor strands B-C, E, and D. This region of the complex deviates minimally from the corresponding structure of in the EphB2-ephrinB2 complex, with a maximum of 2.1 Å from furthest atoms, and is predominantly characterized by backbone-backbone, backbone-sidechain, and sidechain sidechain hydrogen bonds. In particular, sidechain-sidechain interactions between Glu-59R (Glu-68 in EphB2)-Gln-118L and Ser-121 L, Asp-29R (Glu-40 in EphB2)-Lys-112L, and Glu-43 (Glu-52, EphB2)-Lys 116L provide the binding potential characteristic of this low nanomolar interaction. Sidechain-mainchain interactions between Ser-55 and Lys-116L, and Glu-44R and Lys-60R complete the binding network in this region.  
         [0105]     EphB4 Specificity  
         [0106]     Sequence comparison and structural analysis of the EphB4 and EphB2 receptors suggested that one residue in EphB4 is particularly important in determining the specificity of the EphB4-ephrinB2 interaction: Leu-95. The corresponding residue in EphB2, Arg-103, is strictly conserved across both A and B subclasses, and deviates only in the EphB4 receptor. Arg-103R participates in hydrogen bonds with residues from the high affinity ephrin G-H loop, including Ser-121L and Glu-128L, and is situated in proximity to Phe-120L, a residue critical for receptor binding. However, superposition of Arg to Leu-95 in the EphB4-ephrinB2 structure suggests that a steric clash would result between an arginine at position 95R and Phe-120L. The corresponding Leu-95R, on the other hand, is able to form a 3.2 Å van der Waals interaction with Phe-120L due to its position within the ligand binding cavity. Thus, Arg-95R would also sterically clash with the phenylalanine from the TNYL-RAW peptide in the EphB4-TNYL-RAW structure (19), while the smaller Leu-95R forms favorable contacts with the peptide. Interestingly, the highly conserved Phe-120L is shifted in position by ˜90° as compared to previous complex structures (8, 10, 19) ( FIG. 5 ) and is buried within the hydrophobic cleft of the receptor, unlike its position in the EphB2-ephrinB2 complex structure, where it is directed towards the surface. In addition, the position of Arg-103R requires the J-K loop of the EphB2 receptor to extend away from the ligand G-H loop and towards the receptor D-E loop to avoid steric interference with residues lining the ephrin-B2 G-H loop. The smaller Leu-95R, together with the Phe-120L, allows the J-K loop of EphB4 to adopt a novel position directly above the ligand G-H loop.  
         [0107]     Biophysical Characterization of EphB4 Specificity: Enthalpic vs. Entropic Contributions  
         [0108]     A series of site-specific mutations was generated by changing residues lining the EphB4 G-H and J-K loops to the corresponding residues found in EphB2 (Table 3). The EphB4 mutants were rank-ordered based on their binding to fluorescently labeled Alexa-532-TNYL-RAW peptide. Fluorescence Polarization (FP) analysis corroborated the prediction that Leu-95 is a critical determinant for binding of the TNYL-RAW peptide because the Leu95Arg mutant did not exhibit significant binding of the peptide in our assay. EphB4 mutants Thr147Phe, Ala186Ser and Lys149Gln showed approximately 4-5 fold reduction in binding affinity of the fluorescently labeled peptide. The reduction in affinity due to mutation of these residues is consistent with what would be expected based on the structural information. A Thr-147-Phe mutation would impose steric constraints between the receptor J-K loop and the ephrinB2 G-H loop, as well as with Leu-95R due to the position of the receptor J-K loop. Interestingly, EphB4 possesses an alanine at position 186, which is conserved across the A-subclass while other B-subclass receptors have a conserved Ser. Ala-186R forms a van der Waals interaction with the main chain carbon of Asn-123 of the high affinity ligand G-H loop. A Ser at position 186 of EphB4 would cause a polar redistribution at the heterodimerization interface with ephrinB2 and result in the displacement of the receptor G-H loop due to a steric clash with Thr-93L and potential displacement of the ephrinB2 G-H loop. Finally, Lys-149R forms interactions at the dimer interface with ephrinB2 residues Ser-121L, Asn-123L and Gln-128L. Mutation to Gln should not result in steric interference with the ligand G-H loop, but could result in a slight readjustment of the J-K loop in order to accommodate the bulkier Gln side chain.  
