Compositions of hepatitis C virus NS5B polymerase and methods for crystallizing same

Abstract

The invention relates to the purification, crystallization of and structure of hepatitis C virus (HCV) NS5B RNA-dependent RNA polymerase. Also, crystallization conditions for NS5B are provided. Further, the atomic coordinates for the NS5B protein are disclosed. Examples of its use for the determination of the three-dimensional atomic structures of HCV NS5B or HCV NS5B in complex with substrates or substrate analogs or inhibitors are also provided.

Description

FIELD OF THE INVENTION

[0001] The present invention relates to compositions and crystals of a hepatitis C virus RNA dependent RNA polymerase called NS5B and to methods of producing such crystals. This invention relates to methods of using the structure coordinates of hepatitis C virus NS5B to solve the structure of homologous NS5B proteins or complexes containing the NS5B protein.

BACKGROUND OF THE INVENTION

[0002] Infection by hepatitis C virus (HCV) is a compelling human medical problem. HCV is recognized as the causative agent for most cases of non-A and non-B hepatitis, with an estimated human seroprevalence of 1% globally [Choo, et al., Science, 244:359-362 (1989); Kuo, et al., Science, 244:362-364 (1989); Purcell, FEMS Microbiology Reviews; 14:181-192 (1994); Van der Poel. Current Studies in Hematology and Blood Transfusion, H. W. Reesink, Ed., (Basel: Karger), pp. 137-163 (1994)]. Four million individuals may be infected in the United States alone [Alter, and Mast, Gastroenterol. Clin. North Am., 23:437-455 (1994)].

[0003] Upon first exposure to HCV, only about 20% of infected individuals develop acute hepatitis and appear to resolve the infection spontaneously. In the most instances (.about.80%), however, the virus establishes a chronic infection that persists for decades [Iwarson, FEMS Microbiology Reviews, 14: 201-204 (1994)]. This usually results in recurrent and progressively worsening liver inflammation, which often leads to more severe disease states such as cirrhosis and hepatocellular carcinoma [Kew, FEMS Microbiology Reviews, 14: 211-220 (1994); Saito, et al., Proc. Natl. Acad. Sci. USA 87: 6547-6549 (1990)].

[0004] The HCV genome encodes a polyprotein of approximately 3000 amino acids [Choo, et al. Proc. Natl. Acad. Sci. USA, 88: 2451-2455 (1991); Kato, et al., Proc. Natl. Acad. Sci. USA, 87: 9524-9528 (1990); Takamizawa, et al., J. Virol., 65:1105-113 (1991)]. The HCV non-structural (NS) proteins provide catalytic machinery for viral replication. The NS proteins are derived by proteolytic cleavage of the polyprotein [Bartenschlager, et al., J. Virol., 67: 3835-3844 (1993); Grakoui, et al., J. Virol, 67: 2832-2843 (1993); Grakoui, et al., J. Virol., 67:1385-1395 (1993); Tomei, et al., J. Virol., 67:4017-4026 (1993)].

[0005] Until recently, the only therapy available for treating chronic HCV infection was interferon-.alpha.(IFN-.alpha.). However, not all patients are responsive to IFN-.alpha. treatment. While combination therapy of IFN-.alpha. and ribavirin has significantly improved the clinical outcome, a need exists for more effective methods of treatment.

[0006] The NS5B RNA dependent RNA polymerase is considered a valuable target for antiviral agents. However, drug discovery efforts directed towards the NS5B protein have been hampered by the lack of structural information about NS5B. Such structural information would provide valuable information for discovery of HCV NS5B polymerase inhibitors. However, efforts to determine the structure of HCV NS5B polymerase have been hampered by difficulties in obtaining sufficient quantities of pure active enzyme and by poor solubility of the enzyme. There have been no crystals reported of any NS5B polymerase polypeptide. Thus, x-ray crystallographic analysis of such proteins has not previously been available.

SUMMARY OF THE INVENTION

[0007] The present invention addresses this need by providing, for the first time, compositions comprising a crystallized hepatitis C virus (HCV) NS5B polypeptide. Methods for obtaining purified and crystallized NS5B polypeptide are also provided. Such methods comprise solubilizing a NS5B polypeptide in a solution containing a protein stabilizing agent, subjecting the NS5B preparation to cation exchange chromatography, and allowing crystals to form in a precipitant solution containing a protein stabilizing agent and polyethylene glycol under conditions in which crystallization occurs.

[0008] The invention also provides a machine-readable data storage medium encoded with the structural coordinates of a NS5B polypeptide or a homologue thereof. Such a homologue contains backbone atoms having a root mean square deviation of equivalent C.alpha. atoms of less than 3.0 .ANG. when compared to the NS5B polypeptide.

[0009] The invention also provides a method for determining at least a portion of the three-dimensional structure of molecules or molecular complexes which contain at least some structurally similar features to a HCV NS5B polypeptide.

[0010] Still another aspect of the present invention comprises a method of selecting or optimizing a potential ligand or inhibitor by performing drug design with a three-dimensional structure determined for the crystal, preferably in conjunction with computer modeling. The potential ligand or inhibitor is then contacted with the NS5B polypeptide and the binding thereof is detected. If the ligand is a potential inhibitor of NS5B activity, the candidate drug may then be contacted with NS5B and the inhibition of its activity can be measured.

[0011] In another embodiment of the invention, a method of obtaining structural information concerning a molecular complex of unknown structure by using the structure coordinates set forth in Table 1 is provided. Such a method comprises the steps of: generating x-ray diffraction data from a crystal of said complex, and applying crystallographic phases derived from at least a portion of the structure coordinates set forth in Table 1 to said x-ray diffraction pattern to generate a three-dimensional electron density map of at least a portion of the unknown structure.

BRIEF DESCRIPTION OF THE FIGURE

[0012] FIG. 1(a) depicts the motif organization of NS5B.

[0013] FIG. 1(b) depicts a schematic diagram of NS5B polymerase.

DETAILED DESCRIPTION OF THE INVENTION

[0014] In order that the invention described herein may be more fully understood, the following detailed description is set forth. All references cited herein are incorporated in their entirety by reference.

[0015] The present invention provides, for the first time, crystallizable compositions comprising a HCV NS5B polymerase polypeptide. Thus, one embodiment of this invention provides a composition comprising a crystalline hepatitis C virus NS5B polypeptide.

[0016] Another embodiment of the invention provides a NS5B protein whose sequence is more similar to various HCV genotypes and subtypes, particularly at amino acid positions 335, 344 and 550 of SEQ ID NO: 1. Preferred amino acids at these positions are valine, alanine and glutamine respectively, while the published sequence (GenBank Accession No. 130458) of the BK isolate has threonine, valine and arginine at the corresponding positions.

[0017] Yet another embodiment of this invention provides methods of using NS5B polypeptides to grow a crystal containing such polypeptides. One such method comprises solubilizing a NS5B protein preparation in a solution containing a protein stabilizing agent; subjecting the NS5B protein preparation to cation exchange chromatography in a buffer containing glycine; and allowing crystals to form in the presence of a precipitant containing a protein stabilizing agent, a salt and polyethylene glycol under conditions in which crystallization occurs. Preferably, such a crystal effectively diffracts x-rays for the determination of the atomic coordinates of the protein to a resolution of greater than 4.0 .ANG.ngstroms. More preferably, the crystal effectively diffracts x-rays for the determination of the atomic coordinates of the protein to a resolution of greater than 2.8 .ANG.ngstroms. In a most preferred embodiment, the crystal effectively diffracts x-rays for the determination of the atomic coordinates of the protein to a resolution of greater than 2.2 .ANG.ngstroms.

[0018] As used herein, the terms "HCV NS5B" and "NS5B" refers to the hepatitis C virus non-structural 5B protein as defined in Grakoui, et al., J. Virol. 67(3):1385-1395 (1993). See also Simons et al., Proc. Natl. Acad. Sci. USA 92(8): 3401-3405 (1995).

[0019] HCV "NS5B polypeptides" are polypeptides which have RNA dependent RNA polymerase-like domains similar to the naturally-occurring HCV NS5B. It also includes HCV NS5B and polypeptide fragments of NS5B having polymerase functionalities. These polypeptides also include polypeptides that differ from the NS5B polymerase by having amino acid deletions, substitutions, and additions. NS5B polypeptides may be derived from various HCV genotypes and subtypes known in the art.

[0020] The NS5B polypeptide may be produced by any well-known method, including synthetic methods, such as solid phase, liquid phase and combination solid/liquid phase syntheses; recombinant DNA methods, including cDNA cloning, optionally combined with site-directed mutagenesis; and/or purification of the natural products, optionally combined with enzymatic or chemical cleavage methods to produce NS5B or fragments thereof.

[0021] Various truncated forms of NS5B are within the scope of the invention and may enhance the solubility of the NS5B protein. A preferred truncation comprises a truncation of a stretch of amino acids in the carboxy terminal region of the protein, preferably containing hydrophobic amino acids. Most preferably, such a truncation includes the four leucine residues in the C-terminal region of NS5B. Truncations of 12-70 amino acids are preferred [Ferrari et al., J. Virol. 73:1649-1654 (1999)]. Optionally, it may also be desirable to add amino acids onto the NS5B protein or truncated NS5B. One preferred addition is a polyhistidine tag, 5-20 amino acids in length. Most preferred is a 6 amino acid histidine tag added to the amino-terminus of the NS5B protein or truncated NS5B. Preferably, the NS5B protein has a histidine tag at its amino-terminus for use in purifying the protein.

[0022] In one embodiment of the invention, the NS5B polymerase polypeptide is tNS5B, a recombinantly-produced truncated hepatitis C virus RNA dependent RNA polymerase polypeptide. The tNS5B protein contains both a 21 amino acid deletion at the carboxy-terminus and a 6 amino acid histidine tag at the amino-terminus [Ferrari, et al., J. Virol. 73:1649-1654 (1999)].

[0023] One aspect of the present invention relates to a method of purifying the NS5B polypeptides and obtaining NS5B crystals. Preferably, the NS5B polypeptide may be produced recombinantly in E. coli and initial purification may be accomplished by nickel chelate chromatography, as previously described [Petty (1996) "Metal chelate affinity chromatography" in: Ausubel, et al., eds. Current Protocols in Molecular Biol., Vol. 2 New York, John Wiley and Sons]. This NS5B preparation is transferred into a solution containing a protein stabilizing agent and glycine. Next, the preparation is applied to a cation exchange resin and subjected to chromatography, eluting the protein with a salt gradient. The resulting solution preferably contains a protein stabilizing agent, a salt, a buffering agent and optionally a reducing agent or an oxygen scavenger. Examples of suitable reducing agents are dithiothreitol (DTT), dithioerythritol (DET) and .beta.-mercaptoethanol. If necessary, the reducing agent is present in the buffered solution at a concentration of about 5 mM and is preferably DTT. The pH of the buffering agent may range from 4.5 to 8, preferably between pH 7 and 8.

[0024] Although other solution components can be substituted for the above described components, the protein stabilizing agent and salt appear to be important for the solubility of the NS5B protein preparation. Protein stabilizing agents include polyols, sugars, as well as amino acids and amino acid analogs. Some examples include erythritol, sorbitol, glycerol, fructose, trehalose, proline, .beta.-alanine, taurine and glycine betaine. These agents are sometimes referred to as cosmotropic agents and are well known in the art. [Jeruzalmi & Steitz, J. Mol. Biol. 274: 748-756 (1997)]. The concentration of such agents will vary depending upon the type of agent employed. For example, if glycerol is chosen, it is preferably provided in a concentration range from about 2 to about 20% (v/v), preferably about 10% (v/v), while a salt may be provided in a concentration of above about 150 mM. Many salts are routinely used in the art and may be variously used in the method of the present invention.

[0025] Glycine in the buffer solution maintains the solubility of the NS5B preparation in the absence of salt and allows further purification by cation exchange chromatography. Various types of cation exchange chromatography may be employed in this purification step. See Scopes, Protein Purification: Principles and Practice, Third ed., Springer-Verlag, New York (1994). Glycine can range in concentration from 500-1500 mM, preferably one molar. Glycine is preferably removed after cation exchange chromatography.

[0026] Compounds known as "precipitants" are often used to decrease the solubility of the polypeptide in a concentrated solution. Alternatively, "precipitants" can be changes in physical or chemical parameters which decrease polypeptide solubility, including temperature, pH and salt concentrations. Precipitants induce crystallization by forming an energetically unfavorable precipitant-depleted layer around the polypeptide molecules. To minimize the relative amount of this depletion layer, the polypeptides form associations and ultimately crystals as explained in Weber, Advances in Protein Chemistry 41:1-36 (1991) which is incorporated by reference. In addition to precipitants, other materials are sometimes added to the polypeptide crystallization solution. These include buffers to adjust the pH of the solution (and hence surface charge on the peptide) and salts to reduce the solubility of the polypeptide. Various precipitants are known in the art and include the following: ammonium sulfate, ethanol, 3-ethyl-2,4 pentanediol; and many of the polyglycols, such as polyethylene glycol. A suitable precipitant for crystallization of NS5B polypeptides is polyethylene glycol (PEG), which combines some of the characteristics of the salts and other organic precipitants.

[0027] Crystallization may be accomplished by using any of the known methods in the art [Gieg, et al., Acta Crystallogr. D50: 339-350 (1994); McPherson, Eur. J. Biochem. 189: 1-23 (1990)]. Such techniques include microbatch, hanging drop, seeding and dialysis. Preferably, hanging-drop vapor diffusion [McPherson, J. Biol. Chem. 251: 6300-6303 (1976)] or microbatch methods [Chayen, Structure 5: 1269-1274 (1997)] are used. In each of these methods, it is important to promote continued crystal growth after nucleation by maintaining a supersaturated solution. In the microbatch method, polypeptide is mixed with precipitants to achieve supersaturation, the vessel is sealed and set aside until crystals appear. In the dialysis method, polypeptide is retained in a sealed dialysis membrane which is placed into a solution containing precipitant. Equilibration across the membrane increases the precipitant concentration thereby causing the polypeptide to reach supersaturation levels.

[0028] It is desirable to use a NS5B protein preparation having a concentration of at least 1 mg/mL and preferably less than 65 mg/mL. Crystallization may be best achieved in a precipitant solution containing polyethylene glycol 1000-20,000 (PEG; average molecular weight ranging from 1000-20,000 Da), preferably 4000-5000 with concentrations ranging from 15-25% (w/v). It is further desirable to avoid the use of extremely high and low molecular weight PEGs. It may also be desirable to include a protein stabilizing agent. If glycerol is chosen as the protein stabilizing agent, it is preferably provided at concentration ranging from 0.5 to 20% (v/v). A suitable salt, such as sodium chloride, may also be desirable in the precipitant solution, preferably in concentration ranging from 1 to 1000 mM. The precipitant is preferably buffered to a pH of about 4.5 to 8.0. Most preferred is a buffer solution at a pH of about 5 to 6. Specific buffers useful in the precipitant solution may vary and are well-known in the art [Scopes, Protein Purification: Principles and Practice, Third ed., (1994) Springer-Verlag, New York]. Examples of useful buffers include but are not limited to Tris, MES and acetate. Crystals routinely grow in a wide range of temperature. It is however preferred that crystals form at temperatures between 4.degree. C. and 26.degree. C., and more preferably at 20.degree. C. to 22.degree. C.

[0029] The crystals of the present invention have a wide range of uses. For example, high quality crystals are suitable for x-ray or neutron diffraction analysis to determine the three dimensional structure of NS5B polypeptides and in particular to assist in the identification of the protein's active and effector sites. Knowledge of these sites and solvent accessible residues allow rational design and construction of agonists and antagonists for NS5B polypeptides.

[0030] In addition, crystallization itself can be used as a purification method. In some instances, a polypeptide or protein crystallizes from a heterogeneous mixture into crystals. Isolation of such crystals by filtration and/or centrifugation, followed by redissolving the polypeptide affords a purified solution suitable for use in growing the high-quality crystals necessary for diffraction analysis.

[0031] Once a crystal of the present invention is grown, x-ray diffraction data can be collected. One method for determining structure uses synchrotron radiation, under standard cryogenic conditions for such x-ray diffraction data collection. However alternative methods may also be used. For example, crystals can be characterized by using x-rays produced in a conventional source (such as a sealed tube or a rotating anode), optionally under cryogenic conditions. Methods of characterization include, but are not limited to, precession photography, oscillation photography and diffractometer data collection.

[0032] Advantageously, the crystallizable compositions provided by this invention are amenable to x-ray crystallography. Thus, this invention also provides the three-dimensional structure of an HCV NS5B polypeptide at 1.9 .ANG. resolution. Importantly, this has provided for the first time, detailed information about the shape and structure of the NS5B polymerase protein.

[0033] The three-dimensional structure of the HCV NS5B polymerase of this invention is defined by a set of structure coordinates as set forth in Table 1. The term "structure coordinates" refers to Cartesian coordinates derived from mathematical equations related to the patterns obtained on diffraction of a beam of x-rays by the atoms (scattering centers) of NS5B polymerase in crystal form. The diffraction data are used to calculate electron density maps and to establish the positions of the individual atoms of the NS5B enzyme.

[0034] Those of skill in the art will understand that a set of structure coordinates for an enzyme or an enzyme-complex or a portion thereof, is a relative set of points that define a shape in three dimensions. Thus, it is possible that an entirely different set of coordinates could define a similar or identical shape. Moreover, slight variations in the individual coordinates will have little effect on overall shape.

[0035] The variations in coordinates discussed above may be generated because of mathematical manipulations of the structure coordinates. For example, the structure coordinates set forth in Table 1 can be manipulated by crystallographic permutations of the structure coordinates, fractionalization of the structure coordinates, additions, subtractions, rotations or translations to sets of the structure coordinates or any combinations of the above.

[0036] Alternatively, modifications in the crystal structure due to mutations, additions, substitutions, and/or deletions of amino acids, or other changes in any of the components that make up the crystal may also account for variations in structure coordinates. If such variations are within an acceptable standard error as compared to the original coordinates, the resulting three-dimensional shape is considered to be the same.

[0037] Various computational analyses are therefore necessary to determine whether a molecular complex or a portion thereof is sufficiently similar to all or parts of the NS5B polypeptide structure described above as to be considered the same. Such analyses may be carried out in current software applications, such as the Molecular Similarity application of QUANTA (Molecular Simulations Inc., San Diego, Calif.) version 4.1, and as described in the accompanying User's Guide.

[0038] The Molecular Similarity application permits comparisons between different structures, different conformations of the same structure, and different parts of the same structure. The procedure used in Molecular Similarity to compare structures is divided into four steps: 1) input the structures to be compared; 2) define the atom equivalences in these structures; 3) perform a fitting operation; and 4) analyze the results.

[0039] Each structure is identified by a name. One structure is identified as the target (i.e., the fixed structure); all remaining structures are working structures (i.e., moving structures). Since atom equivalency within QUANTA (Molecular Simulations Inc., San Diego, Calif.) is defined by user input, for the purpose of this invention, equivalent atoms are defined as protein alpha carbon atoms (C.alpha.). When the C.alpha. atoms of the working structure are superimposed on the relevant reference C.alpha. atoms described by structure coordinates listed in Table 1 with an RMSD of less than 3 .ANG., the two structures are considered identical. More preferably, the root mean square deviation is less than 2.0 .ANG..

[0040] The term "root mean square deviation" or "RMSD" means the square root of the arithmetic mean of the squares of the deviations from the mean. It is a way to express the deviation or variation from a trend or object. For purposes of this invention, the "root mean square deviation" defines the variation in the alpha carbon of a protein or protein complex from the relevant portion of the alpha carbon of the NS5B polypeptide as defined by the structure coordinates described herein.

[0041] Thus, in accordance with the present invention, the structure coordinates of the NS5B polypeptide and portions thereof are stored in a machine-readable storage medium. Such data may be used for a variety of purposes, such as drug discovery and x-ray crystallographic analysis of a protein crystal.

[0042] Accordingly, one aspect of this invention provides a machine-readable data storage medium comprising a data storage material encoded with the structure coordinates set forth in Table 1.

[0043] A computer system useful in reading the machine readable data storage medium includes a computer comprising a central processing unit ("CPU") and a memory storage device. In general, the computer system may be any computer with an operating system such as MS-DOS, PC-DOS, Windows, OS/2, Unix, Unix variant or MacOS. Particularly preferred computer systems are the Silicon Graphics Octane workstation or Compaq AlphaServer DS20. Other hardware systems and software packages will be known to those skilled in the art.

[0044] Input hardware coupled to the computer system by input lines, may be implemented in a variety of ways. Machine-readable data of this invention may be inputted via the use of a modem or modems connected by a telephone line or a dedicated data line. Alternatively or additionally, the input hardware may comprise CD-ROM drives or disk drives. A keyboard or optical scanner may also be used as an input device.

[0045] Output hardware, coupled to the computer system by output lines, may similarly be implemented by conventional devices. By way of example, output hardware may include a display terminal for displaying a graphical representation of a binding pocket of this invention using a program such as INSIGHT (Molecular Simulations Inc., San Diego, Calif.) as described herein. Output hardware might also include a printer, so that hard copy output may be produced, or a disk drive, to store system output for later use.

[0046] In operation, the CPU coordinates the use of the various input and output devices, coordinates data accesses from mass storage and accesses to and from working memory, and determines the sequence of data processing steps. A number of programs may be used to process the machine-readable data of this invention. Such programs are discussed in reference to the computational methods of drug discovery as described herein. Specific references to components of the computer system are included as appropriate throughout the following description of the data storage medium.

[0047] A magnetic data storage medium can be encoded with a machine-readable data by a computer system as described above. Storage medium may be, for example, a conventional floppy diskette or hard disk, having a suitable substrate, which may be conventional, and a suitable coating, which may be conventional, on one or both sides, containing magnetic domains whose polarity or orientation can be altered magnetically. Storage medium may also have an opening for receiving the spindle of a disk drive or other data storage device. Alternatively, an optically-readable data storage medium can be encoded with such a machine-readable data, or a set of instructions. Medium can be a conventional compact disk read only memory (CD-ROM) or a rewritable medium such as a magneto-optical disk which is optically readable and magneto-optically writable.

[0048] In the case of CD-ROM, as is well known, a coating is reflective and is impressed with a plurality of pits to encode the machine-readable data. The arrangement of pits is read by reflecting laser light off the surface of the coating. A protective coating, which preferably is substantially transparent, is provided on top of the coating.

[0049] In the case of a magneto-optical disk, as is well known, the coating has no pits, but has a plurality of magnetic domains whose polarity or orientation can be changed magnetically when heated above a certain temperature, as by a laser. The orientation of the domains can be read by measuring the polarization of laser light reflected from the coating. The arrangement of the domains encodes the data as described above.

[0050] The present invention permits the use of structure-based drug design techniques to design, select, and optionally optimize the structure of chemical entities, including inhibitory compounds that are capable of binding to HCV NS5B polymerase or any portion thereof. Also, de novo drug design methods with iterative structure-based drug design methods can be used to develop inhibitors from the crystal structure of the present invention.

[0051] One particularly useful drug design technique enabled by this invention is structure-based drug design. Structure-based drug design is a method for optimizing associations between a protein and a compound by determining and evaluating the three-dimensional structures of one or more sets of protein/compound complexes.

[0052] Those skilled in the art will realize that association of natural ligands or substrates with the binding pockets of their corresponding receptors or enzymes is the basis of many biological mechanisms of action. The term "binding pocket", as used herein, refers to any region of a molecule or molecular complex, that, as a result of its shape, favorably associates with another chemical entity or compound. Similarly, drugs may exert their biological effects through association with the binding pockets of receptors and enzymes. Such association may occur with all or a subset of the binding pockets. An understanding of such associations will help lead to the design of drugs having more favorable associations with the target enzyme, and thus, improved biological effects. Therefore, this information is valuable in designing enzyme inhibitors, such as inhibitors of HCV NS5B polypeptides.

[0053] In iterative structure-based drug design, crystals of a series of protein/compound complexes are obtained and then the three-dimensional structures of each complex are solved. Such an approach provides insight into the association between the proteins and compounds of each complex. This is accomplished by selecting a compound with inhibitory activity, obtaining crystals of the polypeptide in complex with this compound, solving the three-dimensional structure of the complex, and comparing the polypeptide/compound associations between the new structure and previously solved structure(s). By observing how changes in the compound affect the protein/compound associations, these associations may be optimized.

[0054] In some cases, iterative structure-based drug design is carried out by forming successive protein-compound complexes and then crystallizing each new complex. Alternatively, a pre-formed protein crystal is soaked in the presence of an inhibitor, thereby forming a protein/compound complex and obviating the need to crystallize each individual protein/compound complex. Advantageously, the HCV NS5B polymerase crystals provided by this invention may be soaked in the presence of a compound or compounds, such as NS5B inhibitors, substrates or other ligands to provide NS5B polypeptide compound crystal complexes. As used herein, the term "soaked" refers to a process in which the crystal is transferred to a solution containing the compound of interest or the compound of interest is added to the solution containing the crystal.

[0055] The structure coordinates set forth in Table 1 can also be used to aid in obtaining structural information about another crystallized molecule or molecular complex. This may be achieved by any of a number of well-known techniques, including molecular replacement.

[0056] The structure coordinates set forth in Table 1 can also be used for determining at least a portion of the three-dimensional structure of molecules or molecular complexes which contain at least some structurally similar features to HCV NS5B. In particular, structural information about another crystallized molecule or molecular complex may be obtained using well-known techniques, including molecular replacement.

[0057] Therefore, another aspect of this invention provides a method of utilizing molecular replacement to obtain structural information about a crystallized molecule or molecular complex whose structure is unknown comprising the steps of:

[0058] a) generating an x-ray diffraction pattern from said crystallized molecule or molecular complex; and

[0059] b) applying crystallographic phases derived from at least a portion of the structure coordinates set forth in Table 1 to the x-ray diffraction pattern to generate a three-dimensional electron density map of at least a portion of the molecule or molecular complex whose structure is unknown.

[0060] Once the structure coordinates of a protein crystal have been determined, they are useful in solving the structures of other crystals. In addition, the structures of NS5B complexes can be determined from the structure coordinates of the present invention. For example, complexes may be crystallized and their structure elucidated using such methods as difference Fourier or molecular replacement. NS5B complexes suitable for such analysis include, for example, NS5B in complex with an oligonucleotide template/primer duplex (i.e. substrate), wherein the duplex may have a single-stranded overhang of one or both strands on either or both ends of the oligonucleotide. Another example complex is NS5B complexed with a nucleotide triphosphate (i.e. substrate) or analog thereof. Most preferred is NS5B complexed with inhibitors such as nucleotide analogs, non-nucleotide inhibitors or inhibitors unrelated to substrate molecules. Yet another NS5B complex suitable for structure determination using the structure coordinates of NS5B is NS5B in complex with other members of the putative replicase complex, such as HCV NS3 protein, NS3 helicase domain, NS3 protease domain or other HCV proteins. A further NS5B complex suitable for structure determination is NS5B in complex with one or more cellular host factors (Cf. thioredoxin and T7 DNA polymerase) [Doubli et al., Nature 391: 251-258 (1998)]. Suitable complexes of NS5B may contain several other molecules or combinations of the above described complexes.

[0061] Preferably, the crystallized molecule or molecular complex comprises a NS5B polypeptide. More preferably, the crystallized molecule or molecular complex is obtained by soaking a crystal of this invention in a solution. By using molecular replacement, all or part of the structure coordinates of the NS5B polymerase provided by this invention (and set forth in Table 1) can be used to determine the structure of a crystallized molecule or molecular complex whose structure is unknown more quickly and efficiently than attempting to determine such information ab initio.

[0062] Molecular replacement provides an accurate estimation of the phases for an unknown structure. Phases are a factor, in equations used to solve crystal structures, that can not be measured experimentally. Obtaining accurate values for the phases, by methods other than molecular replacement, is a time-consuming process. However, when the crystal structure of a protein containing at least a homologous portion has been solved, the phases from the known structure may provide a satisfactory initial estimate of the phases for the unknown structure.

[0063] Thus, this method involves generating a preliminary model of a molecule or molecular complex whose structure coordinates are unknown, by orienting and positioning the relevant portion of the NS5B polymerase according to Table 1 within the unit cell of the crystal of the unknown molecule or molecular complex so as best to account for the observed x-ray diffraction pattern amplitudes to generate an electron density map of the structure whose coordinates are unknown. This, in turn, can be subjected to any well-known model building and structure refinement technique to provide a final, accurate structure of the unknown crystallized molecule or molecular complex [Lattman, "Use of the Rotation and Translation Functions", in Meth. Enzymol., 115: 55-77 (1985); Rossman, ed., "The Molecular Replacement Method", Int. Sci. Rev. Ser., No. 13, Gordon & Breach, New York (1972)].

[0064] Phase information from the structure coordinates of the present invention may be used to elucidate the structure of other crystals. For example, NS5B molecules in complex with other atoms or molecules, as described above, including complexes containing a heavy atom substructure from which useful phasing information may be extracted. Such complexes include, for example, those containing sulfur atoms of the endogenous cysteine and methionine amino acids as well as any atoms incorporated into, soaked into or cocrystallized within the crystal lattice. Other structures which can be elucidated using the phase information of the present invention include for example other RNA-dependent RNA polymerases (RdRps) of sufficient three-dimensional structure similarity to HCV NS5B as to be solved using molecular replacement. Examples of such RdRps include but are not limited to RdRp from bovine viral diarrhea virus, RdRp from yellow fever virus and RdRp from Dengue virus. Also, RdRps in a complex with a small molecule substrate, inhibitor, intermediate, transition state analog, product or analog of any of these may also be solved using phase information contained in the present invention. Other complexes whose structure can be elucidated from the phase information of the present invention include an RdRp in a complex with a macromolecule such as a template/primer substrate or host elongation factor, such as T7 DdDp/thioredoxin, or with a transcription inhibitor, such as T7 DdRp/T7 lysozyme, or with another HCV protein, such as NS3 protein, NS3 helicase or NS3 protease for example. Complexes containing a combination of the above molecules may also be solved using phase information of the present invention.

[0065] The structure of any portion of any crystallized molecule or molecular complex that is sufficiently homologous to any portion of the NS5B polymerase can be solved by this method. The difference Fourier method simply calculates an electron density map using phases calculated from the structure coordinates and observed diffraction amplitudes from a crystal of an unknown structure. This well-known method is often used to solve structures of protein/ligand complexes where the ligand is small and does not affect the crystal form significantly.

[0066] In a preferred embodiment, the method of molecular replacement is utilized to obtain structural information about a molecule wherein the molecule comprises a NS5B polypeptide or variant or complex thereof. Preferably the NS5B polypeptide comprises tNS5B or homologues thereof.

[0067] The structure coordinates of NS5B polymerase provided by this invention are particularly useful in solving the structure of other crystal forms of NS5B polypeptides.

[0068] The structure coordinates are also particularly useful to solve the structure of crystals of NS5B polypeptides, particularly tNS5B and polypeptides related in structure to NS5B. This approach enables the determination of the optimal sites for interaction between chemical entities, including interaction of candidate NS5B inhibitors with NS5B.

[0069] All of the complexes referred to above may be studied using well-known x-ray diffraction techniques may be refined versus x-ray data to 3 .ANG. resolution or better, to an R.sub.free value of about 0.40 or less using computer software, such as X-PLOR [Yale University, .COPYRGT.1992, distributed by Molecular Simulations, Inc.; see e.g., Blundell & Johnson, supra; Meth, Enzymol., vol. 114 & 115, H. W. Wyckoff et al., eds., Academic Press (1985)]. This information may thus be used to optimize known NS5B inhibitors, and to design new NS5B inhibitors.

[0070] In order that this invention be more fully understood, the following examples are set forth. These examples are for the illustrative purposes only and are not to be construed as limiting the scope of this invention in any way.

EXAMPLE 1

Construction of tNS5B

[0071] The amino acid sequence of NS5B (BK) was compared to 16 NS5B proteins from different genotypes and subtypes. Four isolates represent genotype 1 subtype a (HCV-1a) and five are from HCV-1b. The rest are from HCV-2a, 2b, 3a, 3b, 4a, 5a and 6a. Two substitutions were made to the NS5B (BK) sequence, one "T" to "V" at position 335, the other "V" to "A" at position 344 numbered according to SEQ ID NO: 1. The NS5B protein contains an additional change from the published NS5B (BK) sequence (GenBank Accession No. 130458), namely, an "R" to "Q" at position 550 numbered according to SEQ ID NO: 1. This NS5B protein has an amino acid sequence more similar than the published NS5B sequence to the other genotypes analyzed.

[0072] To make these substitutions, site-directed mutagenesis using the "Quick Change" mutagenesis kit (Stratagene, Calif.) was performed. The resulting clone was verified for correctness by direct sequencing. This NS5B construct was subcloned into pET-21b (Novagen, Wis.) between NheI and BamHI sites. Additional codons were engineered at the N-terminus (coding for a polyhistidine tag, MASHHHHHH, and replacing the native amino acids "SM" at the N-terminus of NS5B) to facilitate the cloning and purification. The C-terminal 21 amino acids were deleted to improve the solubility of NS5B. The sequence of the modified NS5B (designated as His-NS5B.DELTA.CT21) is set forth as SEQ ID NO: 1.

EXAMPLE 2

Expression and Purification of tNS5B

[0073] Hepatitis C virus (HCV) NS5B RNA-dependent RNA polymerase (RdRp) was cloned, transformed into E. coli and purified as previously described using nickel chelate chromotography. The particular construct used in this Example is described above and incorporated a six histidine tag at the N-terminus and 21-residue truncation from the C-terminus. See also Ferrari et al., J. Virol. 73:1649-1654 (1999). HCV NS5B RdRp was further purified using cation exchange resin (Mono-S HR 16/10, (Amersham Pharmacia Biotech AB, Uppsala, Sweden)) after overnight dialysis into 10% (v/v) glycerol, and 1 M glycine pH 7.0. After gel filtration chromatography (HiPrep 16/60 Sephacryl S100 High Resolution (Amersham Pharmacia AB, Uppsala, Sweden)) into 10% (v/v) glycerol, 600 mM NaCl, 5 mM DTT and 10 mM Tris pH 7.5, recombinant HCV NS5B was concentrated to between 10 and 40 mg/mL. At this stage, the concentrated protein was stored at -80.degree. C. until needed.

EXAMPLE 3

Crystallization and Data Collection

[0074] Crystallization experiments were conducted using both hanging-drop vapor diffusion and microbatch methods using newly prepared or freshly-thawed protein. For vapor-diffusion experiments, 2 .mu.L of protein was mixed with an equal volume of precipitant solution, placed on the underside of a siliconized glass coverslip, and sealed in close proximity to 1 mL of the precipitant solution. For the microbatch experiments, 2 .mu.L of protein was mixed thoroughly with an equal volume of precipitant solution and dispensed beneath a layer of paraffin oil. The precipitant solution contained poly(ethylene)glycol 1000 to 20,000 (PEG; average MW ranging from 1000 to 20,000 Da) with concentrations ranging from 15 to 25% [(v/v) or (w/v)]. The precipitant solution also contained 10% (v/v) glycerol and concentrations of NaCl ranging from 0 to 600 mM NaCl, using various buffers between pH 4.5 and 7.0. These buffers included acetate, MES, and Tris. After incubation at temperatures between 4.degree. C. and 26.degree. C. for 24 h, small plate-like crystals formed. Crystals grew to terminal size within two weeks with dimensions up to 300.times.300.times.50 .mu.m. After transfer of the crystals to cryoprotectant containing a few percent more PEG than the crystallization medium and up to 30% (v/v) glycerol, the crystals could be either frozen directly in liquid propane for storage prior to diffraction data collection or frozen in a gaseous nitrogen stream immediately before diffraction data collection.

EXAMPLE 4

Protein Preparation, MAD Experiment and Phasing

[0075] In preparation for a multiwavelength anomalous diffraction (MAD) experiment for the purpose of obtaining experimental crystallographic phases, a suitable atom or set of atoms must be incorporated into the crystal lattice. It is essential that this atom have an absorption edge within the practical range of x-ray wavelengths used for diffraction data collection. Rather than absorption, fluorescence is conventionally measured. This atom or set of atoms may be added exogenously to the native protein molecule (by soaking or cocrystallization methods), incorporated synthetically or incorporated biosynthetically into the protein itself. We chose the last method by substituting selenomethionine into the protein for the native methionine. This was accomplished by inhibiting the expression system's pathway for methionine biosynthesis and adding a suitable amount of selenomethionine to the growth medium for incorporation into the overexpressed protein. One may also use an expression system which is auxotrophic for methionine and similarly provide selenomethionine in the growth medium. This process is described in Doublie [Doubli, Meth. Enz. 276: 523-530 (1997)].

[0076] The selenomethionine-incorporated HCV NS5B protein was purified and crystallized in the same manner as the wild-type (sulfur-containing methionine) enzyme.

[0077] A MAD experiment was performed at beamline 17-ID-B at the Advanced Photon Source at Argonne National Laboratory as described in Hendrickson and Ogata [Hendrickson & Ogata, Meth. Enz. 276: 494-523 (1997)]. Briefly, an x-ray fluorescence energy scan was collected from a Se-met NS5B crystal. Data from this scan were used to assign the fluorescence edge and peak to determine the precise wavelengths of x-ray radiation required for the experiment. Complete x-ray diffraction data sets were collected, using the inverse-beam method [Hendrickson & Ogata, Meth. Enz. 276: 494-523 (1997)], at the peak fluorescence (wavelength=0.979 .ANG.), at the fluorescence edge (0.980 .ANG.) and at a low-energy remote wavelength (1.032 .ANG.).

[0078] Unprocessed diffraction images were indexed and the diffraction intensities integrated using the HKL computer program package [Otwinowski & Minor, Meth. Enzymol. 276: 307-326 (1997)]. Integrated intensities were reduced to unique data (as amplitides) using the programs of the CCP4 package including SCALA and TRUNCATE [Bailey, Meth. Enzymol. 276: 307-326 (1994); Evans, Joint CP4 and ESF-EACBM Newsletter 33: 22-24 (1997); French & Wilson, Acta Crystallogr. A34: 517-525 (1978)].

[0079] The selenium atom substructure was deduced using the direct methods structure solution software Shake-and-Bake version 2.0 beta [Miller et al., Acta Crystallogr. A34: 517-525 (1993); Miller et al., J. Appl. Crystallogr. 27: 613-621 (1994)] using the reduced, unique data from the peak fluorescence wavelength only.

[0080] The calculated sites for the 22 expected (based on amino acid sequence of the NS5B monomer and the anticipation of two NS5B monomers per asymmetric unit, which is based on calculation of the Matthews coefficient and other crystallographic analyses [Matthews, J. Mol. Biol. 33: 491-497 (1968)]) were then refined and experimental MAD phases calculated using the software SHARP [de La Fortelle & Bricogne, Meth. Enzymol. 276: 472-494 (1996)]. Subsequent density modification using the program SOLOMON [Abrahams & Leslie, Acta Crystallogr. D52: 30-42 (1996)] resulted in an interpretable electron density map.

EXAMPLE 5

Model Building and Refinement

[0081] After the polypeptide backbone was fit into the experimental electron density using the software O [Jones et al., Acta Crystallogr. A47: 110-119 (1991)], amino acid side chains were fit into electron density and the HCV NS5B primary sequence was registered onto the three dimensional polypeptide trace. After an initial cycle of manual fitting, the three dimensional coordinates were subjected to coordinate and B-factor refinement using simulated-annealing techniques implemented in the program X-PLOR [Brunger et al., Acta Crystallogr A 46: 585-93 (1990); Karplus et al., Cold Spring Harb Symp Quant Biol 52: 381-90 (1987)]. Iterative cycles of manual rebuilding, placement of solvent molecules, and refinement followed until convergence of the free R-factor to 0.30 [Kleywegt & Brunger, Structure 4:897-904 (1996); Kleywegt & Jones, Structure 3: 535-40 (1995)]. The stereochemical quality of the model was checked and verified at each cycle with the aid of the programs PROCHECK [Laskowski et al., J. Appl. Crystallogr. 26: 283-291 (1993)] and WHATIF [Hooft et al., Nature 381: 272 (1996)].

[0082] Crystals contain two HCV NS5B monomers per asymmetric unit and belong to space group P2.sub.12.sub.12.sub.1 with unit cell dimensions 86.times.105.times.126 .ANG.. These crystals diffract to at least 1.9 .ANG. resolution. A refined model of HCV NS5B RdRp was produced using data collected from a selenomethionine-incorporated protein. This three-dimensional atomic model contains greater than 95% of the expected scattering matter in the crystal and may be used to solve, using difference Fourier or molecular replacement techniques, the crystal structures of HCV NS5B:ligand complexes where the ligand is a small-molecule inhibitor or substrate of this enzyme. This crystal form is suitable for structure-based drug design due to: (a) only modest concentrations of NaCl and PEG used for crystallization and (b) exposure of the active site to solvent channels. A schematic-representation of the HCV NS5B RdRp structure is shown in FIG. 1(b).

[0083] FIG. 1(b) contains schematic representations of the HCV NS5B RdRp monomer in a single large image, showing the location of the structural motifs in the three dimensional structure. The conserved structural motifs found in polymerases [Hansen et al., Structure, 5:1109-1122 (1997)] are denoted as lettered dark gray regions; the remainder of the molecule is lighter. The amino acid sequence of these motifs is shown (FIG. 1(a)), above FIG. 1(b) and are:

[0084] Motif A: This region forms one strand of the central beta-sheet and contributes an aspartate (D) to the active site;

[0085] Motif B: This region determines specificity between a NTP and dNTP substrate;

[0086] Motif C: This motif contains the sequence motif GDD and is directly implicated in divalent metal binding and nucleotidyl transferase activity;

[0087] Motif D: Buttresses the central beta-sheet; and

[0088] Motif E: Determines specificity between DNA and RNA template.

[0089] These motifs have all individually been shown to be required for catalytic activity [Hansen et al., Structure, 5:1109-1122 (1997); Joyce & Steitz, Ann. Rev. Biochem. 63:777-822 (1994); Poch et al., EMBO J. 8:3867-3874 (1989); Sousa, Trends Biochem Sci. 21:186-190 (1996)]. The three-dimensional colocalization of the motifs (in the `palm` subdomain) defines the position of the catalytic active site. Additionally, the `thumb` and `fingers` regions (denoted on the Figure), have been shown to bind to the primer strand substrate and template strand substrate, respectively, in other members of the greater polymerase family [Doublie et al., Nature 391:251-258 (1998); Huang et al., Science 282:1669-1675 (1998); Jacobo-Molina et al., Proc. Natl. Acad. Sci. USA 90:6320-632 (1993); Kiefer et al., Nature 391:304-307 (1998), Pelletier et al., Science 264:1891-1903 (1994)].

[0090] FIG. 1(b) was created using Molscript and Raster3D [Kraulis, J. Appl. Crystallogr. 24:946-950 (1991); Merritt & Bacon, Meth. Enzymol. 276:505-524 (1997)].

[0091] Table 1 lists the atomic structure coordinates for hepatitis C virus recombinant tNS5B polymerase, as derived by x-ray diffraction from crystals. The specific columns in Table 1 are defined as follows:

1 Column Description 1 Residue number (using numbering scheme of Table 1) 2 Residue name, using one-letter code (X = solvent) 3 Atom name, conventional PDB nomenclature (OW = solvent) 4 X-coordinate in orthogonal .ANG.ngstroms, multiplied by 10 5 Y-coordinate in orthogonal .ANG.ngstroms, multiplied by 10 6 Z-coordinate in orthogonal .ANG.ngstroms, multiplied by 10 7 B-factor, in .ANG..sup.2

[0092] The descriptions of the foregoing embodiments of the invention have been presented for purpose of illustration and description. They are not intended to be exhaustive or to limit the invention to the precise forms disclosed, and obviously many modifications and variations are possible in light of the above teaching. The embodiments were chosen and described in order to best explain the principles of the invention to thereby enable others skilled in the art to utilize the invention in various embodiments and with various modifications as are suited to the particular use contemplated. It is intended that the scope of the invention be defined by the claims appended hereto.