         [0109]     Based on the structural information and preliminary binding characterization, two EphB4 mutants, Leu95Arg and Lys149Gln, were chosen for detailed thermodynamic analysis of their binding to both ephrinB2 and the TNYL-RAW peptide ligand using isothermal titration calorimetry (ITC). As reported previously, EphB4 binds to ephrinB2 with an affinity of 40 nM and a ΔH obs  of 3.3 kcal mol −1  (19). Mutation of EphB4 Lys-149 to Gln has no effect on the binding affinity or enthalpy of ephrinB2 binding (Table 4). In contrast, mutation of EphB4 Leu-95 to Arg reduces the binding affinity of ephrinB2 by nearly two orders of magnitude. Binding of ephrinB2 to all forms of EphB4 is endothermic, and the binding of ephrinB2 is more endothermic with the L95R mutation in EphB4 (5.2 kcal mol −1  versus 3.3 kcal mol −1  for wild-type EphB4). Preliminary experiments carried out in a buffer with different enthalpy of ionization showed a similar enthalpy change to that reported here. For example, binding of ephrinB2 to EphB4 (K149Q) results in a ΔH obs  of 3.9 (±0.1) kcal mol −1  in phosphate (ΔH ion =0.8 kcal mol −1 ) compared to the ΔH obs  of 3.7 (+0.2) kcal mol −1  value obtained in Tris (ΔH ion =11.34 kcal mol −1 ) (Table 4). Thus, the protonation/deprotonation is not coupled to ephrinB2 binding under the conditions of the ITC experiments.  
         [0110]     Binding of the TNYL-RAW peptide to the wild-type, Lys149Gln, and Leu95Arg forms of EphB4 was also monitored by ITC. TNYL-RAW binds to EphB4 with an affinity of 70 nM and a ΔH obs  of −14.7 kcal mol −1  (19). In contrast to the different effects of mutations in EphB4 on the interaction of EphB4 with ephrinB2, mutation of EphB4 of either Lys-149 to Gln or Leu-95 to Arg reduces the affinity of the EphB4-TNYL-RAW interaction (three-fold and 500-fold, respectively; Table 4). Binding of the TNYL-RAW peptide to all three forms of EphB4 is characterized by an exothermic enthalpy.  
         [0111]     Thus, thermodynamic analysis reveals that TNYL-RAW binding to the EphB4 ligand binding domain is an enthalpically driven process, while ephrinB2 binding to EphB4 is an entropically driven process. The differences in the binding thermodynamics are consistent with the available structural information. Burial of the hydrophobic ligand G-H loop within the hydrophobic receptor binding cleft could entropically drive the interaction through the release of water, increasing the solvent entropy. In addition, the ephrinB2 ligand G-H loop is quite rigid, both in apo and receptor-bound structures, minimizing massive conformational entropy losses. The small loss of conformational entropy counteracts the heterodimerization process by ordering the otherwise flexible receptor J-K, D-E, and G-H loops. Unlike ephrinB2, however, the free peptide ligand loses significant conformational degrees of freedom upon EphB4 binding, resulting in an entropy loss. This is compensated by an enthalpic gain due to the formation of favorable interactions, both polar and nonpolar, at the receptor-peptide interface.  
         [0112]     It should be noted that we produced the ephrinB2 extracellular domain in insect cells in a glycosylated form, while the ephrins used for previous crystal structure determinations were produced in  E. coli  and therefore not glycosylated. A conserved glycosylation site exists in ephrinB2 at residue Asn-39, in proximity of the low affinity tetramerization interface. Consistent with its possible glycosylation, Asn-39 is located near the surface of the protein and its side chain extends toward the surface of the complex. Although the carbohydrate was not observed in our electron density map, most likely because it was disordered, there is a theoretical possibility that a sugar at this location could interfere with the formation of receptor-ligand tetramers in the crystal lattice. However, previous reports have suggested that carbohydrate moieties would play more a favorable than an unfavorable role in tetramerization (36).  
       OTHER EMBODIMENTS  
       [0113]     The detailed description set-forth above is provided to aid those skilled in the art in practicing the present invention. However, the invention described and claimed herein is not to be limited in scope by the specific embodiments herein disclosed because these embodiments are intended as illustration of several aspects of the invention. Any equivalent embodiments are intended to be within the scope of this invention. Indeed, various modifications of the invention in addition to those shown and described herein will become apparent to those skilled in the art from the foregoing description which do not depart from the spirit or scope of the present inventive discovery. Such modifications are also intended to fall within the scope of the appended claims.  
       REFERENCES CITED  
       [0114]     Citation of a reference herein shall not be construed as an admission that such is prior art to the present invention. Specifically intended to be within the scope of the present invention, and incorporated herein by reference in its entirety, is the following publication: Chrencik, J. E., Brooun, A., Kraus, M. L., Recht, M. I., Kolatkar, A. R., Han, G. W., Seifert, J. M., Widmer, H., Auer, M., Kuhn, P. Structural and Biophysical Characterization of the EphB4-EphrinB2 Protein-Protein Interaction and Receptor Specificity. (2006) J. Biol. Chem. 281:28185-28192.  
         [0115]     Publications referred to herein include: 
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Technology Classification (CPC): 6