2 TABLE I 7 H N 161 376 196 40 7 H CA 152 378 208 40 7 H C 159 374 222 36 7 H O 152 369 231 32 7 H CB 138 371 207 42 7 H CG 129 376 196 44 7 H ND1 124 368 187 43 7 H CD2 125 389 193 42 7 H CE1 117 375 178 46 7 H NE2 117 388 182 43 8 H N 172 376 223 33 8 H CA 178 373 235 31 8 H C 178 384 245 24 8 H O 178 395 241 19 8 H CB 193 369 232 38 8 H CG 195 356 225 45 8 H ND1 201 354 213 44 8 H CD2 190 343 229 45 8 H CE1 200 342 209 48 8 H NE2 194 335 219 50 9 S N 177 380 258 22 9 S CA 177 391 268 20 9 S C 189 399 268 18 9 S O 189 411 271 17 9 S CB 175 384 282 18 9 S OG 183 372 283 19 10 Y N 201 393 265 18 10 Y CA 214 400 265 21 10 Y C 223 394 255 20 10 Y O 222 383 251 20 10 Y CB 221 399 278 17 10 Y CG 214 405 291 17 10 Y CD1 216 419 294 16 10 Y CD2 206 397 299 19 10 Y CE1 209 424 305 19 10 Y CE2 200 403 310 19 10 Y CZ 201 416 313 17 10 Y OH 195 421 323 25 11 T N 233 403 250 22 11 T CA 243 398 241 25 11 T C 256 404 248 25 11 T O 256 415 253 26 11 T CB 243 404 226 25 11 T OG1 240 418 226 28 11 T CG2 232 396 218 26 12 W N 266 396 249 25 12 W CA 279 400 256 26 12 W C 291 401 247 27 12 W O 293 393 238 28 12 W CB 281 390 267 20 12 W CG 269 388 276 20 12 W CD1 261 378 277 19 12 W CD2 265 398 286 19 12 W NE1 252 380 287 19 12 W CE2 254 392 293 19 12 W CE3 269 410 291 17 12 W CZ2 247 398 303 16 12 W CZ3 262 416 301 21 12 W CH2 251 410 307 14 13 T N 299 411 250 28 13 T CA 312 413 242 28 13 T C 323 405 248 31 13 T O 332 400 241 35 13 T CB 317 428 242 26 13 T OG1 319 432 256 27 13 T CG2 307 437 235 26 14 G N 323 403 261 31 14 G CA 333 395 267 30 14 G C 341 404 277 30 14 G O 350 399 284 31 15 A N 339 417 277 27 15 A CA 345 426 286 26 15 A C 339 422 300 29 15 A O 327 419 301 29 15 A CB 343 441 283 22 16 L N 347 423 310 31 16 L CA 342 419 324 30 16 L C 334 429 331 24 16 L O 336 441 329 25 16 L CB 354 415 332 30 16 L CG 363 404 328 33 16 L CD1 375 403 337 35 16 L CD2 356 391 328 32 17 I N 325 425 339 26 17 I CA 316 433 347 25 17 I C 326 436 359 25 17 I O 330 426 366 26 17 I CB 303 427 353 21 17 I CG1 294 423 341 19 17 I CG2 296 436 362 18 17 I CD1 281 418 344 21 18 T N 331 448 360 25 18 T CA 341 451 370 27 18 T C 336 459 382 28 18 T O 326 466 382 26 18 T CB 352 459 363 22 18 T OG1 347 471 357 23 18 T CG2 359 451 353 20 19 P N 343 457 393 30 19 P CA 339 463 406 33 19 P C 344 478 406 38 19 P O 352 482 398 37 19 P CB 346 455 417 32 19 P CG 358 450 410 33 19 P CD 354 447 396 30 20 C N 339 485 416 43 20 C CA 343 499 418 46 20 C C 355 498 428 48 20 C O 366 497 424 52 20 C CB 332 508 423 48 20 C SG 334 525 417 65 21 A N 351 498 441 47 21 A CA 361 497 451 45 21 A C 364 482 454 44 21 A O 359 474 447 46 21 A CB 357 504 464 46 22 A N 372 479 464 44 22 A CA 375 466 468 42 22 A C 362 460 473 40 22 A O 353 467 479 38 22 A CB 386 465 479 44 23 E N 361 446 472 37 23 E CA 349 439 476 35 23 E C 353 428 486 33 23 E O 362 421 484 35 23 E CB 342 433 464 32 23 E CG 337 442 453 30 23 E CD 332 435 441 33 23 E OE1 339 427 435 33 23 E OE2 320 437 437 33 24 E N 345 427 497 32 24 E CA 346 417 507 29 24 E C 336 406 505 27 24 E O 324 410 502 28 24 E CB 344 423 521 30 24 E CG 354 434 525 39 24 E CD 351 437 540 41 24 E OE1 342 445 542 40 24 E OE2 359 432 548 43 25 S N 339 394 506 28 25 S CA 329 383 505 28 25 S C 327 377 519 26 25 S O 316 372 522 26 25 S CB 334 373 495 30 25 S OG 345 365 500 34 26 K N 338 377 527 26 26 K CA 337 370 540 28 26 K C 332 380 551 20 26 K O 336 392 551 20 26 K CB 351 365 544 29 26 K CG 363 375 544 41 26 K CD 367 378 529 43 26 K CE 372 392 528 40 26 K NZ 370 396 514 41 27 L N 324 375 560 23 27 L CA 318 383 571 22 27 L C 329 390 579 21 27 L O 337 384 585 23 27 L CB 310 374 580 23 27 L CG 302 380 592 16 27 L CD1 293 391 588 14 27 L CD2 295 369 599 16 28 P N 329 404 579 22 28 P CA 338 411 587 23 28 P C 335 408 601 23 28 P O 324 407 605 22 28 P CB 335 426 583 23 28 P CG 327 425 571 25 28 P CD 319 412 572 22 29 I N 346 407 609 20 29 I CA 344 403 623 19 29 I C 350 414 633 23 29 I O 362 417 632 24 29 I CB 350 390 627 17 29 I CG1 342 379 619 20 29 I CG2 349 387 641 20 29 I CD1 328 377 622 12 30 N N 342 419 642 22 30 N CA 347 429 652 20 30 N C 344 423 666 16 30 N O 342 411 667 18 30 N CB 341 443 650 18 30 N CG 327 445 653 17 30 N OD1 320 435 657 20 30 N ND2 322 457 652 18 31 A N 345 431 676 19 31 A CA 342 426 690 20 31 A C 328 423 693 22 31 A O 325 415 702 23 31 A CB 348 436 700 19 32 L N 318 429 686 23 32 L CA 304 427 688 23 32 L C 298 415 681 23 32 L O 288 410 685 26 32 L CB 296 440 683 20 32 L CG 301 453 689 23 32 L CD1 294 465 683 21 32 L CD2 298 453 704 29 33 S N 305 411 670 23 33 S CA 301 399 662 22 33 S C 295 387 669 24 33 S O 284 383 667 24 33 S CB 312 395 653 18 33 S OG 316 406 645 17 34 N N 303 381 678 26 34 N CA 299 369 685 25 34 N C 287 369 695 23 34 N O 281 359 698 22 34 N CB 312 362 692 29 34 N CG 322 357 682 35 34 N OD1 318 351 672 37 34 N ND2 334 358 685 40 35 S N 284 381 700 22 35 S CA 272 382 708 25 35 S C 259 380 700 27 35 S O 249 377 705 28 35 S CB 271 396 715 23 35 S OG 270 407 706 30 36 L N 261 382 686 26 36 L CA 249 379 677 24 36 L C 250 366 669 24 36 L O 241 358 669 26 36 L CB 248 391 668 22 36 L CG 237 390 656 20 36 L CD1 223 389 662 22 36 L CD2 238 401 647 19 37 L N 262 364 663 23 37 L CA 263 352 654 25 37 L C 277 345 655 25 37 L O 287 351 654 27 37 L CB 261 356 640 21 37 L CG 258 346 629 21 37 L CD1 247 352 619 18 37 L CD2 270 344 621 22 38 R N 277 332 658 27 38 R CA 289 324 659 31 38 R C 294 317 647 30 38 R O 306 315 644 27 38 R CB 289 315 671 38 38 R CG 289 322 684 47 38 R CD 286 313 696 57 38 R NE 294 316 708 68 38 R CZ 296 307 717 73 38 R NH1 291 295 717 75 38 R NH2 304 311 728 75 39 H N 284 312 639 29 39 H CA 288 304 627 30 39 H C 291 314 615 29 39 H O 284 313 605 32 39 H CB 276 295 623 28 39 H CG 273 284 633 28 39 H ND1 263 275 632 32 39 H CD2 280 282 645 32 39 H CE1 263 267 642 33 39 H NE2 273 271 650 33 40 H N 302 321 616 26 40 H CA 306 331 606 29 40 H C 307 326 591 29 40 H O 305 334 582 27 40 H CB 320 337 610 28 40 H CG 320 342 624 33 40 H ND1 332 344 632 31 40 H CD2 310 346 633 33 40 H CE1 329 348 644 32 40 H NE2 316 349 645 32 41 N N 311 313 589 29 41 N CA 312 308 576 33 41 N C 299 305 569 34 41 N O 299 301 557 37 41 N CB 320 295 577 38 41 N CG 335 297 581 45 41 N OD1 340 308 581 47 41 N ND2 342 286 584 48 42 M N 288 308 575 35 42 M CA 275 307 569 33 42 M C 271 320 561 33 42 M O 263 319 552 33 42 M CB 265 304 579 38 42 M CG 267 292 588 41 42 M SD 262 275 579 57 42 M CE 242 278 576 48 43 V N 278 331 565 28 43 V CA 275 344 560 26 43 V C 285 349 549 26 43 V O 297 348 551 28 43 V CB 274 354 571 20 43 V CG1 271 368 565 16 43 V CG2 262 351 580 20 44 Y N 280 354 538 25 44 Y CA 288 359 527 24 44 Y C 281 370 520 23 44 Y O 269 372 520 21 44 Y CB 292 347 518 22 44 Y CG 280 343 509 25 44 Y CD1 271 334 514 26 44 Y CD2 278 /348 496 25 44 Y CE1 260 330 507 24 44 Y CE2 267 344 489 22 44 Y CZ 258 335 494 25 44 Y OH 246 331 487 27 45 A N 289 378 513 21 45 A CA 284 389 504 23 45 A C 287 384 490 27 45 A O 297 377 487 30 45 A CB 290 402 507 16 46 T N 277 387 481 24 46 T CA 280 383 467 21 46 T C 289 394 462 22 46 T O 289 405 466 24 46 T CB 267 384 458 15 46 T OG1 261 397 460 17 46 T CG2 258 373 462 17 47 T N 297 390 452 26 47 T CA 307 400 446 26 47 T C 308 398 431 25 47 T O 303 388 425 23 47 T CB 321 396 453 25 47 T OG1 330 407 452 33 47 T CG2 327 384 446 22 48 S N 314 408 424 26 48 S CA 315 407 409 26 48 S C 322 395 404 29 48 S O 320 391 393 31 48 S CB 322 420 404 24 48 S OG 336 419 407 26 49 R N 329 388 413 29 49 R CA 336 376 410 27 49 R C 327 365 405 28 49 R O 332 355 399 28 49 R CB 345 371 421 32 49 R CG 357 380 425 35 49 R CD 367 374 434 42 49 R NE 363 374 448 52 49 R CZ 364 385 456 54 49 R NH1 369 396 451 55 49 R NH2 361 384 469 55 50 S N 314 366 407 26 50 S CA 304 356 402 26 50 S C 295 362 392 24 50 S O 285 356 388 22 50 S CB 296 350 414 26 50 S OG 287 360 419 29 51 A N 298 374 386 25 51 A CA 290 381 376 26 51 A C 288 372 364 28 51 A O 277 372 357 27 51 A CB 296 394 373 18 52 G N 299 364 360 30 52 G CA 299 355 349 27 52 G C 287 345 350 29 52 G O 280 343 340 29 53 L N 286 339 362 29 53 L CA 276 329 364 30 53 L C 262 335 363 29 53 L O 253 329 358 30 53 L CB 278 324 378 32 53 L CG 287 312 380 34 53 L CD1 290 310 394 34 53 L CD2 281 300 373 35 54 R N 260 348 368 27 54 R CA 248 355 367 27 54 R C 244 357 352 26 54 R O 233 354 348 23 54 R CB 248 368 375 26 54 R CG 235 376 374 26 54 R CD 223 369 379 28 54 R NE 223 364 393 34 54 R CZ 214 357 398 35 54 R NH1 204 353 391 35 54 R NH2 215 353 411 31 55 Q N 254 362 345 28 55 Q CA 253 365 331 29 55 Q C 247 353 324 29 55 Q O 238 354 315 29 55 Q CB 266 369 324 24 55 Q CG 271 383 326 25 55 Q CD 285 386 321 30 55 Q OE1 287 394 312 30 55 Q NE2 294 379 327 35 56 K N 251 341 327 29 56 K CA 247 329 321 31 56 K C 232 325 325 34 56 K O 225 320 316 37 56 K CB 256 317 325 32 56 K CG 270 319 320 37 56 K CD 279 307 324 41 56 K CE 293 309 317 45 56 K NZ 291 309 302 44 57 K N 228 328 337 35 57 K CA 214 325 341 33 57 K C 204 335 334 28 57 K O 194 331 329 33 57 K CB 212 326 356 34 57 K CG 221 316 364 44 57 K CD 217 316 379 49 57 K CE 227 307 387 49 57 K NZ 228 294 381 54 58 V N 207 348 334 26 58 V CA 199 358 328 24 58 V C 199 359 313 23 58 V O 190 366 307 22 58 V CB 202 372 334 23 58 V CG1 202 372 349 23 58 V CG2 216 377 330 22 59 T N 207 352 306 25 59 T CA 208 353 291 24 59 T C 201 341 284 24 59 T O 206 330 285 24 59 T CB 223 353 286 23 59 T OG1 229 364 293 23 59 T CG2 223 356 271 22 60 F N 190 344 278 24 60 F CA 182 334 271 25 60 F C 173 341 260 23 60 F O 172 353 260 23 60 F CB 174 325 280 28 60 F CG 165 333 291 32 60 F CD1 152 337 287 31 60 F CD2 170 335 303 31 60 F CE1 144 344 297 28 60 F CE2 162 342 313 34 60 F CZ 149 346 310 35 61 D N 168 332 251 26 61 D CA 159 337 240 29 61 D C 145 336 245 27 61 D O 141 326 251 29 61 D CB 162 328 228 34 61 D CG 154 332 216 41 61 D OD1 155 344 211 44 61 D OD2 146 324 210 45 62 R N 137 346 242 26 62 R CA 123 345 246 25 62 R C 113 346 235 25 62 R O 115 352 224 23 62 R CB 119 355 258 23 62 R CG 125 368 257 26 62 R CD 139 369 260 21 62 R NE 142 381 268 25 62 R CZ 141 393 263 23 62 R NH1 139 395 250 31 62 R NH2 141 404 271 29 63 L N 102 338 237 27 63 L CA 91 338 227 26 63 L C 78 341 234 23 63 L O 76 337 246 25 63 L CB 90 324 221 28 63 L CG 103 319 214 30 63 L CD1 101 304 211 33 63 L CD2 105 327 201 31 64 Q N 69 348 228 24 64 Q CA 56 351 233 20 64 Q C 45 348 223 21 64 Q O 45 352 212 18 64 Q CB 55 366 237 19 64 Q CG 61 369 250 22 64 Q CD 58 383 253 23 64 Q OE1 60 393 245 25 64 Q NE2 53 386 266 24 65 V N 34 341 228 22 65 V CA 23 338 220 23 65 V C 11 345 228 22 65 V O 7 341 239 23 65 V CB 21 322 220 23 65 V CG1 8 319 214 24 65 V CG2 33 316 212 23 66 L N 7 356 222 19 66 L CA -3 364 227 20 66 L C -17 361 223 20 66 L O -20 362 211 21 66 L CB 0 379 225 18 66 L CG 11 385 234 17 66 L CD1 20 375 240 18 66 L CD2 18 396 228 10 67 D N -25 357 232 19 67 D CA -39 353 228 20 67 D C -50 364 232 17 67 D O -47 375 236 15 67 D CB -43 339 234 20 67 D CG -44 339 249 20 67 D OD1 -41 349 256 18 67 D OD2 -47 328 255 28 68 D N -63 359 230 19 68 D CA -74 368 233 20 68 D C -76 372 247 17 68 D O -79 384 250 17 68 D CB -87 362 228 23 68 D CG -88 364 213 22 68 D OD1 -91 375 208 27 68 D OD2 -86 354 205 21 69 H N -73 363 257 17 69 H CA -74 366 271 19 69 H C -63 377 274 20 69 H O -66 387 282 20 69 H CB -71 354 280 20 69 H CG -83 344 280 21 69 H ND1 -81 331 279 20 69 H CD2 -96 347 282 19 69 H CE1 -93 325 280 21 69 H NE2 -102 334 282 22 70 Y N -52 377 268 19 70 Y CA -41 387 270 16 70 Y C -46 400 265 17 70 Y O -45 410 273 19 70 Y CB -28 382 263 18 70 Y CG -17 392 263 19 70 Y CD1 -16 403 254 20 70 Y CD2 -7 392 273 18 70 Y CE1 -5 412 255 19 70 Y CE2 3 401 274 17 70 Y CZ 3 411 265 17 70 Y OH 13 421 266 19 71 R N -51 401 253 18 71 R CA -57 414 248 19 71 R C -69 419 255 16 71 R O -71 431 256 16 71 R CB -59 414 232 22 71 R CG -47 413 224 21 71 R CD -50 412 209 18 71 R NE -58 400 206 17 71 R CZ -52 388 204 18 71 R NH1 -39 386 204 20 71 R NH2 -60 377 202 19 72 D N -78 410 260 18 72 D CA -90 414 267 18 72 D C -86 421 280 20 72 D O -92 431 284 18 72 D CB -98 401 271 19 72 D CG -106 396 259 21 72 D OD1 -108 403 249 23 72 D OD2 -111 384 260 24 73 V N -77 415 288 18 73 V CA -73 420 301 17 73 V C -66 434 298 17 73 V O -69 444 305 14 73 V CB -63 411 308 17 73 V CG1 -57 417 320 15 73 V CG2 -70 398 313 15 74 L N -57 435 288 14 74 L CA -50 447 285 14 74 L C -60 458 282 15 74 L O -58 470 286 15 74 L CB -40 446 273 16 74 L CG -33 458 268 16 74 L CD1 -25 465 279 13 74 L CD2 -23 454 257 17 75 K N -71 455 274 17 75 K CA -81 465 271 18 75 K C -88 471 283 13 75 K O -90 482 284 17 75 K CB -91 460 261 19 75 K CG -99 472 255 20 75 K CD -110 467 245 22 75 K CE -116 479 238 27 75 K NZ -126 475 229 30 76 E N -90 462 293 16 76 E CA -96 466 305 20 76 E C -87 475 313 17 76 E O -91 485 319 19 76 E CB -100 454 314 22 76 E CG -110 445 307 30 76 E CD -112 432 314 32 76 E OE1 -108 431 326 35 76 E OE2 -116 422 307 35 77 M N -74 472 313 16 77 M CA -64 480 321 16 77 M C -63 494 315 16 77 M O -63 503 323 15 77 M CB -51 473 321 17 77 M CG -50 461 330 18 77 M SD -34 449 327 20 77 M CE -19 461 335 20 78 K N -62 495 302 17 78 K CA -61 508 296 16 78 K C -74 516 298 18 78 K O -72 529 300 17 78 K CB -59 506 281 17 78 K CG -46 500 277 16 78 K CD -43 503 262 23 78 K CE -33 494 256 30 78 K NZ -32 497 242 33 79 A N -86 510 299 20 79 A CA -98 518 302 19 79 A C -97 525 316 17 79 A O -101 537 317 16 79 A CB -110 509 301 14 80 K N -91 518 325 18 80 K CA -88 523 339 18 80 K C -77 534 338 18 80 K O -78 545 344 18 80 K CB -85 512 348 19 80 K CG -97 504 352 23 80 K CD -92 492 360 30 80 K CE -104 484 365 35 80 K NZ -115 493 371 41 81 A N -66 531 331 18 81 A CA -55

540 330 19 81 A C -59 554 324 21 81 A O -54 564 326 18 81 A CB -43 534 321 18 82 S N -70 553 316 22 82 S CA -75 565 309 22 82 S C -81 575 319 21 82 S O -83 587 316 21 82 S CB -85 562 298 24 82 S OG -79 555 288 35 83 T N -85 571 331 22 83 T CA -90 580 341 20 83 T C -79 587 349 19 83 T O -82 597 356 21 83 T CB -100 573 351 23 83 T OG1 -92 563 359 22 83 T CG2 -110 565 343 22 84 V N -67 583 348 18 84 V CA -56 589 355 17 84 V C -51 602 348 17 84 V O -51 603 336 21 84 V CB -43 579 355 16 84 V CG1 -31 586 361 12 84 V CG2 -47 566 362 13 85 K N -48 612 357 17 85 K CA -43 625 352 19 85 K C -30 626 360 22 85 K O -30 626 372 20 85 K CB -52 637 355 21 85 K CG -47 650 350 21 85 K CD -57 661 350 26 85 K CE -50 674 344 31 85 K NZ -60 685 343 39 86 A N -19 627 352 21 86 A CA -6 629 359 19 86 A C 0 642 356 22 86 A O -1 647 345 24 86 A CB 2 617 355 21 87 K N 8 647 365 21 87 K CA 14 660 364 24 87 K C 29 658 361 22 87 K O 35 648 365 21 87 K CB 13 668 376 30 87 K CG 0 668 383 42 87 K CD -12 675 375 48 87 K CE -12 690 376 53 87 K NZ -2 697 367 56 88 L N 36 668 355 20 88 L CA 50 668 352 23 88 L C 56 674 365 24 88 L O 51 684 370 26 88 L CB 52 677 340 24 88 L CG 64 675 330 24 88 L CD1 66 661 325 20 88 L CD2 60 684 318 26 89 L N 67 668 370 22 89 L CA 74 674 381 23 89 L C 84 685 376 23 89 L O 90 684 366 27 89 L CB 82 663 389 23 89 L CG 78 657 402 23 89 L CD1 63 653 401 18 89 L CD2 87 646 405 20 90 S N 86 696 384 23 90 S CA 95 706 380 23 90 S C 110 701 383 23 90 S O 111 690 388 21 90 S CB 93 719 389 23 90 S OG 95 716 403 26 91 V N 120 708 379 25 91 V CA 134 704 381 26 91 V C 137 703 396 26 91 V O 142 693 401 25 91 V CB 144 712 374 23 91 V CG1 158 707 376 23 91 V CG2 141 713 359 28 92 E N 133 713 403 28 92 E CA 135 714 418 31 92 E C 128 702 425 28 92 E O 134 696 434 27 92 E CB 131 727 424 34 92 E CG 118 734 418 47 92 E CD 121 744 407 52 92 E OE1 127 741 396 52 92 E OE2 116 756 409 53 93 E N 116 699 421 27 93 E CA 109 687 427 23 93 E C 116 674 425 21 93 E O 117 666 434 21 93 E CB 94 687 423 25 93 E CG 86 699 427 32 93 E CD 72 698 423 37 93 E OE1 69 695 411 39 93 E OE2 63 700 431 40 94 A N 120 671 412 21 94 A CA 127 659 409 19 94 A C 140 658 416 17 94 A O 145 648 420 20 94 A CB 128 657 394 20 95 C N 147 670 417 18 95 C CA 160 670 424 20 95 C C 159 666 439 20 95 C O 168 659 444 21 95 C CB 166 684 423 15 95 C SG 172 689 406 25 96 K N 149 671 445 23 96 K CA 146 668 460 24 96 K C 143 654 462 25 96 K O 143 650 474 27 96 K CB 135 677 465 26 96 K CG 137 692 465 34 96 K CD 126 700 471 45 96 K CE 114 700 462 49 96 K NZ 106 713 464 46 97 L N 140 646 452 22 97 L CA 137 632 453 19 97 L C 150 623 452 16 97 L O 149 611 453 17 97 L CB 127 628 443 20 97 L CG 112 632 445 20 97 L CD1 105 629 432 17 97 L CD2 106 624 456 16 98 T N 161 629 449 22 98 T CA 174 622 447 21 98 T C 181 619 460 19 98 T O 183 628 468 20 98 T CB 183 632 437 23 98 T OG1 176 634 425 20 98 T CG2 197 626 435 18 99 P N 185 606 462 19 99 P CA 192 602 474 19 99 P C 205 610 475 25 99 P O 212 612 466 25 99 P CB 195 587 472 17 99 P CG 183 583 464 18 99 P CD 182 594 454 17 100 P N 208 614 488 27 100 P CA 221 622 490 29 100 P C 233 615 485 28 100 P O 243 621 481 32 100 P CB 221 624 505 28 100 P CG 207 625 508 28 100 P CD 201 613 500 28 101 H N 233 601 485 30 101 H CA 244 593 480 31 101 H C 242 586 467 30 101 H O 248 575 465 30 101 H CB 249 584 492 38 101 H CG 256 591 503 46 101 H ND1 251 593 516 46 101 H CD2 268 598 503 49 101 H CE1 259 600 523 50 101 H NE2 270 603 516 51 102 S N 234 591 459 28 102 S CA 231 585 446 25 102 S C 244 586 437 25 102 S O 251 596 439 25 102 S CB 219 593 439 23 102 S OG 215 587 427 22 103 A N 247 576 429 23 103 A CA 259 576 421 21 103 A C 260 590 413 24 103 A O 250 594 406 22 103 A CB 258 565 411 19 104 K N 272 596 414 23 104 K CA 274 609 407 24 104 K C 274 608 392 21 104 K O 276 597 386 20 104 K CB 288 615 411 25 104 K CG 300 606 407 30 104 K CD 313 614 408 37 104 K CE 325 605 404 39 104 K NZ 338 612 405 43 105 S N 272 619 385 22 105 S CA 271 620 371 25 105 S C 285 619 364 28 105 S O 295 623 370 28 105 S CB 264 633 367 24 105 S OG 264 635 353 23 106 K N 286 614 352 27 106 K CA 298 613 345 27 106 K C 302 627 340 27 106 K O 313 629 335 30 106 K CB 297 603 333 29 106 K CG 294 589 336 40 106 K CD 294 580 323 44 106 K CE 290 566 326 48 106 K NZ 293 557 315 50 107 F N 292 636 341 28 107 F CA 294 650 336 24 107 F C 298 661 346 26 107 F O 294 672 344 27 107 F CB 282 653 327 25 107 F CG 278 643 317 23 107 F CD1 286 643 305 24 107 F CD2 269 633 319 21 107 F CE1 283 632 296 23 107 F CE2 267 623 310 19 107 F CZ 274 623 299 24 108 G N 305 657 356 28 108 G CA 310 667 366 27 108 G C 301 673 377 26 108 G O 303 685 380 24 109 Y N 293 665 383 28 109 Y CA 284 669 394 23 109 Y C 278 657 400 21 109 Y O 278 646 393 22 109 Y CB 273 679 389 26 109 Y CG 262 673 380 27 109 Y CD1 251 666 386 28 109 Y CD2 263 674 366 25 109 Y CE1 241 661 378 27 109 Y CE2 254 668 358 25 109 Y CZ 243 662 364 27 109 Y OH 233 656 356 25 110 G N 274 658 412 22 110 G CA 268 646 419 23 110 G C 255 649 426 22 110 G O 250 660 424 23 111 A N 250 639 433 22 111 A CA 237 640 441 22 111 A C 236 652 450 28 111 A O 226 658 451 29 111 A CB 235 627 448 19 112 K N 247 656 456 34 112 K CA 247 667 465 35 112 K C 245 680 457 34 112 K O 239 690 462 32 112 K CB 259 668 474 41 112 K CG 261 656 484 49 112 K CD 248 655 493 52 112 K CE 249 643 502 57 112 K NZ 262 642 511 59 113 D N 251 680 445 32 113 D CA 250 692 436 29 113 D C 236 692 431 26 113 D O 230 703 429 26 113 D CB 260 690 425 31 113 D CG 274 690 429 33 113 D OD1 278 699 437 36 113 D OD2 282 681 425 31 114 V N 230 681 428 26 114 V CA 216 679 423 24 114 V C 206 684 434 24 114 V O 199 694 431 22 114 V CB 213 664 419 22 114 V CG1 198 663 417 19 114 V CG2 221 660 407 18 115 R N 207 678 446 22 115 R CA 198 682 457 25 115 R C 200 697 461 27 115 R O 190 704 465 27 115 R CB 200 674 469 25 115 R CG 198 659 467 22 115 R CD 200 651 480 25 115 R NE 193 658 491 25 115 R CZ 179 657 493 25 115 R NH1 172 649 485 29 115 R NH2 173 665 502 26 116 N N 212 703 459 29 116 N CA 215 717 462 31 116 N C 211 726 450 31 116 N O 212 739 452 28 116 N CB 230 718 464 36 116 N CG 234 716 479 43 116 N OD1 229 724 487 47 116 N ND2 243 707 482 44 117 L N 207 721 439 30 117 L CA 202 728 427 29 117 L C 213 737 421 29 117 L O 211 748 416 30 117 L CB 190 737 431 26 117 L CG 178 730 438 22 117 L CD1 167 740 441 24 117 L CD2 173 718 430 20 118 S N 226 732 421 29 118 S CA 237 740 416 31 118 S C 235 742 401 32 118 S O 230 733 394 32 118 S CB 250 733 418 33 118 S OG 252 722 409 36 119 S N 239 754 396 33 119 S CA 238 757 382 33 119 S C 243 747 372 30 119 S O 238 744 362 29 119 S CB 243 771 379 36 119 S OG 257 773 384 40 120 K N 255 741 375 31 120 K CA 261 731 367 31 120 K C 252 719 365 31 120 K O 249 715 354 27 120 K CB 275 727 373 33 120 K CG 282 717 364 37 120 K CD 296 715 369 41 120 K CE 304 706 360 46 120 K NZ 318 704 365 49 121 A N 246 714 376 28 121 A CA 237 702 376 25 121 A C 224 706 369 26 121 A O 219 698 360 27 121 A CB 234 697 390 21 122 V N 218 717 373 25 122 V CA 205 721 367 27 122 V C 206 724 352 27 122 V O 197 721 344 27 122 V CB 199 734 375 27 122 V CG1 189 741 367 28 122 V CG2 193 729 388 26 123 N N 217 730 348 28 123 N CA 219 733 334 28 123 N C 221 720 326 25 123 N O 214 719 316 25 123 N CB 232 742 332 30 123 N CG 230 756 338 38 123 N OD1 219 761 339 40 123 N ND2 241 763 341 42 124 H N 228 711 331 25 124 H CA 229 698 325 25 124 H C 216 690 324 27 124 H O 214 682 314 24 124 H CB 240 690 331 21 124 H CG 242 676 325 24 124 H ND1 239 664 331 23 124 H CD2 246 672 313 23 124 H CE1 241 654 323 23 124 H NE2 246 659 312 26 125 I N 209 690 335 26 125 I CA 196 683 335 22 125 I C 187 689 324 21 125 I O 181 681 317 20 125 I CB 189 685 350 24 125 I CG1 196 675 360 20 125 I CG2 174 682 349 20 125 I CD1 195 680 374 23 126 H N 187 702 323 22 126 H CA 179 709 313 26 126 H C 184 704 298 29 126 H O 175 703 289 28 126 H CB 180 724 314 28 126 H CG 170 730 324 36 126 H ND1 173 741 331 39 126 H CD2 158 726 327 39 126 H CE1 163 744 339 40 126 H NE2 153 734 337 40 127 S N 197 702 297 27 127 S CA 201 697 284 25 127 S C 197 683 281 23 127 S O 194 680 269 25 127 S CB 217 700 282 27 127 S OG 225 692 290 28 128 V N 197 675 291 20 128 V CA 192 661 289 18 128 V C 178 660 286 20 128 V O 174 652 277 19 128 V CB 194 652 302 16 128 V CG1 191 638 300 9 128 V CG2 209 654 307 19 129 W N 169 668 293 21 129 W CA 155 669 290 21 129 W C 152 673 276 21 129 W O 145 667 268 19 129 W CB 149 679 300 17 129 W CG 133 679 299 22 129 W CD1 126 689 294 20 129 W CD2 124 669 304 21 129 W NE1 112 686 295 19 129 W CE2 111 674 301 18 129 W CE3 126 657 310 17 129 W CZ2 100 667 305 20 129 W CZ3 114 649 314 17 129 W CH2 102 654 311 17 130 K N 159 684 272 23 130 K CA 158 690 258 24 130 K C 161 679 248 24 130 K O 154 677 238 23 130 K CB 167 702 256 27 130 K CG 166 709 243 34 130 K CD 175 721 242 40 130 K CE 170 733 251 49 130 K NZ 180 745 252 52 131 D N 172 672 251 23 131 D CA 177 661 242 22 131 D C 166 650 241 22 131 D O 165 644 231 20 131 D CB 190 656 246 23 131 D CG 196 645 237 21 131 D OD1 199 648 225 25 131 D OD2 196 633 240 21 132 L N 159 647 252 20 132 L CA 149 637 252 19 132 L C 137 641 243 19 132 L O 131 632 237 21 132 L CB 144 634 266 18 132 L CG 152 625 276 19 132 L CD1 144 625 289 16 132 L CD2 154 612 270 18 133 L N 134 653 243 20 133 L CA 123 658 234 20 133 L C 126 658 220 25 133 L O 118 656 211 26 133 L CB 118 672 239 16 133 L CG 113 674 253 17 133 L CD1 108 688 254 18 133 L CD2 102 664 257 13 134 E N 139 661 217 25 134 E CA 143 662 203 25 134 E C 149 650 196 25 134 E O 148 649 184 28 134 E CB 153 674 201 29 134 E CG 146 687 205 39 134 E CD 154 699 205 44 134 E OE1 167 698 208 48 134 E OE2 149 710 203 47 135 D N 152 639 204 26 135 D CA 157 627 199 22 135 D C 149 615 205 23 135 D O 149 614 217 23 135 D CB 172 626 203 24 135 D CG 180 614 197 23 135 D OD1 173 603 194 21 135 D OD2 192 615 195 26 136 T N 143 607 197 21 136 T CA 134 596 201 20 136 T C 141 583 197 17 136 T O 135 572 198 17 136 T CB 120 598 196 22 136 T OG1 112 606 205 26 136 T CG2 112 585 193 26 137 V N 153 583 192 19 137 V CA 159 571 187 19 137 V C 172 566 193 17 137 V O 173 554 195 20 137 V CB 160 571 171 20 137 V CG1 147 574 164 22 137 V CG2 170 581 167 21 138 T N 181 575 196 18 138 T CA 194 571 201 19 138 T C 195 563 214 20 138 T O 191 569 225 21 138 T CB 204 583 202 18 138 T OG1 201 592 191 17 138 T CG2 219 578 201 17 139 P N 200 551 215 22 139 P CA 201 543 227 22 139 P C 209 551 238 21 139 P O 219 557 234 22 139 P CB 208 530 223 22 139 P CG 203 528 209 23 139 P CD 204 543 203 21 140 I N 204 552 250 21 140 I CA 211 559 261 20 140 I C 221 549 268 17 140 I O 218 537 269 19 140 I CB 200 565 270 19 140 I CG1 193 577 263 18 140 I CG2 206 569 284 18 140 I CD1 181 582 270 21 141 D N 232 555 272 19 141 D CA 242 547 279 19 141 D C 237 542 293 20 141 D O 230 549 300 21 141 D CB 255 555 281 22 141 D CG 267 547 286 27 141 D OD1 268 535 282 23 141 D OD2 275 552 294 36 142 T N 242 531 296 19 142 T CA 239 524 309 22 142 T C 251 518 315 25 142 T O 261 514 308 25 142 T CB 228 513 305 23 142 T OG1 215 518 309 30 142 T CG2 232 500 311 22 143 T N 251 518 329 24 143 T CA 263 511 336 22 143 T C 258 498 342 20 143 T O 247 497 347 22 143 T CB 267 520 348 20 143 T OG1 272 533 343 19 143 T CG2 278 513 356 20 144 I N 266 488 341 15 144 I CA 263 475 346 18 144 I C 272 472 358 23 144 I O 284 473 357 21 144 I CB 263 463 335 18 144 I CG1 257 451 341 16 144 I CG2 277 461 330 21 144 I CD1 254 440 331 15 145 M N 266 468 369 22 145 M CA 274 465 381 24 145 M C 269 452 388 22 145 M O 257 448 385 20 145 M CB 271 476 392 26 145 M CG 276 490 389 33 145 M SD 297 491 389 45 145 M CE 299 510 397 45 146 A N 278 446 395 21 146 A CA 274 434 402 22 146 A C 271 439 416 25 146 A O 278 448 422 24 146 A CB 286 424 403 22 147 K N 259 435 422 27 147 K CA 255 440 435 27 147 K C 262 431 446 21 147 K O 263 419 444 21 147 K CB 240 439 437 30 147 K CG 232 448 428 34 147 K CD 217 445 431 43 147 K CE 208 452 420 45 147 K NZ 193 448 422 44 148 N N 266 438 457 25 148 N CA 272 431 468 26 148 N C 260 429 478 23 148 N O 257 439 485 26 148 N CB 282 439 475 29 148 N CG 293 443 466 30 148 N OD1 296 455 465 33 148 N ND2 300 434 459 28 149 E N 255 417 480 26 149 E CA 244 415 489 28 149 E C 247 403 498 26 149 E O 254 394 494 26 149 E CB 231 413 482 28 149 E CG 226 424 474 30 149 E CD 213 422 467 34 149 E OE1 212 412 459 32 149 E OE2 204 430 468 39 150 V N 243 404 511 24 150 V CA 246 394 521 21 150 V C 236 383 522 20 150 V O 224 386 522 23 150 V CB 249 400 535 20 150 V CG1 251 390 546 21 150 V CG2 260 411 535 16 151 F N 240 370 523 18 151 F CA 231 359 524 20 151 F C 237 349 533 24 151 F O 249 350 537 24 151 F CB 228 352 510 24 151 F CG 221 361 500 23 151 F CD1 208 363 500 24 151 F CD2 229 368 491 25 151 F CE1 202 371 490 25 151 F CE2 224 376 481 25 151 F CZ 210 378 481 23 152 C N 229 339 537 25 152 C CA 233 327 544 28 152 C C 235 316 534 31 152 C O 226 315 525 33 152 C CB 223 324 555 26 152 C SG 227 308 564 28 153 V N 245 308 535 33 153 V CA 248 297 526 39 153 V C 236 287 525 43 153 V O 229 284 535 45 153 V CB 261 290 529 40 153 V CG1 263 279 519 45 153 V CG2 272 300 529 39 154 Q N 234 282 513 49 154 Q CA 224 272 509 51 154 Q C 210 277 511 53 154 Q O 205 284 501 57 154 Q CB 225 259 518 54 154 Q CG 239 252 516 60 154 Q CD 241 241 526 63 154 Q OE1 241 243 538 63 154 Q NE2 241 228 521 66 160 R N 262 288 470 41 160 R CA 261 302 472 40 160 R C 255 309 459 40 160 R O 258 304 448 41 160 R CB 274 308 476 39 160 R CG 281 300 486 42 160 R CD 291 308 495 48 160 R NE 298 318 487 49 160 R CZ 309 325 491 51 160 R NH1 314 323 503 52 160 R NH2 314 334 483 55 161 K N 247 319 460 37 161 K CA 241 327 449 37 161 K C 251 336 442 34 161 K O 259 343 448 35 161 K

CB 230 336 454 36 161 K CG 217 329 460 39 161 K CD 208 340 465 41 161 K CE 194 334 468 44 161 K NZ 193 324 479 47 162 P N 249 337 428 33 162 P CA 258 346 421 29 162 P C 253 360 423 28 162 P O 241 362 426 27 162 P CB 256 342 406 29 162 P CG 250 328 407 29 162 P CD 241 329 419 31 163 A N 261 370 422 23 163 A CA 257 384 424 21 163 A C 245 387 415 25 163 A O 244 381 404 24 163 A CB 269 393 421 18 164 R N 236 397 419 24 164 R CA 226 401 410 26 164 R C 231 413 403 27 164 R O 240 420 408 27 164 R CB 213 405 418 30 164 R CG 205 393 423 38 164 R CD 191 397 426 44 164 R NE 191 408 436 52 164 R CZ 184 420 434 58 164 R NH1 176 422 424 65 164 R NH2 184 429 444 59 165 L N 226 416 391 26 165 L CA 231 427 383 27 165 L C 222 439 383 25 165 L O 210 438 383 29 165 L CB 234 422 369 30 165 L CG 247 415 365 30 165 L CD1 254 408 376 25 165 L CD2 244 405 353 29 166 I N 228 451 384 20 166 I CA 221 464 384 22 166 I C 225 471 371 23 166 I O 237 472 368 21 166 I CB 223 472 397 23 166 I CG1 216 486 396 25 166 I CG2 238 475 398 25 166 I CD1 201 485 401 25 167 V N 215 476 364 20 167 V CA 217 484 352 17 167 V C 211 497 354 16 167 V O 199 498 356 17 167 V CB 211 476 340 14 167 V CG1 211 485 327 15 167 V CG2 218 463 338 15 168 F N 218 508 353 12 168 F CA 213 521 355 16 168 F C 218 533 346 19 168 F O 230 532 342 21 168 F CB 214 526 370 15 168 F CG 229 526 375 16 168 F CD1 236 514 378 15 168 F CD2 236 538 376 16 168 F CE1 249 514 382 14 168 F CE2 249 538 380 15 168 F CZ 256 526 383 9 169 P N 210 543 343 19 169 P CA 214 554 334 19 169 P C 221 564 343 22 169 P O 221 564 355 25 169 P CB 201 559 329 16 169 P CG 192 556 340 17 169 P CD 195 542 344 18 170 D N 227 574 337 19 170 D CA 234 585 344 21 170 D C 225 593 352 24 170 D O 213 594 350 27 170 D CB 241 594 334 21 170 D CG 250 604 340 19 170 D OD1 261 599 345 22 170 D OD2 247 616 341 17 171 L N 230 600 362 22 171 L CA 223 609 371 23 171 L C 214 618 364 23 171 L O 202 619 368 21 171 L CB 233 616 381 19 171 L CG 228 626 391 23 171 L CD1 217 620 399 23 171 L CD2 240 631 399 21 172 G N 219 626 354 23 172 G CA 210 635 347 23 172 G C 198 629 341 20 172 G O 187 636 340 20 173 V N 199 617 336 19 173 V CA 188 609 330 19 173 V C 178 605 341 20 173 V O 166 605 339 16 173 V CB 194 597 323 17 173 V CG1 182 587 318 12 173 V CG2 202 601 310 14 174 R N 184 601 352 18 174 R CA 176 597 364 18 174 R C 167 608 369 18 174 R O 155 605 372 19 174 R CB 184 592 375 18 174 R CG 190 578 373 21 174 R CD 194 572 386 23 174 R NE 208 569 386 33 174 R CZ 217 577 392 29 174 R NH1 213 588 399 39 174 R NH2 230 575 391 36 175 V N 172 620 369 16 175 V CA 164 632 374 17 175 V C 153 634 363 21 175 V O 141 638 367 18 175 V CB 172 644 375 15 175 V CG1 164 656 379 15 175 V CG2 182 642 387 16 176 C N 156 632 351 20 176 C CA 146 634 340 20 176 C C 135 623 340 17 176 C O 123 627 337 16 176 C CB 153 634 326 16 176 C SG 162 649 322 18 177 E N 138 611 344 17 177 E CA 128 600 345 18 177 E C 118 605 356 19 177 E O 106 603 354 16 177 E CB 134 587 350 14 177 E CG 142 580 340 20 177 E CD 146 566 345 22 177 E OE1 138 557 345 20 177 E OE2 157 565 350 28 178 K N 123 611 367 20 178 K CA 114 616 378 20 178 K C 104 626 373 21 178 K O 92 625 375 22 178 K CB 123 622 389 18 178 K CG 131 612 397 20 178 K CD 140 619 407 20 178 K CE 147 610 417 16 178 K NZ 155 600 410 21 179 M N 109 637 367 21 179 M CA 101 647 361 25 179 M C 90 642 352 24 179 M O 78 646 353 23 179 M CB 109 657 353 27 179 M CG 118 665 362 33 179 M SD 131 677 351 38 179 M CE 147 664 351 35 180 A N 93 633 343 21 180 A CA 84 627 333 22 180 A C 74 616 339 23 180 A O 63 616 335 25 180 A CB 91 621 321 18 181 L N 79 607 348 21 181 L CA 71 596 352 18 181 L C 68 594 367 17 181 L O 61 585 371 20 181 L CB 77 583 346 18 181 L CG 74 581 331 20 181 L CD1 86 574 325 14 181 L CD2 61 573 329 16 182 Y N 74 602 376 19 182 Y CA 71 600 390 20 182 Y C 57 600 394 22 182 Y O 52 590 401 20 182 Y CB 79 611 399 22 182 Y CG 78 608 414 21 182 Y CD1 86 598 419 20 182 Y CD2 70 615 422 20 182 Y CE1 85 594 433 22 182 Y CE2 69 612 436 23 182 Y CZ 76 602 441 23 182 Y OH 76 599 454 25 183 D N 49 609 390 23 183 D CA 35 610 393 23 183 D C 27 598 387 22 183 D O 19 592 394 16 183 D CB 29 623 388 26 183 D CG 16 626 396 25 183 D OD1 14 621 407 27 183 D OD2 8 635 390 27 184 V N 31 594 375 22 184 V CA 25 582 369 20 184 V C 28 569 376 19 184 V O 19 562 379 16 184 V CB 29 581 354 16 184 V CG1 26 567 349 15 184 V CG2 21 591 346 19 185 V N 41 566 379 16 185 V CA 44 554 386 15 185 V C 39 553 400 16 185 V O 37 543 406 19 185 V CB 60 551 386 15 185 V CG1 66 551 371 12 185 V CG2 67 561 394 17 186 S N 36 565 406 18 186 S CA 30 566 419 19 186 S C 15 564 419 23 186 S O 9 558 429 25 186 S CB 33 579 425 16 186 S OG 47 582 426 18 187 T N 8 569 409 23 187 T CA -5 569 408 23 187 T C -13 558 400 23 187 T O -22 552 404 21 187 T CB -10 583 404 25 187 T OG1 -4 593 412 28 187 T CG2 -26 584 406 32 188 L N -7 556 388 22 188 L CA -13 547 379 21 188 L C -15 532 383 20 188 L O -26 526 380 20 188 L CB -6 547 365 24 188 L CG -10 539 352 23 188 L CD1 -4 545 340 25 188 L CD2 -6 525 353 27 189 P N -6 526 390 20 189 P CA -8 512 394 18 189 P C -20 509 403 18 189 P O -27 499 401 19 189 P CB 4 509 402 19 189 P CG 14 519 397 18 189 P CD 6 531 396 17 190 Q N -23 518 413 19 190 Q CA -35 515 421 21 190 Q C -48 517 413 21 190 Q O -58 510 415 20 190 Q CB -35 523 434 22 190 Q CG -46 520 444 30 190 Q CD -59 526 441 31 190 Q OE1 -60 538 437 30 190 Q NE2 -70 518 443 31 191 V N -48 527 404 19 191 V CA -60 530 396 21 191 V C -63 518 387 24 191 V O -75 514 386 25 191 V CB -58 543 388 16 191 V CG1 -70 545 378 17 191 V CG2 -58 555 398 16 192 V N -53 512 381 20 192 V CA -54 501 371 19 192 V C -58 488 377 24 192 V O -65 480 372 19 192 V CB -41 500 362 19 192 V CG1 -42 487 354 17 192 V CG2 -40 512 353 19 193 M N -52 485 389 25 193 M CA -53 472 395 25 193 M C -62 471 408 22 193 M O -64 461 414 21 193 M CB -39 466 398 26 193 M CG -29 470 387 32 193 M SD -11 462 389 33 193 M CE -17 449 404 19 194 G N -66 483 413 21 194 G CA -73 484 425 23 194 G C -66 478 437 27 194 G O -54 480 439 28 195 S N -74 470 445 25 195 S CA -69 463 457 23 195 S C -58 453 454 21 195 S O -51 448 464 23 195 S CB -80 456 464 24 195 S OG -87 447 456 29 196 S N -55 449 442 21 196 S CA -45 439 438 22 196 S C -31 445 438 20 196 S O -21 438 438 21 196 S CB -48 434 424 19 196 S OG -59 425 425 26 197 Y N -30 459 439 19 197 Y CA -17 465 439 19 197 Y C -11 464 453 19 197 Y O -15 471 462 21 197 Y CB -18 480 435 14 197 Y CG -4 486 434 13 197 Y CD1 5 480 427 15 197 Y CD2 -2 499 440 14 197 Y CE1 18 487 426 14 197 Y CE2 9 505 439 18 197 Y CZ 19 499 431 15 197 Y OH 31 506 430 16 198 G N -1 456 455 21 198 G CA 4 454 468 21 198 G C 11 465 475 19 198 G O 10 467 487 20 199 F N 18 474 468 19 199 F CA 25 485 474 18 199 F C 16 496 481 21 199 F O 21 506 486 19 199 F CB 35 492 464 19 199 F CG 46 482 460 16 199 F CD1 55 477 469 19 199 F CD2 47 478 446 18 199 F CE1 66 469 465 17 199 F CE2 58 470 442 16 199 F CZ 67 465 451 17 200 Q N 3 495 480 20 200 Q CA -5 505 486 20 200 Q C -7 502 501 20 200 Q O -12 510 509 21 200 Q CB -18 507 479 20 200 Q CG -28 495 481 21 200 Q CD -40 495 473 20 200 Q OE1 -49 504 474 18 200 Q NE2 -42 486 464 17 201 Y N -3 490 505 21 201 Y CA -5 485 518 19 201 Y C 6 485 527 23 201 Y O 17 482 523 22 201 Y CB -10 470 518 17 201 Y CG -22 467 509 16 201 Y CD1 -34 475 511 18 201 Y CD2 -22 457 500 18 201 Y CE1 -45 472 504 21 201 Y CE2 -34 454 492 22 201 Y CZ -45 462 494 24 201 Y OH -57 459 487 21 202 S N 4 487 540 25 202 S CA 14 487 550 21 202 S C 14 472 554 18 202 S O 4 465 550 20 202 S CB 10 495 563 23 202 S OG 0 489 570 23 203 P N 24 466 560 20 203 P CA 23 452 563 20 203 P C 10 447 570 19 203 P O 5 436 567 21 203 P CB 36 450 572 19 203 P CG 45 460 567 17 203 P CD 36 472 566 18 204 G N 4 455 579 22 204 G CA -7 452 586 21 204 G C -19 452 576 23 204 G O -27 443 577 25 205 Q N -19 462 567 23 205 Q CA -30 463 557 22 205 Q C -29 452 547 24 205 Q O -39 448 541 27 205 Q CB -29 476 551 20 205 Q CG -33 488 560 22 205 Q CD -30 501 554 24 205 Q OE1 -20 503 547 27 205 Q NE2 -38 511 557 23 206 R N -17 447 545 24 206 R CA -15 436 535 21 206 R C -20 423 541 21 206 R O -26 415 534 19 206 R CB 0 434 532 21 206 R CG 3 422 525 20 206 R CD 18 420 523 25 206 R NE 21 417 510 34 206 R CZ 21 405 505 32 206 R NH1 19 394 513 41 206 R NH2 22 403 492 31 207 V N -18 421 554 23 207 V CA -23 409 561 23 207 V C -38 410 562 20 207 V O -45 400 560 20 207 V CB -17 409 576 24 207 V CG1 -23 397 583 24 207 V CG2 -2 408 576 22 208 E N -43 421 564 19 208 E CA -58 423 565 23 208 E C -64 420 552 27 208 E O -74 413 551 28 208 E CB -60 438 569 23 208 E CG -75 442 569 30 208 E CD -77 456 574 37 208 E OE1 -72 465 568 40 208 E OE2 -84 457 585 43 209 F N -58 425 541 26 209 F CA -63 422 528 24 209 F C -63 407 524 24 209 F O -73 401 519 25 209 F CB -55 430 517 28 209 F CG -59 427 503 32 209 F CD1 -71 432 498 31 209 F CD2 -52 418 495 30 209 F CE1 -76 428 485 34 209 F CE2 -56 414 482 31 209 F CZ -68 419 477 33 210 L N -52 400 527 22 210 L CA -51 386 524 21 210 L C -61 377 532 25 210 L O -67 368 527 25 210 L CB -37 381 527 22 210 L CG -26 384 517 21 210 L CD1 -12 383 524 20 210 L CD2 -27 376 505 18 211 V N -62 381 545 27 211 V CA -72 374 554 26 211 V C -86 376 550 23 211 V O -94 366 548 21 211 V CB -70 379 569 28 211 V CG1 -82 375 578 25 211 V CG2 -57 375 575 28 212 N N -90 388 547 24 212 N CA -104 391 542 27 212 N C -107 384 529 30 212 N O -117 378 527 34 212 N CB -106 406 541 23 212 N CG -108 412 555 26 212 N CD1 -112 405 565 29 212 N ND2 -106 425 556 24 213 T N -97 384 520 25 213 T CA -99 377 507 24 213 T C -100 362 509 23 213 T O -109 356 503 28 213 T CB -86 379 497 22 213 T OG1 -85 393 495 19 213 T CG2 -88 372 485 22 214 W N -92 357 518 22 214 W CA -93 342 521 25 214 W C -106 339 526 30 214 W O -112 328 523 31 214 W CB -82 339 531 21 214 W CG -80 324 533 22 214 W CD1 -85 316 542 23 214 W CD2 -71 316 524 24 214 W NE1 -80 303 541 23 214 W CE2 -72 303 530 24 214 W CE3 -64 318 513 20 214 W CZ2 -65 292 524 23 214 W CZ3 -57 307 508 15 214 W CH2 -57 294 513 20 215 K N -112 348 534 32 215 K CA -125 346 541 36 215 K C -137 348 531 37 215 K O -147 342 533 38 215 K CB -127 356 552 33 215 K CG -121 353 565 35 215 K CD -125 364 575 39 215 K CE -120 361 589 41 215 K NZ -123 372 598 44 216 S N -134 355 520 37 216 S CA -145 357 510 36 216 S C -147 345 501 33 216 S O -157 345 494 36 216 S CB -142 370 502 34 216 S OG -131 368 493 34 217 K N -139 335 502 31 217 K CA -141 323 493 34 217 K C -148 312 502 39 217 K O -144 310 513 39 217 K CB -127 318 488 31 217 K CG -117 328 483 29 217 K CD -123 336 471 24 217 K CE -113 347 467 20 217 K NZ -119 358 459 20 218 K N -158 306 496 40 218 K CA -165 295 502 42 218 K C -156 284 506 43 218 K O -158 277 517 45 218 K CB -176 289 493 46 218 K CG -184 300 486 53 218 K CD -196 293 478 55 218 K CE -202 302 467 57 218 K NZ -194 302 454 57 219 N N -146 282 498 43 219 N CA -136 271 500 44 219 N C -123 277 493 42 219 N O -120 273 482 43 219 N CB -141 258 494 48 219 N CG -131 247 496 57 219 N OD1 -125 245 507 62 219 N ND2 -128 239 486 63 220 P N -116 286 500 39 220 P CA -103 292 495 36 220 P C -92 282 492 31 220 P O -90 271 498 32 220 P CB -100 302 505 35 220 P CG -104 296 518 37 220 P CD -117 290 514 37 221 M N -84 286 482 28 221 M CA -72 279 478 26 221 M C -63 291 473 25 221 M O -68 300 468 22 221 M CB -75 269 467 28 221 M CG -62 262 461 32 221 M SD -52 273 448 35 221 M CE -56 263 430 39 222 G N -50 290 477 22 222 G CA -41 301 473 22 222 G C -28 295 468 20 222 G O -25 283 471 21 223 F N -20 303 460 22 223 F CA -7 299 456 21 223 F C 0 311 452 22 223 F O -4 322 450 23 223 F CB -8 289 443 22 223 F CG -13 296 431 24 223 F CD1 -5 301 422 22 223 F CD2 -27 296 428 25 223 F CE1 -9 307 410 26 223 F CE2 -32 302 416 27 223 F CZ -23 308 407 23 224 S N 13 309 453 22 224 S CA 22 320 450 22 224 S C 29 316 437 19 224 S O 29 304 434 19 224 S CB 33 322 461 18 224 S OG 40 310 464 19 225 Y N 32 325 429 20 225 Y CA 38 322 416 25 225 Y C 52 329 416 23 225 Y O 53 341 419 24 225 Y CB 30 326 404 25 225 Y CG 35 320 390 25 225 Y CD1 33 307 387 22 225 Y CD2 43 328 382 26 225 Y CE1 38 301 375 23 225 Y CE2 48 323 370 20 225 Y CZ 46 309 367 20 225 Y OH 51 304 355 19 226 D N 62 321 412 26 226 D CA 76 327 411 28 226 D C 81 325 397 24 226 D O 82 314 392 22 226 D CB 85 320 421 32 226 D CG 100 323 419 34 226 D OD1 103 335 418 37 226 D OD2 108 314 418 38 227 T N 83 336 390 23 227 T CA 89 336 377 25 227 T C 104 336 377 25 227 T O 110 344 384 26 227 T CB 84 349 369 29 227 T OG1 70 349 368 23 227 T CG2 90 349 354 22 228 R N 110 327 370 27 228 R CA 124 325 369 32 228 R C 131 338 362 33 228 R O 128 340 351 38 228 R CB 128 313 360 35 228 R CG 142 313 355 45 228 R CD 143 303 343 54 228 R NE 143 289 348 64 228 R CZ 133 280 344 65 228 R NH1 123 284 336 65 228 R NH2 134 268 349 64 229 C N 138 345 370 31 229 C CA 145 357 365 31 229 C C 135 366 357 29 229 C O 137 369 345 26 229 C CB 157 353 357 33 229 C SG 167 366 351 47 230 F N 125 371 364 25 230 F CA 114 380 358 23 230 F C 120 391 349 22 230 F O 115 392 338 21 230 F CB 105 386 369 21 230 F CG 93 393 363 17 230 F CD1 93 406 359 13 230 F CD2 81 386 363 21 230 F CE1 81 412 355 15 230 F CE2 69 392 358 16 230 F CZ 69 405 354 13 231 D N 130 398 354 20 231 D CA 136 409 346 20 231 D C 140 405 332 18 231 D O 138 412 322 17 231 D CB 148 415 353 22 231 D CG 144 426 363 23 231 D OD1 132 427 367 23 231 D OD2 153 434 367 20 232 S N 145 393 330 18 232 S CA 150 388 317 22 232 S C 138 382 309 24 232 S O 140 381 296 26 232 S CB 160 377 319 24 232 S OG 172 383 323 28 233 T N 127 379 315 25 233 T CA 115 374 307 21 233 T C 108 386 301 19 233 T O 99 384 292 18 233 T CB 106 365 316 21 233 T OG1 99 374 326 19 233 T CG2 113 354 323 21 234 V N 110 398 306 15 234 V CA 104 410 300 15 234 V C 109 414 286 19

234 V O 121 417 285 19 234 V CB 105 422 310 14 234 V CG1 100 435 304 13 234 V CG2 98 418 323 15 235 T N 101 413 277 18 235 T CA 103 415 262 17 235 T C 101 429 258 17 235 T O 95 437 265 15 235 T CB 95 406 254 17 235 T OG1 81 410 255 19 235 T CG2 96 391 259 14 236 E N 105 432 245 17 236 E CA 102 446 239 16 236 E C 87 448 238 9 236 E O 83 459 240 11 236 E CB 109 447 225 14 236 E CG 106 461 219 21 236 E CD 113 462 205 26 236 E OE1 125 458 204 29 236 E OE2 108 469 196 28 237 N N 80 438 235 11 237 N CA 65 439 234 17 237 N C 60 444 248 17 237 N O 54 454 249 17 237 N CB 59 425 230 16 237 N CG 44 425 233 23 237 N OD1 36 431 225 22 237 N ND2 40 419 244 18 238 D N 64 437 258 19 238 D CA 60 440 272 17 238 D C 63 455 276 16 238 D O 54 461 280 20 238 D CB 68 431 282 20 238 D CG 64 417 281 19 238 D OD1 53 414 275 21 238 D OD2 71 408 286 20 239 I N 75 459 273 16 239 I CA 79 473 275 14 239 I C 71 483 267 14 239 I O 67 494 272 16 239 I CB 94 475 274 10 239 I CG1 102 468 285 16 239 I CG2 98 490 274 8 239 I CD1 114 460 280 15 240 R N 67 480 255 19 240 R CA 59 489 246 19 240 R C 44 489 251 13 240 R O 38 499 251 14 240 R CB 60 485 232 18 240 R CG 73 488 225 22 240 R CD 73 485 210 24 240 R NE 86 488 204 20 240 R CZ 91 500 201 17 240 R NH1 85 511 204 17 240 R NH2 104 500 197 19 241 V N 39 477 256 15 241 V CA 26 476 261 14 241 V C 25 485 274 15 241 V O 16 493 276 17 241 V CB 22 462 264 12 241 V CG1 9 461 273 18 241 V CG2 19 454 251 11 242 E N 36 485 282 19 242 E CA 37 494 293 15 242 E C 36 509 289 14 242 E O 29 517 296 13 242 E CB 50 492 301 11 242 E CG 51 479 308 15 242 E CD 65 475 311 18 242 E OE1 74 483 311 20 242 E OE2 67 463 314 24 243 E N 42 512 279 18 243 E CA 42 526 275 17 243 E C 28 530 270 14 243 E O 23 541 272 14 243 E CB 52 529 264 16 243 E CG 55 544 262 20 243 E CD 56 548 248 25 243 E OE1 62 541 240 33 243 E OE2 51 559 244 25 244 S N 21 521 263 17 244 S CA 7 524 258 19 244 S C -1 526 270 20 244 S O -10 535 269 20 244 S CB 2 513 249 16 244 S OG 0 501 256 21 245 I N 0 519 281 21 245 I CA -7 521 293 16 245 I C -5 535 299 18 245 I O -14 542 301 19 245 I CB -5 510 303 16 245 I CG1 -7 496 296 13 245 I CG2 -13 512 316 14 245 I CD1 -3 484 304 18 246 Y N 7 538 300 19 246 Y CA 11 552 306 18 246 Y C 5 562 297 20 246 Y O 0 573 301 20 246 Y CB 26 554 306 17 246 Y CG 34 544 313 19 246 Y CD1 30 536 323 18 246 Y CD2 48 542 309 17 246 Y CE1 38 527 330 20 246 Y CE2 56 533 315 19 246 Y CZ 51 525 325 19 246 Y OH 59 515 331 19 247 Q N 5 560 283 19 247 Q CA 0 570 274 20 247 Q C -14 572 274 21 247 Q O -19 581 268 21 247 Q CB 5 567 260 20 247 Q CG 20 569 257 19 247 Q CD 26 583 258 19 247 Q OE1 18 593 260 21 247 Q NE2 39 585 257 22 248 C N -21 563 281 22 248 C CA -36 564 283 21 248 C C -39 576 292 21 248 C O -50 582 291 26 248 C CB -42 551 288 19 248 C SG -43 538 276 22 249 C N -30 578 302 20 249 C CA -32 589 311 19 249 C C -34 603 305 22 249 C O -31 604 293 26 249 C CB -20 590 321 17 249 C SG -17 575 330 21 250 D N -40 612 312 19 250 D CA -41 626 307 21 250 D C -28 632 311 20 250 D O -26 635 323 22 250 D CB -53 632 315 25 250 D CG -55 647 311 27 250 D OD1 -46 653 306 34 250 D OD2 -66 652 314 34 251 L N -19 634 301 23 251 L CA -6 640 303 21 251 L C -3 653 294 22 251 L O -9 655 284 23 251 L CB 4 630 300 18 251 L CG 3 616 306 20 251 L CD1 9 606 296 20 251 L CD2 11 616 319 22 252 A N 5 661 299 23 252 A CA 10 672 291 26 252 A C 17 667 279 29 252 A O 24 656 280 28 252 A CB 20 681 300 24 253 P N 16 673 267 31 253 P CA 22 668 255 29 253 P C 38 667 257 26 253 P O 44 658 251 23 253 P CB 19 679 245 32 253 P CG 5 683 249 31 253 P CD 7 684 264 32 254 E N 44 675 265 29 254 E CA 58 674 268 27 254 E C 62 662 276 27 254 E O 72 656 274 28 254 E CB 62 687 276 28 254 E CG 78 688 278 31 254 E CD 82 700 285 34 254 E OE1 75 705 294 41 254 E OE2 92 706 281 38 255 A N 52 657 284 24 255 A CA 55 645 292 22 255 A C 52 632 283 18 255 A O 59 622 284 18 255 A CB 45 644 304 20 256 R N 43 633 273 19 256 R CA 40 622 264 19 256 R C 53 620 256 17 256 R O 56 608 253 18 256 R CB 29 625 255 18 256 R CG 16 628 261 21 256 R CD 5 628 251 24 256 R NE -8 629 258 26 256 R CZ -14 619 263 24 256 R NH1 -8 607 264 23 256 R NH2 -26 621 269 23 257 Q N 59 631 252 18 257 Q CA 71 631 243 21 257 Q C 83 625 251 16 257 Q O 89 615 247 17 257 Q CB 75 645 238 19 257 Q CG 87 645 229 21 257 Q CD 85 639 215 22 257 Q OE1 75 632 213 23 257 Q NE2 94 642 206 28 258 A N 84 630 263 19 258 A CA 95 625 272 17 258 A C 93 610 275 17 258 A O 103 602 276 18 258 A CB 96 633 285 15 259 I N 81 605 277 16 259 I CA 78 591 280 15 259 I C 81 582 268 19 259 I O 86 571 269 19 259 I CB 64 589 285 18 259 I CG1 62 596 299 17 259 I CG2 61 574 287 18 259 I CD1 48 597 304 19 260 K N 77 587 256 18 260 K CA 79 580 244 19 260 K C 94 578 242 14 260 K O 99 567 239 14 260 K CB 73 587 232 22 260 K CG 76 582 218 23 260 K CD 67 589 208 27 260 K CE 70 585 194 37 260 K NZ 82 592 189 40 261 S N 101 589 243 16 261 S CA 116 590 242 17 261 S C 123 580 252 18 261 S O 131 572 247 15 261 S CB 120 604 243 16 261 S OG 134 606 240 24 262 L N 120 581 265 17 262 L CA 126 573 275 15 262 L C 123 558 272 14 262 L O 132 550 274 15 262 L CB 121 576 289 14 262 L CG 127 589 296 16 262 L CD1 119 593 308 14 262 L CD2 142 587 299 16 263 T N 111 555 267 14 263 T CA 108 542 263 14 263 T C 117 536 252 14 263 T O 122 525 253 18 263 T CB 93 540 259 16 263 T OG1 85 543 271 19 263 T CG2 90 525 255 12 264 E N 118 544 241 16 264 E CA 126 540 230 18 264 E C 141 538 233 16 264 E O 147 528 232 20 264 E CB 124 550 218 19 264 E CG 111 551 211 29 264 E CD 105 539 204 30 264 E OE1 113 530 200 31 264 E OE2 93 538 203 35 265 R N 146 549 238 16 265 R CA 160 551 241 15 265 R C 165 544 253 19 265 R O 177 540 254 20 265 R CB 163 566 242 13 265 R CG 158 573 230 12 265 R CD 161 588 231 11 265 R NE 175 591 233 16 265 R CZ 180 603 235 15 265 R NH1 172 613 235 16 265 R NH2 193 604 236 18 266 L N 157 542 264 18 266 L CA 162 536 276 17 266 L C 155 523 281 16 266 L O 161 512 282 14 266 L CB 162 546 288 16 266 L CG 166 543 302 14 266 L CD1 180 538 303 15 266 L CD2 163 555 310 13 267 Y N 142 523 282 17 267 Y CA 134 512 287 16 267 Y C 134 499 279 15 267 Y O 136 488 285 15 267 Y CB 120 516 291 16 267 Y CG 119 528 300 17 267 Y CD1 130 529 310 14 267 Y CD2 109 537 300 13 267 Y CE1 130 540 319 15 267 Y CE2 109 548 309 14 267 Y CZ 119 549 319 16 267 Y OH 120 559 328 14 268 I N 133 500 266 15 268 I CA 133 488 258 15 268 I C 147 481 258 15 268 I O 147 469 257 15 268 I CB 128 492 243 20 268 I CG1 114 496 243 20 268 I CG2 131 481 233 24 268 I CD1 109 502 230 25 269 G N 158 489 258 17 269 G CA 171 482 257 14 269 G C 182 493 256 12 269 G O 179 505 256 13 270 G N 194 488 255 15 270 G CA 205 497 255 16 270 G C 219 491 258 17 270 G O 220 480 263 17 271 P N 230 498 254 19 271 P CA 243 493 257 20 271 P C 247 493 272 19 271 P O 243 501 279 15 271 P CB 253 502 248 19 271 P CG 246 515 249 23 271 P CD 231 511 247 20 272 L N 254 482 276 21 272 L CA 259 480 289 20 272 L C 274 484 290 22 272 L O 282 477 284 25 272 L CB 256 465 293 18 272 L CG 242 460 291 14 272 L CD1 242 445 291 10 272 L CD2 233 466 301 19 273 T N 277 493 299 21 273 T CA 291 498 300 22 273 T C 296 495 315 24 273 T O 290 498 325 24 273 T CB 292 513 298 23 273 T OG1 288 516 284 26 273 T CG2 307 518 300 24 274 N N 307 487 316 22 274 N CA 313 484 329 19 274 N C 319 497 336 20 274 N O 320 507 330 21 274 N CB 323 472 329 19 274 N CG 337 476 323 15 274 N OD1 342 487 323 18 274 N ND2 345 466 320 14 275 S N 323 495 349 23 275 S CA 329 507 356 24 275 S C 342 513 351 27 275 S O 345 524 355 28 275 S CB 330 503 371 29 275 S OG 340 493 373 29 276 K N 349 505 342 28 276 K CA 361 510 337 29 276 K C 359 517 323 29 276 K O 368 523 317 27 276 K CB 371 499 335 31 276 K CG 376 493 348 37 276 K CD 387 483 346 43 276 K CE 384 472 337 48 276 K NZ 394 461 335 49 277 G N 346 518 319 30 277 G CA 342 524 307 27 277 G C 343 515 294 27 277 G O 342 520 283 30 278 Q N 344 502 296 27 278 Q CA 344 493 285 28 278 Q C 330 487 282 30 278 Q O 322 484 291 25 278 Q CB 353 481 287 35 278 Q CG 367 484 292 41 278 Q CD 374 471 296 46 278 Q OE1 375 467 307 47 278 Q NE2 380 465 286 49 279 N N 326 486 269 27 279 N CA 314 480 266 25 279 N C 313 465 268 25 279 N O 320 457 262 23 279 N CB 311 483 251 28 279 N CG 298 477 246 31 279 N OD1 298 470 236 36 279 N ND2 287 479 253 36 280 C N 304 461 277 21 280 C CA 302 447 281 22 280 C C 292 440 272 19 280 C O 291 427 272 19 280 C CB 297 445 295 24 280 C SG 310 451 307 33 281 G N 283 447 265 21 281 G CA 273 441 257 20 281 G C 261 449 254 18 281 G O 261 462 255 17 282 Y N 249 442 253 21 282 Y CA 237 449 250 18 282 Y C 225 442 257 18 282 Y O 224 430 257 20 282 Y CB 234 449 235 19 282 Y CG 226 461 231 21 282 Y CD1 231 473 229 16 282 Y CD2 212 460 228 23 282 Y CE1 224 484 225 20 282 Y CE2 204 470 224 15 282 Y CZ 210 483 222 21 282 Y OH 202 493 219 26 283 R N 216 450 263 20 283 R CA 204 446 270 19 283 R C 191 448 262 22 283 R O 190 459 255 24 283 R CB 204 453 283 22 283 R CG 190 454 290 22 283 R CD 191 466 299 21 283 R NE 178 472 299 29 283 R CZ 175 485 295 21 283 R NH1 184 493 291 16 283 R NH2 162 489 295 27 284 R N 182 438 262 23 284 R CA 170 439 255 24 284 R C 158 434 264 22 284 R O 149 428 260 25 284 R CB 170 431 242 21 284 R CG 180 437 231 28 284 R CD 179 429 218 35 284 R NE 192 431 211 45 284 R CZ 194 441 203 53 284 R NH1 185 451 201 54 284 R NH2 206 442 197 55 285 C N 160 437 277 20 285 C CA 150 432 287 17 285 C C 149 443 297 11 285 C O 155 454 295 13 285 C CB 154 419 293 20 285 C SG 170 419 302 16 286 R N 142 441 308 14 286 R CA 141 451 318 15 286 R C 154 455 325 16 286 R O 161 446 329 17 286 R CB 131 447 329 17 286 R CG 131 455 342 14 286 R CD 120 467 341 17 286 R NE 107 461 341 20 286 R CZ 97 464 333 18 286 R NH1 99 474 324 21 286 R NH2 86 458 333 19 287 A N 156 468 326 16 287 A CA 168 474 333 13 287 A C 163 474 348 18 287 A O 152 478 351 17 287 A CB 171 488 329 10 288 S N 172 469 357 19 288 S CA 169 469 371 21 288 S C 170 482 378 20 288 S O 164 484 389 23 288 S CB 177 458 378 23 288 S OG 191 462 377 27 289 G N 177 492 372 18 289 G CA 179 505 378 14 289 G C 172 517 372 16 289 G O 179 527 370 17 290 V N 159 516 369 17 290 V CA 152 527 363 16 290 V C 139 530 372 16 290 V O 135 521 379 15 290 V CB 148 526 348 13 290 V CG1 161 527 339 13 290 V CG2 141 513 345 8 291 L N 134 542 370 17 291 L CA 122 546 378 18 291 L C 110 537 375 20 291 L O 103 533 385 20 291 L CB 118 560 375 13 291 L CG 107 566 383 17 291 L CD1 109 565 398 18 291 L CD2 105 581 380 19 292 T N 109 532 363 20 292 T CA 98 523 360 19 292 T C 99 508 362 19 292 T O 90 501 359 19 292 T CB 94 525 345 18 292 T OG1 106 524 337 20 292 T CG2 88 539 342 16 293 T N 110 504 368 15 293 T CA 112 490 371 14 293 T C 101 483 379 14 293 T O 95 473 376 16 293 T CB 127 487 377 17 293 T OG1 137 492 369 21 293 T CG2 129 472 380 14 294 S N 97 490 390 14 294 S CA 86 485 399 15 294 S C 73 485 392 15 294 S O 66 475 391 14 294 S CB 86 493 412 14 294 S OG 78 487 422 17 295 C N 69 497 387 15 295 C CA 56 499 380 17 295 C C 54 489 368 18 295 C O 44 482 367 18 295 C CB 54 513 377 14 295 C SG 37 517 370 24 296 G N 64 489 359 18 296 G CA 63 481 347 14 296 G C 63 467 351 16 296 G O 55 459 345 16 297 N N 71 462 361 16 297 N CA 70 448 365 15 297 N C 57 445 371 12 297 N O 52 434 368 14 297 N CB 81 445 376 18 297 N CG 95 442 369 25 297 N OD1 96 441 357 21 297 N ND2 105 439 378 20 298 T N 51 454 379 14 298 T CA 37 451 385 16 298 T C 27 450 374 15 298 T O 19 441 373 17 298 T CB 34 461 396 21 298 T OG1 45 463 405 23 298 T CG2 22 456 404 18 299 L N 26 460 365 16 299 L CA 17 460 354 18 299 L C 18 448 345 20 299 L O 7 441 342 19 299 L CB 19 473 345 15 299 L CG 14 486 351 15 299 L CD1 17 497 341 19 299 L CD2 0 485 353 17 300 T N 30 444 342 19 300 T CA 32 432 333 16 300 T C 29 419 340 15 300 T O 24 410 335 15 300 T CB 47 433 327 21 300 T OG1 48 443 318 25 300 T CG2 50 420 320 21 301 C N 33 418 353 16 301 C CA 30 406 361 15 301 C C 14 405 362 11 301 C O 9 394 359 15 301 C CB 36 407 375 15 301 C SG 34 391 384 21 302 Y N 8 416 365 12 302 Y CA -6 416 366 18 302 Y C -13 412 353 17 302 Y O -23 405 352 17 302 Y CB -11 429 371 18 302 Y CG -26 431 372 20 302 Y CD1 -33 427 384 23 302 Y CD2 -33 437 362 23 302 Y CE1 -46 429 385 25 302 Y CE2 -47 439 363 24 302 Y CZ -54 435 375 25 302 Y OH -67 437 376 25 303 L N -8 418 342 17 303 L CA -14 416 328 17 303 L C -13 401 325 18 303 L O -23 395 323 18 303 L CB -6 424 318 15 303 L CG -9 422 303 18 303 L CD1 -24 422 300 11 303 L CD2 -2 433 295 13 304 K N -1 395 325 17 304 K CA 0 381 322 15 304 K C -6 372 332 18 304 K O -11 361 328 18 304 K CB 15 378 322 15 304 K CG 23 386 311 13 304 K CD 38 381 310 11 304 K CE 46 390 301 13 304 K NZ 60 385 299 15 305 A N -6 376 345 16 305 A CA -12 367 355 18 305 A C -27 367 354 15 305 A O -34 356 354 18 305 A CB -8 371 369 22 306 S N -33 379 352 17 306 S CA -48 380 350 19 306 S C -53 372 338 20 306 S O -62 364 339 15 306 S CB -52 394 348 18 306 S OG -49 403 359 22 307 A N -46 373 327 18 307 A CA -49 366 315 15 307 A C -47 351 316 17 307 A O -55 343 311 21 307 A CB -40 371 303 13 308 A N -37 346 324 16 308 A CA -34 332 326 14 308 A C -45 326 335 14 308 A O -48 314 334 16 308 A CB -21 330 332 15 309 C N -51 334 344 19 309 C CA -61 329 353 22 309 C C -74 326 344 20 309 C O -80 315 346 23 309 C CB -65 340 363 21 309 C SG -54 342 377 27 310 R N -77 335 335 24 310 R CA -88 332 326 22 310 R C -85 320 317 23 310 R O -93 311 316 24 310 R CB -90 345 317 17 310 R CG -93 357 325 16 310 R CD -97 368 316 14 310 R NE -99 380 324 18 310 R CZ -105 391 320 19 310 R NH1 -109 393 307 25 310 R NH2 -106 402 328 22 311 A N -72 319 312 25 311 A CA -68 307 305 25 311 A C -69 294 313 27 311 A O -73 284 307 27 311 A CB -54 309 300 24 312 A N -66 294 325 26 312 A CA -66 282 334 27

312 A C -80 280 339 27 312 A O -83 269 346 26 312 A CB -56 284 345 29 313 K N -89 289 337 29 313 K CA -103 289 342 30 313 K C -104 288 357 30 313 K O -112 280 362 29 313 K CB -111 277 335 33 313 K CG -111 278 320 36 313 K CD -116 264 314 39 313 K CE -106 254 315 48 313 K NZ -110 241 309 53 314 L N -96 296 363 29 314 L CA -96 297 378 29 314 L C -109 304 383 29 314 L O -113 314 376 33 314 L CB -83 304 383 28 314 L CG -71 296 387 29 314 L CD1 -69 285 377 32 314 L CD2 -58 304 388 26 315 Q N -115 299 393 31 315 Q CA -128 305 398 35 315 Q C -126 317 408 33 315 Q O -119 315 419 33 315 Q CB -136 294 405 42 315 Q CG -144 285 395 50 315 Q CD -155 293 388 56 315 Q OE1 -154 297 377 58 315 Q NE2 -166 295 395 57 316 D N -133 328 406 35 316 D CA -133 340 415 37 316 D C -119 342 420 37 316 D O -116 340 432 37 316 D CB -143 338 427 39 316 D CG -145 351 435 46 316 D OD1 -139 362 431 52 316 D OD2 -152 351 445 50 317 C N -110 347 411 35 317 C CA -96 350 415 30 317 C C -94 364 420 28 317 C O -100 373 415 27 317 C CB -87 348 403 28 317 C SG -87 332 397 30 318 T N -86 364 431 26 318 T CA -82 377 436 26 318 T C -67 376 437 25 318 T O -61 366 442 26 318 T CB -87 379 451 27 318 T OG1 -101 376 451 30 318 T CG2 -85 393 455 21 319 M N -60 386 431 24 319 M CA -45 386 431 26 319 M C -39 397 439 22 319 M O -46 407 442 20 319 M CB -40 386 417 28 319 M CG -45 374 409 36 319 M SD -40 377 389 41 319 M CE -31 395 390 34 320 L N -27 395 443 23 320 L CA -19 405 450 21 320 L C -6 406 443 18 320 L O 0 395 442 18 320 L CB -18 401 465 20 320 L CG -12 412 474 19 320 L CD1 -20 425 472 18 320 L CD2 -11 407 488 23 321 V N -2 417 437 20 321 V CA 9 418 430 19 321 V C 18 429 435 16 321 V O 14 441 438 16 321 V CB 6 421 414 18 321 V CG1 18 419 406 17 321 V CG2 -5 412 410 18 322 N N 31 426 436 17 322 N CA 42 436 441 19 322 N C 53 433 431 19 322 N O 61 425 433 19 322 N CB 47 432 455 21 322 N CG 37 435 465 22 322 N OD1 27 427 467 26 322 N ND2 39 446 473 23 323 G N 53 441 420 20 323 G CA 64 439 410 19 323 G C 62 425 404 20 323 G O 52 421 400 20 324 D N 73 417 405 21 324 D CA 74 404 400 19 324 D C 68 393 409 22 324 D O 69 381 407 23 324 D CB 88 400 396 25 324 D CG 97 398 409 29 324 D OD1 98 407 417 28 324 D OD2 103 387 410 36 325 D N 64 398 421 22 325 D CA 59 388 431 23 325 D C 43 388 430 19 325 D O 36 398 430 15 325 D CB 63 393 445 27 325 D CG 64 381 455 35 325 D OD1 54 375 458 39 325 D OD2 76 378 458 38 326 L N 39 375 429 17 326 L CA 24 373 427 21 326 L C 18 363 436 18 326 L O 24 352 439 19 326 L CB 22 367 412 22 326 L CG 8 362 409 23 326 L CD1 -1 374 409 22 326 L CD2 8 356 395 24 327 V N 6 365 441 21 327 V CA -1 356 449 22 327 V C -15 357 444 21 327 V O -21 367 441 18 327 V CB 0 360 464 20 327 V CG1 -12 365 470 27 327 V CG2 5 348 472 21 328 V N -21 345 443 23 328 V CA -35 343 438 25 328 V C -43 335 448 24 328 V O -39 324 452 27 328 V CB -35 335 424 24 328 V CG1 -50 334 420 23 328 V CG2 -28 343 413 26 329 I N -55 341 451 27 329 I CA -65 334 460 26 329 I C -77 333 452 28 329 I O -82 342 445 26 329 I CB -67 342 473 27 329 I CG1 -54 343 482 25 329 I CG2 -79 336 481 21 329 I CD1 -55 352 493 24 330 C N -83 321 452 30 330 C CA -95 318 444 32 330 C C -104 308 451 34 330 C O -101 303 462 33 330 C CB -90 312 430 29 330 C SG -81 296 432 31 331 E N -114 304 444 34 331 E CA -124 294 449 33 331 E C -120 281 445 32 331 E O -117 278 433 36 331 E CB -138 298 443 31 331 E CG -150 292 449 33 331 E CD -152 297 463 31 331 E OE1 -156 309 465 28 331 E OE2 -151 289 472 31 332 S N -118 272 454 32 332 S CA -113 258 452 33 332 S C -123 249 444 38 332 S O -136 251 446 40 332 S CB -109 251 464 33 332 S OG -105 238 462 30 333 A N -119 240 436 38 333 A CA -127 231 429 39 333 A C -122 216 431 40 333 A O -124 208 423 46 333 A CB -126 234 414 35 334 G N -116 214 443 37 334 G CA -111 201 446 36 334 G C -96 200 444 37 334 G O -91 206 434 39 335 V N -89 193 453 37 335 V CA -75 191 452 41 335 V C -69 187 438 42 335 V O -60 193 433 42 335 V CB -69 182 464 41 335 V CG1 -77 169 464 44 335 V CG2 -54 180 462 44 336 Q N -76 177 432 45 336 Q CA -71 171 419 45 336 Q C -74 181 408 44 336 Q O -66 182 398 41 336 Q CB -78 158 416 49 336 Q CG -74 147 426 53 336 Q CD -58 146 428 59 336 Q OE1 -51 147 418 63 336 Q NE2 -54 143 440 63 337 E N -85 188 409 40 337 E CA -88 198 399 39 337 E C -79 210 401 41 337 E O -74 216 391 40 337 E CB -103 202 400 38 337 E CG -108 211 388 43 337 E CD -105 206 374 46 337 E OE1 -106 194 371 41 337 E OE2 -101 214 365 49 338 D N -76 214 413 40 338 D CA -67 225 417 34 338 D C -53 223 411 31 338 D O -47 233 407 31 338 D CB -67 228 432 30 338 D CG -80 234 437 31 338 D OD1 -89 238 429 34 338 D OD2 -82 236 449 31 339 A N -48 211 411 29 339 A CA -35 208 406 30 339 A C -35 209 391 33 339 A O -26 214 384 35 339 A CB -31 194 410 30 340 A N -47 206 385 32 340 A CA -48 207 370 31 340 A C -49 221 366 29 340 A O -42 225 356 27 340 A CB -61 199 366 28 341 S N -56 230 373 28 341 S CA -58 244 370 29 341 S C -44 251 371 30 341 S O -42 261 363 29 341 S CB -68 250 379 28 341 S OG -80 244 377 34 342 L N -36 247 380 31 342 L CA -22 253 382 29 342 L C -13 250 371 27 342 L O -5 259 367 28 342 L CB -16 249 395 28 342 L CG -17 259 407 25 342 L CD1 -7 255 418 22 342 L CD2 -14 272 402 28 343 R N -14 238 366 26 343 R CA -5 234 354 29 343 R C -10 242 342 27 343 R O -1 246 334 26 343 R CB -7 219 351 31 343 R CG 5 210 355 41 343 R CD 2 195 353 47 343 R NE -5 193 341 58 343 R CZ -16 187 340 64 343 R NH1 -22 182 351 67 343 R NH2 -23 186 328 66 344 A N -23 245 341 27 344 A CA -28 253 330 24 344 A C -24 267 331 24 344 A O -20 274 321 24 344 A CB -43 252 329 23 345 F N -24 272 344 24 345 F CA -20 286 346 22 345 F C -5 288 343 20 345 F O -1 297 336 23 345 F CB -22 289 361 16 345 F CG -17 303 365 17 345 F CD1 -4 305 370 17 345 F CD2 -26 314 365 16 345 F CE1 0 318 373 19 345 F CE2 -22 327 368 15 345 F CZ -9 329 373 17 346 T N 3 278 347 20 346 T CA 17 279 345 23 346 T C 20 278 330 23 346 T O 28 286 325 24 346 T CB 24 267 352 22 346 T OG1 21 268 366 24 346 T CG2 39 268 349 21 347 E N 13 270 323 23 347 E CA 14 268 308 21 347 E C 11 281 301 20 347 E O 17 285 292 22 347 E CB 5 257 303 21 347 E CG 11 243 307 26 347 E CD 1 232 305 35 347 E OE1 -10 234 301 38 347 E OE2 5 220 308 40 348 A N 1 288 307 17 348 A CA -2 301 301 17 348 A C 7 311 303 18 348 A O 11 318 294 21 348 A CB -16 305 306 17 349 M N 12 311 316 21 349 M CA 23 321 319 17 349 M C 35 318 311 16 349 M O 42 328 307 16 349 M CB 27 319 334 20 349 M CG 17 324 344 12 349 M SD 14 344 343 22 349 M CE 31 352 352 21 350 T N 38 306 308 14 350 T CA 50 302 300 21 350 T C 48 308 285 24 350 T O 58 314 280 21 350 T CB 52 287 299 21 350 T OG1 53 282 313 25 350 T CG2 64 284 291 22 351 R N 36 307 279 22 351 R CA 34 312 266 20 351 R C 36 327 265 18 351 R O 39 332 255 20 351 R CB 20 309 261 19 351 R CG 17 295 257 19 351 R CD 3 294 252 22 351 R NE -2 282 258 34 351 R CZ -12 281 267 30 351 R NH1 -17 292 272 30 351 R NH2 -15 269 272 33 352 Y N 33 333 276 19 352 Y CA 34 348 277 16 352 Y C 48 352 281 16 352 Y O 51 363 284 20 352 Y CB 25 353 288 18 352 Y CG 10 351 286 22 352 Y CD1 5 351 273 21 352 Y CD2 1 349 297 21 352 Y CE1 -8 349 271 22 352 Y CE2 -11 347 295 23 352 Y CZ -17 348 282 23 352 Y OH -30 347 281 24 353 S N 57 342 281 21 353 S CA 71 344 284 26 353 S C 75 345 299 28 353 S O 85 351 302 35 353 S CB 78 354 276 21 353 S OG 79 367 282 28 354 A N 66 340 308 26 354 A CA 69 341 322 26 354 A C 70 327 328 27 354 A O 62 323 337 26 354 A CB 59 349 329 23 355 P N 80 319 324 28 355 P CA 81 305 330 27 355 P C 84 306 344 29 355 P O 89 316 350 27 355 P CB 93 300 321 23 355 P CG 101 312 320 26 355 P CD 92 322 316 29 356 P N 81 295 352 32 356 P CA 83 294 366 32 356 P C 97 289 370 33 356 P O 104 283 363 35 356 P CB 73 284 370 34 356 P CG 73 274 359 31 356 P CD 73 284 347 34 357 G N 101 294 382 33 357 G CA 114 289 388 36 357 G C 110 277 395 40 357 G O 114 266 392 41 358 D N 102 279 406 43 358 D CA 97 268 414 45 358 D C 83 265 409 42 358 D O 75 274 407 41 358 D CB 97 271 429 49 358 D CG 110 274 435 52 358 D OD1 119 264 434 56 358 D OD2 113 285 440 55 359 P N 80 252 408 41 359 P CA 66 248 403 41 359 P C 56 253 413 38 359 P O 57 251 425 40 359 P CB 66 233 403 43 359 P CG 81 230 400 42 359 P CD 88 240 409 41 360 P N 46 261 409 36 360 P CA 35 266 418 33 360 P C 29 254 426 34 360 P O 29 243 421 35 360 P CB 25 272 409 35 360 P CG 33 276 396 35 360 P CD 42 264 395 33 361 Q N 24 257 438 37 361 Q CA 18 247 446 36 361 Q C 5 252 452 30 361 Q O 5 262 459 27 361 Q CB 28 242 457 43 361 Q CG 25 230 464 57 361 Q CD 35 226 474 64 361 Q OE1 33 227 486 67 361 Q NE2 47 222 469 67 362 P N -5 244 451 29 362 P CA -18 248 457 27 362 P C -17 247 472 25 362 P O -13 237 478 26 362 P CB -28 238 451 26 362 P CG -21 231 440 25 362 P CD -7 231 444 28 363 E N -22 258 479 25 363 E CA -21 258 493 27 363 E C -35 260 499 28 363 E O -43 268 494 25 363 E CB -11 269 499 28 363 E CG 2 266 496 29 363 E CD 8 254 505 33 363 E OE1 1 249 514 33 363 E OE2 20 250 503 33 364 Y N -38 253 510 31 364 Y CA -51 254 516 34 364 Y C -51 260 530 34 364 Y O -61 260 538 34 364 Y CB -59 240 516 35 364 Y CG -60 235 502 37 364 Y CD1 -71 238 494 36 364 Y CD2 -50 226 497 35 364 Y CE1 -72 234 481 34 364 Y CE2 -51 222 483 34 364 Y CZ -62 226 476 34 364 Y OH -62 222 462 38 365 D N -39 264 534 35 365 D CA -36 271 547 35 365 D C -30 284 544 33 365 D O -19 284 538 34 365 D CB -27 262 555 40 365 D CG -25 267 570 48 365 D OD1 -28 279 573 50 365 D OD2 -19 259 578 53 366 L N -37 295 547 32 366 L CA -32 308 544 34 366 L C -18 311 549 34 366 L O -9 316 542 34 366 L CB -41 319 549 32 366 L CG -37 333 547 34 366 L CD1 -34 336 532 35 366 L CD2 -48 343 552 33 367 E N -15 307 562 34 367 E CA -2 308 568 35 367 E C 8 301 561 34 367 E O 20 304 563 30 367 E CB -3 303 583 40 367 E CG -13 310 592 45 367 E CD -13 305 606 49 367 E OE1 -2 302 611 51 367 E OE2 -23 304 612 52 368 L N 5 292 552 34 368 L CA 15 284 545 33 368 L C 19 290 531 32 368 L O 26 284 524 32 368 L CB 10 270 543 36 368 L CG 9 263 556 36 368 L CD1 5 248 554 37 368 L CD2 22 263 563 37 369 I N 13 302 528 31 369 I CA 16 308 516 28 369 I C 27 319 518 29 369 I O 25 329 526 29 369 I CB 4 314 509 26 369 I CG1 -5 303 505 22 369 I CG2 8 323 497 21 369 I CD1 -18 308 499 21 370 T N 38 318 511 27 370 T CA 49 328 511 28 370 T C 48 337 499 27 370 T O 50 332 488 30 370 T CB 63 322 512 29 370 T OG1 64 314 525 27 370 T CG2 74 332 512 24 371 S N 45 350 501 31 371 S CA 45 360 490 32 371 S C 52 372 496 34 371 S O 50 376 507 30 371 S CB 30 364 487 34 371 S OG 23 369 499 33 372 C N 62 377 488 34 372 C CA 70 388 491 35 372 C C 80 384 503 33 372 C O 84 392 511 31 372 C CB 62 400 496 35 372 C SG 55 410 482 34 373 S N 84 371 502 33 373 S CA 93 365 512 35 373 S C 86 364 527 35 373 S O 93 361 536 35 373 S CB 106 372 513 34 373 S OG 114 370 501 33 374 S N 73 367 527 30 374 S CA 66 368 540 27 374 S C 55 358 540 27 374 S O 53 350 530 26 374 S CB 61 382 541 28 374 S OG 71 392 539 36 375 N N 47 358 551 26 375 N CA 36 349 553 24 375 N C 28 355 565 26 375 N O 33 363 573 25 375 N CB 40 334 556 25 375 N CG 46 332 569 28 375 N OD1 59 333 571 24 375 N ND2 39 328 579 27 376 V N 15 351 566 26 376 V CA 6 355 576 24 376 V C 8 345 588 23 376 V O 10 334 585 22 376 V CB -8 356 571 27 376 V CG1 -18 356 583 22 376 V CG2 -11 368 562 23 377 S N 7 351 600 23 377 S CA 8 342 612 21 377 S C 0 348 623 21 377 S O -5 359 621 21 377 S CB 23 341 617 15 377 S OG 25 328 624 17 378 V N -2 341 634 25 378 V CA -11 345 645 27 378 V C -4 346 659 24 378 V O 4 338 662 23 378 V CB -23 335 646 25 378 V CG1 -35 341 654 26 378 V CG2 -27 330 633 28 379 A N -8 356 666 25 379 A CA -3 359 680 26 379 A C -16 363 687 29 379 A O -27 361 682 29 379 A CB 6 370 680 22 380 H N -14 369 699 29 380 H CA -26 373 707 27 380 H C -22 386 714 28 380 H O -11 387 720 31 380 H CB -29 363 718 28 380 H CG -33 350 712 30 380 H ND1 -46 345 711 30 380 H CD2 -25 339 708 30 380 H CE1 -46 333 706 31 380 H NE2 -33 329 704 34 381 D N -30 396 713 27 381 D CA -27 409 720 29 381 D C -29 409 735 31 381 D O -32 398 740 32 381 D CB -36 420 714 32 381 D CG -51 419 717 37 381 D CD1 -55 409 722 31 381 D OD2 -58 429 714 43 382 A N -28 420 742 34 382 A CA -30 421 756 37 382 A C -43 413 760 38 382 A O -42 404 768 40 382 A CB -31 435 760 35 383 S N -54 417 754 38 383 S CA -67 411 757 39 383 S C -69 396 753 39 383 S O -80 391 755 44 383 S CB -78 419 750 36 383 S OG -77 432 753 40 384 G N -59 389 748 37 384 G CA -61 375 745 32 384 G C -66 373 731 32 384 G O -66 361 726 34 385 K N -71 383 724 33 385 K CA -77 382 711 35 385 K C -67 377 701 36 385 K O -55 381 701 36 385 K CB -83 395 706 34 385 K CG -88 395 692 38 385 K CD -95 409 687 37 385 K CE -85 421 689 38 385 K NZ -92 433 685 36 386 R N -71 369 692 37 386 R CA -62 364 681 39 386 R C -60 375 671 39 386 R O -69 381 666 40 386 R CB -68 352 674 38 386 R CG -67 339 682 43 386 R CD -75 327 676 45 386 R NE -73 326 661 47 386 R CZ -64 318 655 46 386 R NH1 -56 310 663 44 386 R NH2 -63 318 642 46 387 V N -47 377 668 38 387 V CA -43 388 658 37 387 V C -34 383 647 35 387 V O -25 375 650 36 387 V CB -38 401 666 36 387 V CG1 -28 397 676 37 387 V CG2 -32 411 656 38 388 Y N -36 386 635 34 388 Y CA -28 382 624 30 388 Y C -18 393 621 29 388 Y O -21 405 622 31 388 Y CB -36 380 611 29 388 Y CG -47 369 612 23 388 Y CD1 -44 356 611 23 388 Y CD2 -60 372 617 26 388 Y CE1 -53 346 613 32 388 Y CE2 -69 362 619 30 388 Y CZ -66 349 617 32 388 Y OH -75 339 620 39 389 Y N -6 389 617 28 389 Y CA 4 398 615 23 389 Y C 14 392 604 20 389 Y O 14 380 601 18 389 Y CB 12 401 628 20 389 Y CG 20 390 633 19 389 Y CD1 14 379 640 18 389 Y CD2 34 389 631 20 389 Y CE1 21 368 644 15 389 Y CE2 41 378 635 14 389 Y CZ 34 367 641 14 389 Y OH 41 356 644 18 390 L N 22 400 598 22 390 L CA 32 396 588 20 390 L C 46 392 594 21

390 L O 52 400 601 19 390 L CB 33 407 578 21 390 L CG 39 404 564 21 390 L CD1 29 394 557 20 390 L CD2 40 416 556 23 391 T N 51 381 589 18 391 T CA 64 376 594 19 391 T C 71 370 582 21 391 T O 66 371 571 23 391 T CB 62 366 606 18 391 T OG1 76 363 610 20 391 T CG2 55 353 601 15 392 R N 83 365 584 20 392 R CA 91 358 574 20 392 R C 102 350 581 22 392 R O 105 352 593 24 392 R CB 98 369 565 21 392 R CG 107 379 573 18 392 R CD 117 385 563 18 392 R NE 126 375 557 19 392 R CZ 131 377 545 16 392 R NH1 130 388 539 20 392 R NH2 138 367 540 13 393 D N 109 342 574 20 393 D CA 120 334 579 24 393 D C 131 345 582 25 393 D O 134 353 574 26 393 D CB 125 325 568 25 393 D CG 136 315 573 25 393 D OD1 147 320 574 28 393 D OD2 134 303 574 27 394 P N 137 344 594 25 394 P CA 147 355 597 24 394 P C 162 353 593 21 394 P O 170 360 597 19 394 P CB 145 356 613 21 394 P CG 143 342 617 22 394 P CD 135 335 606 21 395 T N 164 342 585 22 395 T CA 178 339 581 20 395 T C 185 351 574 21 395 T O 196 354 578 22 395 T CB 179 327 572 20 395 T OG1 173 315 580 24 395 T CG2 193 323 568 19 396 T N 179 356 563 18 396 T CA 185 367 556 20 396 T C 186 380 565 19 396 T O 196 386 565 17 396 T CB 179 369 542 20 396 T OG1 180 358 534 20 396 T CG2 186 381 535 16 397 P N 175 383 572 18 397 P CA 176 395 581 17 397 P C 187 394 591 16 397 P O 194 404 594 18 397 P CB 162 395 587 19 397 P CG 153 391 576 14 397 P CD 161 379 571 17 398 L N 189 382 597 18 398 L CA 199 380 607 20 398 L C 213 380 601 20 398 L O 223 385 607 20 398 L CB 196 367 615 20 398 L CG 184 368 625 19 398 L CD1 182 354 631 19 398 L CD2 186 378 635 20 399 A N 215 373 589 19 399 A CA 228 373 583 16 399 A C 233 387 580 15 399 A O 244 390 581 14 399 A CB 227 365 570 16 400 R N 223 396 575 15 400 R CA 227 410 572 15 400 R C 229 418 585 16 400 R O 237 428 584 14 400 R CB 215 417 564 14 400 R CG 212 408 552 17 400 R CD 203 415 541 19 400 R NE 205 407 529 22 400 R CZ 199 410 517 22 400 R NH1 190 420 516 26 400 R NH2 201 402 507 21 401 A N 222 415 596 19 401 A CA 224 422 608 19 401 A C 239 419 613 18 401 A O 246 428 618 19 401 A CB 215 417 619 17 402 A N 243 406 611 18 402 A CA 257 403 615 18 402 A C 267 411 607 20 402 A O 276 417 613 20 402 A CB 260 388 612 15 403 W N 264 413 594 15 403 W CA 273 421 586 19 403 W C 274 435 590 19 403 W O 284 441 591 17 403 W CB 269 420 571 19 403 W CG 280 425 561 20 403 W CD1 283 438 559 19 403 W CD2 289 417 553 19 403 W NE1 294 439 550 19 403 W CE2 297 426 546 19 403 W CE3 290 403 551 19 403 W CZ2 307 421 537 21 403 W CZ3 300 398 543 23 403 W CH2 308 407 536 17 404 E N 262 441 593 20 404 E CA 260 455 597 18 404 E C 265 458 611 17 404 E O 268 469 615 20 404 E CB 246 460 595 19 404 E CG 242 461 581 18 404 E CD 227 460 578 26 404 E OE1 219 459 587 25 404 E OE2 223 461 566 23 405 T N 267 447 619 19 405 T CA 273 448 633 22 405 T C 287 453 632 23 405 T O 291 462 639 27 405 T CB 272 435 640 21 405 T OG1 258 432 643 20 405 T CG2 279 435 654 17 406 A N 295 448 622 22 406 A CA 309 451 621 23 406 A C 313 461 609 25 406 A O 324 465 608 25 406 A CB 317 438 619 22 407 R N 303 464 601 26 407 R CA 306 473 589 25 407 R C 294 483 587 25 407 R O 283 479 588 30 407 R CB 306 465 576 26 407 R CG 319 458 573 27 407 R CD 329 469 568 32 407 R NE 342 463 565 34 407 R CZ 351 458 573 38 407 R NH1 349 459 586 36 407 R NH2 361 451 568 36 408 H N 298 495 584 29 408 H CA 287 505 582 34 408 H C 283 503 567 34 408 H O 292 502 559 37 408 H CB 293 519 585 38 408 H CG 295 522 599 46 408 H ND1 307 527 604 49 408 H CD2 287 520 610 48 408 H CE1 306 528 617 51 408 H NE2 294 524 621 50 409 T N 270 502 565 33 409 T CA 265 501 551 29 409 T C 257 513 547 26 409 T O 253 521 555 24 409 T CB 257 487 550 25 409 T OG1 247 487 560 27 409 T CG2 267 475 550 24 410 P N 255 514 533 29 410 P CA 247 525 528 27 410 P C 232 523 531 25 410 P O 224 533 532 27 410 P CB 250 525 513 28 410 P CG 262 517 512 30 410 P CD 261 506 522 32 411 V N 228 511 533 26 411 V CA 214 508 536 29 411 V C 214 498 548 27 411 V O 220 487 548 30 411 V CB 207 501 525 31 411 V CG1 192 498 529 28 411 V CG2 207 510 512 31 412 N N 208 503 559 26 412 N CA 207 495 572 21 412 N C 195 487 572 18 412 N O 184 491 575 22 412 N CB 206 505 584 18 412 N CG 219 513 585 18 412 N OD1 228 509 591 24 412 N ND2 219 525 578 21 413 S N 197 474 568 18 413 S CA 186 465 567 22 413 S C 179 462 581 23 413 S O 167 459 581 22 413 S CB 189 451 560 20 413 S OG 198 443 568 23 414 W N 187 462 592 21 414 W CA 182 459 605 18 414 W C 171 470 609 18 414 W O 161 466 615 20 414 W CB 193 459 615 16 414 W CG 200 473 618 16 414 W CD1 212 477 612 15 414 W CD2 196 483 627 18 414 W NE1 215 490 617 17 414 W CE2 205 494 626 19 414 W CE3 185 485 635 20 414 W CZ2 204 506 633 17 414 W CZ3 183 497 642 19 414 W CH2 193 507 641 21 415 L N 173 482 605 15 415 L CA 163 492 608 18 415 L C 151 491 599 21 415 L O 140 493 604 22 415 L CB 169 506 606 16 415 L CG 161 519 608 18 415 L CD1 154 519 621 18 415 L CD2 170 531 607 16 416 G N 153 487 586 21 416 G CA 141 485 577 16 416 G C 133 473 583 18 416 G O 121 473 583 18 417 N N 140 463 587 16 417 N CA 134 451 592 19 417 N C 127 453 606 21 417 N O 116 447 608 21 417 N CB 144 440 594 17 417 N CG 146 432 580 23 417 N OD1 137 432 572 23 417 N ND2 158 427 578 20 418 I N 132 462 614 18 418 I CA 125 464 627 21 418 I C 112 472 623 23 418 I O 101 468 628 23 418 I CB 133 473 636 23 418 I CG1 144 465 643 20 418 I CG2 125 480 647 22 418 I CD1 154 474 652 19 419 I N 112 481 614 20 419 I CA 100 489 610 23 419 I C 90 480 604 23 419 I O 78 480 608 23 419 I CB 104 501 600 20 419 I CG1 112 511 608 17 419 I CG2 91 507 595 18 419 I CD1 118 522 599 19 420 M N 94 472 594 21 420 M CA 84 464 587 21 420 M C 79 452 595 21 420 M O 68 448 593 18 420 M CB 91 459 574 22 420 M CG 94 471 564 25 420 M SD 77 481 559 35 420 M CE 70 467 545 28 421 Y N 88 446 603 21 421 Y CA 84 434 610 17 421 Y C 84 436 626 17 421 Y O 86 427 633 19 421 Y CB 94 422 607 16 421 Y CG 93 418 592 19 421 Y CD1 83 410 588 17 421 Y CD2 102 422 583 20 421 Y CE1 82 406 575 24 421 Y CE2 102 419 570 20 421 Y CZ 91 410 566 26 421 Y OH 90 407 552 24 422 A N 81 448 630 17 422 A CA 80 451 644 20 422 A C 72 441 653 24 422 A O 76 438 664 29 422 A CB 75 465 646 14 423 P N 61 436 648 25 423 P CA 53 426 656 23 423 P C 59 412 657 22 423 P O 54 404 666 22 423 P CB 39 426 648 24 423 P CG 38 439 642 23 423 P CD 52 441 636 21 424 T N 69 409 649 20 424 T CA 75 396 650 20 424 T C 83 392 662 21 424 T O 89 401 668 23 424 T CB 83 392 637 22 424 T OG1 95 401 637 22 424 T CG2 75 394 624 16 425 L N 83 380 665 21 425 L CA 91 374 677 22 425 L C 106 377 675 22 425 L O 112 384 684 18 425 L CB 88 359 677 22 425 L CG 93 349 687 30 425 L CD1 87 352 701 31 425 L CD2 88 335 683 28 426 W N 111 375 663 22 426 W CA 125 377 660 19 426 W C 130 391 659 20 426 W O 141 395 664 20 426 W CB 129 368 647 22 426 W CG 120 372 635 25 426 W CD1 108 366 631 25 426 W CD2 123 382 625 23 426 W NE1 103 372 620 20 426 W CE2 112 382 616 24 426 W CE3 133 392 624 19 426 W CZ2 111 391 605 21 426 W CZ3 133 400 613 19 426 W CH2 122 400 604 24 427 A N 122 400 654 16 427 A CA 126 414 653 16 427 A C 125 421 667 18 427 A O 133 430 669 18 427 A CB 117 422 643 19 428 R N 116 417 675 19 428 R CA 115 422 689 19 428 R C 126 418 698 15 428 R O 133 426 704 17 428 R CB 101 419 694 13 428 R CG 90 427 688 17 428 R CD 76 422 692 21 428 R NE 71 428 704 24 428 R CZ 63 423 713 26 428 R NH1 58 411 710 20 428 R NH2 59 429 724 20 429 M N 128 405 699 18 429 M CA 138 399 708 20 429 M C 152 400 704 20 429 M O 161 401 712 23 429 M CB 134 385 711 17 429 M CG 120 383 717 23 429 M SD 115 365 723 29 429 M CE 99 369 734 39 430 I N 155 398 691 19 430 I CA 169 399 686 18 430 I C 173 412 680 18 430 I O 182 419 685 16 430 I CB 172 387 677 18 430 I CG1 168 374 684 17 430 I CG2 187 387 673 15 430 I CD1 169 362 675 20 431 L N 167 416 669 18 431 L CA 170 429 663 16 431 L C 170 441 672 18 431 L O 181 448 673 16 431 L CB 162 431 650 16 431 L CG 164 422 638 17 431 L CD1 156 427 626 12 431 L CD2 179 420 635 16 432 M N 159 444 678 16 432 M CA 158 455 687 17 432 M C 168 455 699 14 432 M O 174 465 702 17 432 M CB 144 457 692 19 432 M CG 133 459 682 24 432 M SD 115 462 690 25 432 M CE 116 451 707 40 433 T N 168 443 705 16 433 T CA 178 442 717 16 433 T C 192 444 712 17 433 T O 199 453 718 19 433 T CB 176 428 722 19 433 T OG1 162 425 725 22 433 T CG2 184 426 735 17 434 H N 197 437 702 16 434 H CA 210 438 698 18 434 H C 214 453 694 17 434 H O 223 459 699 18 434 H CB 213 429 686 20 434 H CG 227 429 680 24 434 H ND1 237 423 687 24 434 H CD2 232 433 669 20 434 H CE1 248 424 680 26 434 H NE2 245 430 668 22 435 F N 207 458 684 19 435 F CA 211 471 679 14 435 F C 208 483 689 17 435 F O 216 492 688 14 435 F CB 204 474 665 16 435 F CG 210 466 654 16 435 F CD1 223 469 649 14 435 F CD2 204 454 649 15 435 F CE1 229 461 640 16 435 F CE2 210 446 640 15 435 F CZ 223 449 635 12 436 F N 198 482 697 19 436 F CA 196 493 707 18 436 F C 208 492 717 16 436 F O 212 502 722 17 436 F CB 182 493 713 16 436 F CG 173 502 706 15 436 F CD1 165 497 696 16 436 F CD2 171 515 710 15 436 F CE1 156 506 689 11 436 F CE2 163 524 704 16 436 F CZ 155 519 693 10 437 S N 214 480 719 18 437 S CA 225 478 728 21 437 S C 237 486 722 20 437 S O 243 495 729 20 437 S CB 229 464 729 17 437 S OG 239 461 739 22 438 I N 240 484 709 23 438 I CA 251 491 702 23 438 I C 249 506 701 23 438 I O 258 514 703 27 438 I CB 253 486 688 22 438 I CG1 257 471 687 19 438 I CG2 264 494 681 29 438 I CD1 255 465 674 17 439 L N 237 510 698 23 439 L CA 234 525 697 24 439 L C 236 532 710 24 439 L O 240 544 710 23 439 L CB 220 527 692 28 439 L CG 215 522 679 31 439 L CD1 200 524 677 27 439 L CD2 223 529 667 25 440 L N 233 526 722 23 440 L CA 234 531 735 23 440 L C 249 534 738 21 440 L O 252 545 742 21 440 L CB 229 521 745 23 440 L CG 214 522 750 20 440 L CD1 210 510 756 23 440 L CD2 213 534 758 21 441 A N 257 524 736 23 441 A CA 271 524 739 25 441 A C 279 535 731 27 441 A O 288 541 737 31 441 A CB 278 510 735 23 442 Q N 274 538 719 26 442 Q CA 280 549 711 27 442 Q C 273 562 712 30 442 Q O 277 572 705 30 442 Q CB 281 544 696 27 442 Q CG 286 530 694 22 442 Q CD 300 529 700 26 442 Q OE1 308 539 701 28 442 Q NE2 304 517 703 23 443 E N 262 562 720 35 443 E CA 254 574 721 37 443 E C 249 579 708 35 443 E O 250 591 705 35 443 E CB 261 585 729 42 443 E CG 259 583 745 52 443 E CD 269 591 753 58 443 E OE1 269 604 751 62 443 E OE2 276 586 762 60 444 Q N 244 570 699 33 444 Q CA 239 573 686 33 444 Q C 224 570 684 35 444 Q O 220 567 672 38 444 Q CB 248 566 676 35 444 Q CG 262 573 674 33 444 Q CD 271 565 665 38 444 Q OE1 268 553 661 35 444 Q NE2 283 570 663 34 445 L N 216 571 694 31 445 L CA 202 569 693 31 445 L C 195 580 684 30 445 L O 185 577 678 31 445 L CB 196 569 706 32 445 L CG 189 556 711 33 445 L CD1 197 543 708 28 445 L CD2 187 557 726 36 446 E N 201 592 684 28 446 E CA 195 603 676 31 446 E C 202 605 663 29 446 E O 199 615 656 28 446 E CB 195 616 684 39 446 E CG 203 615 698 51 446 E CD 218 616 696 56 446 E OE1 224 606 692 53 446 E OE2 224 626 700 60 447 K N 210 596 659 28 447 K CA 217 597 646 29 447 K C 208 591 635 26 447 K O 205 579 635 25 447 K CB 230 589 647 28 447 K CG 240 592 635 32 447 K CD 250 581 635 34 447 K CE 259 583 623 36 447 K NZ 268 571 622 42 448 A N 204 599 625 24 448 A CA 195 594 614 24 448 A C 203 584 606 23 448 A O 215 586 603 25 448 A CB 191 606 606 22 449 L N 197 573 603 24 449 L CA 203 562 595 26 449 L C 194 560 583 27 449 L O 182 561 583 28 449 L CB 204 549 603 24 449 L CG 214 548 614 21 449 L CD1 213 534 620 17 449 L CD2 228 550 609 21 450 D N 201 556 571 26 450 D CA 193 553 559 25 450 D C 189 539 559 23 450 D O 196 530 561 22 450 D CB 202 556 546 29 450 D CG 205 570 544 30 450 D OD1 196 579 547 32 450 D OD2 216 573 539 34 451 C N 176 537 555 23 451 C CA 170 524 554 24 451 C C 161 524 542 22 451 C O 159 535 536 21 451 C CB 162 520 566 28 451 C SG 149 531 571 30 452 Q N 156 513 538 22 452 Q CA 147 513 526 24 452 Q C 133 506 529 22 452 Q O 133 496 536 20 452 Q CB 154 506 514 22 452 Q CG 165 515 509 30 452 Q CD 170 511 496 36 452 Q OE1 169 499 492 35 452 Q NE2 176 521 488 34 453 I N 123 512 524 22 453 I CA 109 506 525 21 453 I C 103 506 511 19 453 I O 101 517 505 19 453 I CB 101 516 534 21 453 I CG1 107 515 549 20 453 I CG2 86 512 534 22 453 I CD1 103 527 557 22 454 Y N 100 494 506 22 454 Y CA 95 492 492 25 454 Y C 103 499 482 26 454 Y O 99 505 472 24 454 Y CB 80 497 491 24 454 Y CG 69 489 498 21 454 Y CD1 72 476 502 20 454 Y CD2 57 494 501 22 454 Y CE1 62 468 509 28 454 Y CE2 47 487 508 23 454 Y CZ 50 474 512 27 454 Y OH 40 467 519 25 455 G N 117 497 484 26 455 G CA 126 503 474 20 455 G C 130 517 476 18 455 G O 140 522 470 24 456 A N 122 525 483 19 456 A CA 125 539 485 18 456 A C 134 541 497 20 456 A O 133 534 507 16 456 A CB 112 548 486 17 457 C N 143 551 497 19 457 C CA 152 554 507 23 457 C C 147 564 517 20 457 C O 143 576 513 20 457 C CB 166 557 502 26 457 C SG 178 560 516 39 458 Y N 148 561 530 22 458 Y CA 144 570 541 19 458 Y C 155 571 551 20 458 Y O 162 562 554 21 458 Y CB 131 564 548 20 458 Y CG 119 563 539 20 458 Y CD1 117 552 532 21 458 Y CD2 110 574 539 20 458 Y CE1 105 550 524 24 458 Y CE2 99 573 531 25 458 Y CZ 96 561 523 27 458 Y OH 85 560 515 34 459 S N 156 583 556 20 459 S CA 166 586 567 22 459 S C 157 587 579 23 459 S O 149 595 580 24 459 S CB 173 600 564 20 459 S OG 182 603 574 30 460 I N 160 578 589 21 460 I CA 152 577 601 23 460 I C 161 576 614 24 460 I O 171 569 614 24 460 I CB 143 564 600 21 460 I CG1 132 567 590 19 460 I CG2 137 561 614 18 460 I CD1 124 555 586 16 461 E N 157 584 624 24 461 E CA 163 584 637 26 461 E C 158 572 645 25 461 E O 146 571 647 23 461 E CB 161 596 645 27 461 E CG 164 609 638 32 461 E CD 166 621 648 35 461 E OE1 162 620 660 38 461 E OE2 173 631 644 39 462 P N 167 563

651 24 462 P CA 162 552 659 24 462 P C 153 555 671 25 462 P O 144 547 674 22 462 P CB 175 545 663 20 462 P CG 184 547 651 17 462 P CD 181 562 648 19 463 L N 154 567 676 25 463 L CA 146 572 687 28 463 L C 131 573 683 30 463 L O 122 573 692 30 463 L CB 151 585 693 27 463 L CG 163 586 702 31 463 L CD1 166 600 707 31 463 L CD2 162 577 714 27 464 D N 129 574 670 30 464 D CA 115 576 665 26 464 D C 107 563 663 25 464 D O 95 563 660 24 464 D CB 115 583 652 27 464 D CG 117 598 653 27 464 D OD1 111 604 662 29 464 D OD2 125 604 645 35 465 L N 114 551 665 21 465 L CA 108 538 663 21 465 L C 95 536 670 24 465 L O 86 530 665 25 465 L CB 118 527 665 20 465 L CG 129 525 654 25 465 L CD1 140 516 659 18 465 L CD2 122 520 642 22 466 P N 94 540 683 26 466 P CA 81 538 691 25 466 P C 69 544 683 23 466 P O 59 537 681 23 466 P CB 84 545 704 24 466 P CG 98 543 706 25 466 P CD 104 546 692 26 467 Q N 70 556 679 22 467 Q CA 60 563 672 26 467 Q C 57 557 658 29 467 Q O 46 554 654 29 467 Q CB 63 578 670 26 467 Q CG 64 585 683 39 467 Q CD 79 590 685 45 467 Q OE1 81 602 682 51 467 Q NE2 88 581 689 44 468 I N 68 554 650 27 468 I CA 67 548 637 25 468 I C 59 535 638 26 468 I O 50 532 630 29 468 I CB 81 546 630 22 468 I CG1 88 559 628 21 468 I CG2 79 539 617 18 468 I CD1 102 558 624 20 469 I N 63 527 648 23 469 I CA 57 514 650 21 469 I C 42 515 653 23 469 I O 34 508 648 22 469 I CB 64 505 660 22 469 I CG1 78 502 655 20 469 I CG2 57 492 662 21 469 I CD1 87 494 664 18 470 E N 38 524 662 25 470 E CA 25 526 666 28 470 E C 16 530 654 26 470 E O 5 525 652 28 470 E CB 23 537 677 29 470 E CG 9 538 683 31 470 E CD 6 551 691 32 470 E OE1 15 556 698 28 470 E OE2 -5 555 691 31 471 R N 21 540 647 27 471 R CA 14 545 635 27 471 R C 11 534 624 28 471 R O 1 535 617 30 471 R CB 21 557 629 25 471 R CG 21 570 637 30 471 R CD 8 577 635 32 471 R NE 4 579 621 33 471 R CZ 7 589 614 34 471 R NH1 14 600 619 32 471 R NH2 4 590 601 36 472 L N 21 525 622 28 472 L CA 19 515 612 26 472 L C 13 501 617 27 472 L O 7 494 609 28 472 L CB 33 510 607 25 472 L CG 44 520 603 26 472 L CD1 54 512 595 25 472 L CD2 39 532 595 26 473 H N 16 498 629 27 473 H CA 11 485 635 25 473 H C 2 486 646 25 473 H O -4 477 650 24 473 H CB 23 476 639 23 473 H CG 33 474 628 22 473 H ND1 32 464 619 21 473 H CD2 45 480 626 21 473 H CE1 43 464 611 20 473 H NE2 51 474 615 19 474 G N 1 498 652 25 474 G CA -7 501 663 29 474 G C 0 497 676 32 474 G O 10 491 676 32 475 L N -7 499 687 32 475 L CA -1 496 700 27 475 L C 0 481 703 25 475 L O 9 477 711 26 475 L CB -9 502 712 26 475 L CG -8 517 713 25 475 L CD1 -18 522 723 28 475 L CD2 6 520 717 27 476 S N -7 472 696 24 476 S CA -6 458 698 25 476 S C 7 452 694 28 476 S O 11 442 699 29 476 S CB -17 450 690 25 476 S OG -15 453 676 30 477 A N 14 460 686 28 477 A CA 28 456 682 26 477 A C 37 455 694 25 477 A O 47 447 694 28 477 A CB 33 465 672 24 478 F N 34 463 705 23 478 F CA 42 463 717 25 478 F C 37 452 727 27 478 F O 43 450 737 30 478 F CB 41 476 723 20 478 F CG 45 488 714 23 478 F CD1 57 486 706 20 478 F CD2 38 499 713 19 478 F CE1 61 496 698 15 478 F CE2 42 510 705 19 478 F CZ 54 508 697 14 479 S N 26 445 724 28 479 S CA 20 435 733 28 479 S C 17 421 729 26 479 S O 11 413 736 25 479 S CB 7 441 740 29 479 S OG 3 453 734 35 480 L N 21 418 717 26 480 L CA 18 405 712 26 480 L C 25 394 719 26 480 L O 36 395 724 28 480 L CB 20 403 697 27 480 L CG 13 413 688 28 480 L CD1 16 410 673 26 480 L CD2 -1 412 690 28 481 H N 18 382 721 24 481 H CA 23 371 728 27 481 H C 17 358 723 27 481 H O 8 359 714 27 481 H CB 21 372 743 27 481 H CG 7 372 747 26 481 H ND1 0 361 751 25 481 H CD2 -1 383 749 27 481 H CE1 -12 364 754 21 481 H NE2 -13 377 753 22 482 S N 21 347 728 30 482 S CA 15 334 724 31 482 S C 16 333 709 33 482 S O 5 333 702 33 482 S CB 1 332 730 33 482 S OG 1 331 744 34 483 Y N 28 332 704 31 483 Y CA 30 331 690 26 483 Y C 28 316 686 27 483 Y O 29 308 695 28 483 Y CB 45 335 687 24 483 Y CG 47 350 687 20 483 Y CD1 45 358 676 18 483 Y CD2 52 356 699 16 483 Y CE1 47 371 676 15 483 Y CE2 54 370 699 16 483 Y CZ 51 377 688 15 483 Y OH 54 390 688 16 484 S N 25 314 674 26 484 S CA 22 300 669 28 484 S C 34 291 670 29 484 S O 45 296 668 32 484 S CB 16 300 655 29 484 S OG 26 302 645 28 485 P N 33 278 673 29 485 P CA 43 268 674 29 485 P C 52 268 661 29 485 P O 64 267 662 28 485 P CB 36 255 676 28 485 P CG 24 259 684 32 485 P CD 20 272 677 31 486 G N 45 270 650 29 486 G CA 52 270 637 26 486 G C 61 281 636 25 486 G O 73 279 632 28 487 E N 57 293 640 22 487 E CA 66 305 640 23 487 E C 78 303 650 26 487 E O 89 305 646 25 487 E CB 57 317 644 20 487 E CG 64 331 643 25 487 E CD 72 334 629 23 487 E OE1 70 326 619 23 487 E OE2 79 343 628 22 488 I N 75 299 662 26 488 I CA 85 297 672 25 488 I C 95 287 667 26 488 I O 108 289 668 25 488 I CB 79 292 686 25 488 I CG1 70 303 691 26 488 I CG2 90 289 696 26 488 I CD1 62 299 703 26 489 N N 91 276 662 26 489 N CA 100 265 657 29 489 N C 109 270 645 31 489 N O 120 265 644 33 489 N CB 92 253 653 34 489 N CG 88 245 666 40 489 N OD1 95 243 675 43 489 N ND2 75 240 665 42 490 R N 104 279 637 30 490 R CA 111 284 626 28 490 R C 122 293 631 26 490 R O 134 292 626 23 490 R CB 103 291 615 24 490 R CG 111 297 603 25 490 R CD 103 301 591 20 490 R NE 94 312 595 22 490 R CZ 85 317 586 21 490 R NH1 83 312 574 26 490 R NH2 76 327 590 19 491 V N 119 302 640 26 491 V CA 129 312 645 25 491 V C 139 303 653 25 491 V O 151 304 649 24 491 V CB 122 322 655 25 491 V CG1 133 331 661 25 491 V CG2 112 331 647 23 492 A N 135 294 661 25 492 A CA 144 286 669 26 492 A C 154 278 660 28 492 A O 166 277 664 25 492 A CB 137 276 678 26 493 S N 149 272 649 28 493 S CA 158 264 640 28 493 S C 168 273 633 27 493 S O 180 270 631 27 493 S CB 150 256 630 30 493 S OG 142 246 637 44 494 C N 164 285 630 26 494 C CA 172 295 623 27 494 C C 184 299 632 27 494 C O 195 301 628 24 494 C CB 164 307 619 25 494 C SG 173 321 612 32 495 L N 181 301 645 26 495 L CA 192 305 655 25 495 L C 202 294 656 28 495 L O 214 297 656 30 495 L CB 186 309 668 23 495 L CG 175 319 669 23 495 L CD1 173 324 683 23 495 L CD2 178 331 659 21 496 R N 198 282 657 26 496 R CA 207 270 658 28 496 R C 216 269 645 27 496 R O 228 267 646 26 496 R CB 200 257 661 28 496 R CG 194 257 675 33 496 R CD 187 244 678 31 496 R NE 175 241 670 38 496 R CZ 163 242 674 41 496 R NH1 160 246 686 46 496 R NH2 153 240 665 40 497 K N 210 271 634 30 497 K CA 217 271 621 27 497 K C 228 281 619 26 497 K O 239 278 616 25 497 K CB 206 273 610 27 497 K CG 212 274 596 26 497 K CD 201 275 585 27 497 K CE 194 288 586 26 497 K NZ 184 290 575 27 498 L N 224 294 623 26 498 L CA 233 305 622 25 498 L C 243 306 634 25 498 L O 253 312 634 22 498 L CB 225 318 621 27 498 L CG 221 323 607 28 498 L CD1 217 313 597 29 498 L CD2 209 333 609 24 499 G N 239 299 645 25 499 G CA 247 300 657 23 499 G C 245 313 665 23 499 G O 254 320 670 22 500 V N 232 317 666 23 500 V CA 227 329 673 25 500 V C 223 324 686 25 500 V O 216 313 687 27 500 V CB 215 335 665 23 500 V CG1 210 347 673 20 500 V CG2 219 339 651 22 501 P N 226 331 697 26 501 P CA 221 327 711 28 501 P C 206 325 711 28 501 P O 198 332 705 30 501 P CB 226 339 719 24 501 P CG 238 344 712 23 501 P CD 233 344 698 25 502 P N 201 315 719 27 502 P CA 187 312 720 27 502 P C 179 323 725 26 502 P O 184 332 732 26 502 P CB 187 299 729 27 502 P CG 200 301 737 28 502 P CD 209 305 727 26 503 L N 166 324 722 26 503 L CA 157 334 727 25 503 L C 158 338 742 27 503 L O 156 350 745 27 503 L CB 143 332 722 25 503 L CG 140 332 707 22 503 L CD1 126 327 705 24 503 L CD2 141 347 702 17 504 R N 160 328 751 28 504 R CA 160 331 765 28 504 R C 172 341 768 27 504 R O 171 349 777 27 504 R CB 161 318 773 30 504 R CG 172 309 768 36 504 R CD 172 296 777 39 504 R NE 180 286 771 45 504 R CZ 193 286 771 47 504 R NH1 200 296 776 50 504 R NH2 200 276 765 48 505 V N 183 340 761 26 505 V CA 195 348 763 24 505 V C 191 363 759 24 505 V O 194 372 766 25 505 V CB 207 344 754 21 505 V CG1 218 354 755 14 505 V CG2 212 330 760 17 506 W N 183 364 748 22 506 W CA 179 377 743 20 506 W C 169 384 753 20 506 W O 170 396 755 20 506 W CB 173 376 729 20 506 W CG 183 373 719 14 506 W CD1 184 361 713 13 506 W CD2 193 381 714 13 506 W NE1 195 361 704 13 506 W CE2 201 374 705 14 506 W CE3 197 394 717 14 506 W CZ2 212 379 699 14 506 W CZ3 208 400 710 17 506 W CH2 216 392 701 10 507 R N 161 376 760 22 507 R CA 151 381 770 22 507 R C 159 387 782 21 507 R O 156 397 787 20 507 R CB 141 370 775 27 507 R CG 133 374 787 28 507 R CD 122 365 790 33 507 R NE 110 369 782 38 507 R CZ 105 362 772 35 507 R NH1 110 350 769 37 507 R NH2 94 367 766 35 508 H N 170 380 785 23 508 H CA 179 384 796 26 508 H C 185 397 792 24 508 H O 185 407 800 23 508 H CB 189 374 800 32 508 H CG 197 376 812 38 508 H ND1 196 368 823 44 508 H CD2 204 387 817 40 508 H CE1 202 373 834 44 508 H NE2 208 385 830 41 509 R N 191 398 780 22 509 R CA 197 410 775 19 509 R C 187 422 774 18 509 R O 191 433 776 16 509 R CB 204 408 762 21 509 R CG 215 397 762 20 509 R CD 222 397 749 22 509 R NE 234 387 749 22 509 R CZ 239 382 739 22 509 R NH1 235 385 727 26 509 R NH2 249 373 741 21 510 A N 175 419 770 19 510 A CA 165 429 768 18 510 A C 162 437 780 19 510 A O 159 449 780 22 510 A CB 152 423 762 17 511 R N 162 430 792 25 511 R CA 159 437 805 26 511 R C 170 447 808 24 511 R O 167 458 812 26 511 R CB 158 426 816 27 511 R CG 146 418 816 30 511 R CD 147 407 826 38 511 R NE 134 401 828 45 511 R CZ 132 388 830 51 511 R NH1 142 379 830 54 511 R NH2 119 383 831 49 512 S N 183 443 805 23 512 S CA 194 452 807 22 512 S C 193 464 797 20 512 S O 193 476 801 19 512 S CB 207 445 804 21 512 S OG 218 453 801 26 513 V N 191 461 784 21 513 V CA 190 472 774 20 513 V C 178 481 778 16 513 V O 179 493 776 21 513 V CB 187 466 759 22 513 V CG1 184 477 749 17 513 V CG2 199 458 754 23 514 R N 167 475 783 18 514 R CA 156 483 787 20 514 R C 158 492 798 18 514 R O 155 504 797 20 514 R CB 145 473 791 21 514 R CG 131 479 795 21 514 R CD 121 469 798 28 514 R NE 114 472 811 36 514 R CZ 107 483 813 37 514 R NH1 105 492 804 42 514 R NH2 102 485 825 41 515 A N 165 488 809 24 515 A CA 168 496 820 22 515 A C 178 507 816 22 515 A O 177 518 821 24 515 A CB 175 487 831 22 516 R N 187 504 807 24 516 R CA 196 514 802 27 516 R C 190 526 795 29 516 R O 194 537 797 30 516 R CB 206 507 793 28 516 R CG 220 505 799 29 516 R CD 224 490 799 24 516 R NE 229 485 786 29 516 R CZ 237 492 778 30 516 R NH1 242 504 781 32 516 R NH2 241 486 767 30 517 L N 179 522 787 30 517 L CA 172 532 780 27 517 L C 164 541 789 26 517 L O 164 554 788 24 517 L CB 162 526 770 26 517 L CG 169 519 758 23 517 L CD1 159 511 750 21 517 L CD2 175 530 749 23 518 L N 157 535 799 30 518 L CA 149 542 809 31 518 L C 158 552 817 32 518 L O 154 563 820 34 518 L CB 142 533 818 32 518 L CG 131 524 812 29 518 L CD1 127 513 820 30 518 L CD2 119 533 809 30 519 S N 171 549 819 35 519 S CA 181 557 826 36 519 S C 184 570 819 38 519 S O 189 579 825 38 519 S CB 193 549 829 36 519 S OG 191 537 837 41 520 Q N 182 570 806 39 520 Q CA 186 582 798 40 520 Q C 174 592 798 40 520 Q O 176 604 795 39 520 Q CB 188 578 783 42 520 Q CG 196 566 780 47 520 Q CD 211 568 783 52 520 Q OE1 217 578 778 52 520 Q NE2 217 558 790 52 521 G N 162 588 802 41 521 G CA 151 596 803 40 521 G C 147 600 789 43 521 G O 151 594 779 44 522 G N 139 611 788 44 522 G CA 134 616 775 42 522 G C 129 605 765 42 522 G O 122 596 769 43 523 R N 132 607 752 42 523 R CA 128 597 742 38 523 R C 135 584 743 36 523 R O 129 574 738 36 523 R CB 128 603 728 39 523 R CG 119 615 727 42 523 R CD 114 617 713 47 523 R NE 125 621 704 51 523 R CZ 127 616 692 51 523 R NH1 119 607 688 50 523 R NH2 137 620 685 48 524 A N 146 583 749 30 524 A CA 154 571 750 26 524 A C 145 562 760 24 524 A O 144 550 758 23 524 A CB 167 573 756 25 525 A N 139 568 770 26 525 A CA 131 561 780 27 525 A C 119 555 773 25 525 A O 115 544 776 25 525 A CB 127 570 791 28 526 T N 112 563 765 27 526 T CA 100 558 758 26 526 T C 103 546 749 23 526 T O 96 536 749 22 526 T CB 94 569 749 27 526 T OG1 94 581 756 32 526 T CG2 80 566 744 30 527 C N 115 545 743 23 527 C CA 120 534 735 22 527 C C 121 522 745 22 527 C O 117 511 741 22 527 C CB 133 536 729 24 527 C SG 134 546 714 25 528 G N 126 524 757 23 528 G CA 128 513 766 21 528 G C 114 508 771 21 528 G O 111 496 771 21 529 K N 105 518 774 25 529 K CA 92 515 779 28 529 K C 83 507 769 29 529 K O 76 497 772 29 529 K CB 85 527 784 28 529 K CG 70 525 788 33 529 K CD 64 539 792 37 529 K CE 49 537 794 40 529 K NZ 43 551 797 40 530 Y N 82 512 756 27 530 Y CA 74 506 746 25 530 Y C 80 494 738 21 530 Y O 73 484 737 20 530 Y CB 69 516 736 25 530 Y CG 59 526 741 25 530 Y CD1 62 536 749 30 530 Y CD2 45 524 738 26 530 Y CE1 53 545 755 29 530 Y CE2 36 533 743 29 530 Y CZ 40 543 752 31 530 Y OH 31 552 757 34 531 L N 92 496 734 23 531 L CA 99 485 726 21 531 L C 102 472 734 20 531 L O 102 462 729 19 531 L CB 111 490 719 17 531 L CG 110 503 711 20 531 L CD1 123 506 704 21 531 L CD2 99 502 701 19 532 F N 105 474 747 21 532 F CA 109 462 755 21 532 F C 99 459 767 26 532 F O 103 452 776 22 532 F CB 123 464 760 23 532 F CG 133 466 749 20 532 F CD1 139 455 743 18 532 F CD2 137 478 745 19 532 F CE1 147 456 732 17 532 F CE2 146 480 734 16 532 F CZ 151 469 728 8 533 N N 87 462 765 28 533 N CA 77 459 776 30 533 N C 75 444 777 28 533 N O 72 439 787 29 533 N CB 63 466 773 33 533 N CG 55 469 786 38 533 N OD1 46 462 789 40 533 N ND2 59 480 792 40 534 W N 78 437 765 26 534 W CA 77 422 765 23 534 W C 87 415 774 27 534 W O 85 403 777 27 534 W CB 79 417 750 24 534 W CG 92 421 744 23 534 W CD1 96 432 737 24 534 W CD2 105 414 745 20 534 W NE1 109 432 734 20 534 W CE2 115 421 739 21 534 W CE3 108 402 752 19 534 W CZ2 128 417 738 19 534 W CZ3 122 397 751 20 534 W CH2 131 405 744 17 535 A N 98 422 777 28 535 A CA

108 417 785 30 535 A C 106 415 800 32 535 A O 111 406 806 32 535 A CB 122 424 782 29 536 V N 99 425 806 35 536 V CA 96 425 820 39 536 V C 83 416 824 44 536 V O 75 414 815 43 536 V CB 94 439 826 40 536 V CG1 107 446 828 40 536 V CG2 85 447 817 33 537 K N 83 411 836 49 537 K CA 71 403 840 51 537 K C 59 411 843 53 537 K O 48 409 839 54 537 K CB 75 393 851 53 537 K CG 81 399 864 59 537 K CD 87 389 873 61 537 K CE 98 394 882 62 537 K NZ 106 384 888 61 538 T N 61 422 851 55 538 T CA 50 431 854 55 538 T C 51 442 844 54 538 T O 60 451 844 52 538 T CB 52 437 869 55 538 T OG1 53 427 878 51 538 T CG2 40 446 872 53 539 K N 43 441 834 53 539 K CA 42 450 822 53 539 K C 36 464 825 53 539 K O 27 465 834 54 539 K CB 33 443 811 53 539 K CG 34 428 810 51 539 K CD 46 424 801 50 539 K CE 47 409 799 52 539 K NZ 57 404 790 52 540 L N 41 474 818 50 540 L CA 36 487 820 49 540 L C 24 491 812 49 540 L O 19 483 804 49 540 L CB 47 498 817 46 540 L CG 59 501 827 47 540 L CD1 62 516 825 45 540 L CD2 55 498 841 48 541 K N 20 504 814 51 541 K CA 8 510 808 49 541 K C 6 509 793 48 541 K O -1 500 788 47 541 K CB 8 525 811 50 541 K CG 17 529 823 51 541 K CD 18 544 825 53 541 K CE 21 549 840 54 541 K NZ 9 548 849 48 542 L N 14 516 785 48 542 L CA 15 517 771 45 542 L C 2 523 765 43 542 L O -7 516 761 43 542 L CB 18 503 765 40 542 L CG 33 501 763 34 542 L CD1 41 506 775 31 542 L CD2 35 486 761 32 543 T N 2 536 765 42 543 T CA -8 544 760 43 543 T C -3 551 748 43 543 T O 8 550 744 42 543 T CB -12 554 771 42 543 T OG1 0 562 774 40 543 T CG2 -17 548 784 41 544 P N -13 556 740 43 544 P CA -8 563 728 44 544 P C 1 574 730 45 544 P O 0 583 739 45 544 P CB -22 568 722 44 544 P CG -31 557 726 43 544 P CD -27 554 740 42 545 I N 12 574 723 44 545 I CA 23 584 724 42 545 I C 18 596 716 45 545 I O 15 596 704 45 545 I CB 36 579 717 40 545 I CG1 40 565 723 35 545 I CG2 47 589 720 39 545 I CD1 51 559 715 36 546 P N 17 608 723 47 546 P CA 12 621 717 48 546 P C 19 626 705 51 546 P O 13 631 695 51 546 P CB 13 630 729 49 546 P CG 24 624 737 51 546 P CD 20 610 737 47 547 A N 33 625 704 52 547 A CA 40 629 693 51 547 A C 40 620 680 49 547 A O 47 623 670 49 547 A CB 55 632 697 52 548 A N 32 610 681 49 548 A CA 31 600 670 49 548 A C 23 606 658 51 548 A O 26 603 646 51 548 A CB 25 587 674 45 549 S N 12 613 661 54 549 S CA 4 619 651 55 549 S C 10 630 643 56 549 S O 6 633 632 59 549 S CB -8 624 657 52 549 S OG -6 634 667 52 550 Q N 21 636 648 55 550 Q CA 29 646 641 56 550 Q C 36 641 628 53 550 Q O 37 649 618 50 550 Q CB 39 653 650 60 550 Q CG 35 661 662 66 550 Q CD 46 667 670 70 550 Q OE1 56 659 673 69 550 Q NE2 45 679 674 72 551 L N 41 629 629 51 551 L CA 48 623 618 50 551 L C 41 623 605 50 551 L O 30 618 604 50 551 L CB 52 608 622 49 551 L CG 61 606 634 48 551 L CD1 62 591 637 43 551 L CD2 75 612 632 46 552 D N 48 628 594 48 552 D CA 42 628 581 49 552 D C 44 614 574 47 552 D O 54 612 567 48 552 D CB 48 639 573 50 552 D CG 41 642 560 52 552 D OD1 33 633 555 52 552 D OD2 44 652 554 54 553 L N 36 604 577 46 553 L CA 37 591 572 45 553 L C 31 589 558 46 553 L O 30 577 554 44 553 L CB 33 580 582 43 553 L CG 44 573 590 45 553 L CD1 53 583 596 40 553 L CD2 37 564 600 40 554 S N 26 599 552 47 554 S CA 19 598 539 50 554 S C 30 597 529 50 554 S O 41 603 530 54 554 S CB 10 610 536 50 554 S OG 18 622 535 49 555 G N 28 588 519 48 555 G CA 38 586 509 42 555 G C 46 574 512 39 555 G O 54 569 504 39 556 W N 44 568 524 35 556 W CA 52 557 529 37 556 W C 48 544 522 38 556 W O 56 536 517 39 556 W CB 51 555 544 35 556 W CG 62 561 551 35 556 W CD1 66 574 549 32 556 W CD2 70 556 561 33 556 W NE1 77 577 558 33 556 W CE2 79 566 566 34 556 W CE3 70 543 568 30 556 W CZ2 88 564 576 33 556 W CZ3 79 541 578 34 556 W CH2 88 551 582 35 557 F N 35 541 521 33 557 F CA 29 529 515 31 557 F C 20 533 504 30 557 F O 8 533 505 30 557 F CB 22 521 525 27 557 F CG 31 517 537 28 557 F CD1 42 508 535 25 557 F CD2 29 523 549 29 557 F CE1 50 505 545 25 557 F CE2 38 520 560 30 557 F CZ 48 511 558 28 558 V N 25 538 493 26 558 V CA 17 543 481 26 558 V C 22 535 469 26 558 V O 13 529 462 24 558 V CB 19 558 479 24 558 V CG1 11 562 467 29 558 V CG2 15 565 491 27 559 A N 35 535 467 24 559 A CA 40 528 455 24 559 A C 54 522 457 21 559 A O 60 525 467 24 559 A CB 40 537 443 26 560 G N 57 513 448 22 560 G CA 71 506 449 23 560 G C 80 514 441 24 560 G O 77 519 430 18 561 Y N 93 515 445 22 561 Y CA 103 522 438 18 561 Y C 117 514 437 20 561 Y O 127 521 435 22 561 Y CB 106 536 444 16 561 Y CG 94 545 445 20 561 Y CD1 89 551 433 19 561 Y CD2 86 546 457 20 561 Y CE1 78 559 434 17 561 Y CE2 75 554 457 23 561 Y CZ 71 561 446 23 561 Y OH 59 568 447 20 562 S N 116 501 438 22 562 S CA 128 493 438 23 562 S C 137 496 426 25 562 S O 132 495 414 25 562 S CB 125 478 438 23 562 S OG 136 470 440 31 563 G N 149 501 428 26 563 G CA 158 505 417 21 563 G C 155 519 411 22 563 G O 163 524 403 25 564 G N 145 525 416 16 564 G CA 141 538 411 15 564 G C 148 551 416 14 564 G O 143 562 413 16 565 D N 159 550 423 19 565 D CA 166 561 428 17 565 D C 158 572 435 18 565 D O 159 584 433 17 565 D CB 173 568 416 19 565 D CG 185 577 420 25 565 D OD1 192 574 430 26 565 D OD2 187 587 413 23 566 I N 149 567 444 21 566 I CA 140 576 452 21 566 I C 144 578 467 22 566 I O 148 568 474 20 566 I CB 125 571 451 18 566 I CG1 121 571 436 17 566 I CG2 116 579 460 15 566 I CD1 121 585 429 16 567 Y N 142 590 472 23 567 Y CA 146 593 486 27 567 Y C 135 602 493 35 567 Y O 129 611 486 34 567 Y CB 159 600 486 27 567 Y CG 163 606 500 28 567 Y CD1 170 598 510 32 567 Y CD2 161 620 503 27 567 Y CE1 173 604 522 33 567 Y CE2 165 625 515 31 567 Y CZ 171 617 525 35 567 Y OH 175 622 537 39 568 H N 134 601 506 40 568 H CA 124 609 514 43 568 H C 130 613 527 46 568 H O 138 605 533 44 568 H CB 111 602 515 40 568 H CG 103 601 503 42 568 H ND1 99 590 497 44 568 H CD2 98 611 495 40 568 H CE1 91 592 486 41 568 H NE2 90 605 485 41 569 S N 126 624 533 52 569 S CA 130 629 546 57 569 S C 145 632 546 60 569 S O 149 642 540 64 569 S CB 127 619 557 57 569 S OG 115 622 564 56 1001 X OW 165 413 548 8 1002 X OW 112 514 403 14 1003 X OW 136 486 313 13 1004 X OW 91 459 426 16 1005 X OW 57 632 371 17 1006 X OW 75 386 325 14 1007 X OW 23 397 463 18 1008 X OW 52 499 414 15 1009 X OW 252 550 342 17 1010 X OW 229 624 323 18 1011 X OW 160 565 378 18 1012 X OW 196 521 276 18 1013 X OW 33 447 296 18 1014 X OW 79 518 287 18 1015 X OW 212 489 291 17 1016 X OW 252 584 376 16 1017 X OW 113 500 325 24 1018 X OW 312 471 360 18 1019 X OW 81 456 711 16 1020 X OW 231 575 307 15 1021 X OW 97 482 449 19 1022 X OW -38 559 427 24 1023 X OW -95 504 265 19 1024 X OW 239 583 267 21 1025 X OW 81 523 391 17 1026 X OW 19 654 323 25 1027 X OW 180 612 403 29 1028 X OW 4 340 540 18 1029 X OW 91 415 219 24 1030 X OW 19 283 472 24 1031 X OW 307 451 398 19 1032 X OW 30 421 287 19 1033 X OW 270 617 443 22 1034 X OW 6 434 219 20 1035 X OW -7 537 426 18 1036 X OW 70 361 648 23 1037 X OW 7 451 616 31 1038 X OW 71 460 683 26 1039 X OW 14 474 596 24 1040 X OW 298 406 622 13 1041 X OW 58 525 411 19 1042 X OW 172 516 231 20 1043 X OW 48 425 603 17 1044 X OW 100 333 615 27 1045 X OW 145 396 380 26 1046 X OW 234 400 448 27 1047 X OW 135 450 244 25 1048 X OW 220 557 646 19 1049 X OW 377 446 646 18 1050 X OW 189 447 332 25 1051 X OW -18 648 396 35 1052 X OW 22 688 336 21 1053 X OW 71 455 740 21 1054 X OW 120 411 227 24 1055 X OW -69 335 215 24 1056 X OW 328 503 585 27 1057 X OW 101 337 546 23 1058 X OW -108 372 285 26 1059 X OW 228 432 519 27 1060 X OW -69 575 268 33 1061 X OW 257 562 318 25 1062 X OW 142 540 450 27 1063 X OW -84 536 269 31 1064 X OW 304 361 446 27 1065 X OW 11 258 262 28 1066 X OW 36 267 276 27 1067 X OW 284 341 452 26 1068 X OW 202 399 380 20 1069 X OW 135 415 550 20 1070 X OW -13 536 457 22 1071 X OW 85 508 314 23 1072 X OW -91 574 386 23 1073 X OW 11 405 192 21 1074 X OW 292 576 392 28 1075 X OW 141 614 166 31 1076 X OW 123 370 394 24 1077 X OW 271 573 350 36 1078 X OW -14 319 244 36 1079 X OW -62 463 539 25 1080 X OW -166 406 -146 6 1081 X OW -112 511 -1 14 1082 X OW -136 488 90 14 1083 X OW -92 455 -21 11 1084 X OW -55 629 27 14 1085 X OW -76 386 80 24 1086 X OW -28 381 -56 23 1087 X OW -52 494 -12 18 1088 X OW -252 552 58 19 1089 X OW -226 623 75 23 1090 X OW -158 564 21 12 1091 X OW -196 525 127 15 1092 X OW -35 445 109 19 1093 X OW -80 517 116 13 1094 X OW -214 491 112 18 1095 X OW -250 581 24 20 1096 X OW -111 498 78 16 1097 X OW -311 475 40 20 1098 X OW -80 446 -308 23 1099 X OW -232 576 92 16 1100 X OW -97 477 -47 20 1101 X OW 37 552 -24 15 1102 X OW 92 502 135 19 1103 X OW -237 586 135 29 1104 X OW -81 519 10 20 1105 X OW -19 651 73 19 1106 X OW -178 608 -7 17 1107 X OW -7 332 -135 16 1108 X OW -96 415 185 19 1109 X OW -23 278 -70 32 1110 X OW -307 457 3 21 1111 X OW -33 420 120 21 1112 X OW -273 611 -48 22 1113 X OW -12 431 186 19 1114 X OW 6 532 -25 18 1115 X OW -72 355 -244 16 1116 X OW -9 442 -213 24 1117 X OW -74 451 -280 28 1118 X OW -17 468 -193 27 1119 X OW -300 400 -222 17 1120 X OW -58 520 -10 24 1121 X OW -173 520 172 18 1122 X OW -50 419 -199 23 1123 X OW -103 327 -211 17 1124 X OW -148 396 23 25 1125 X OW -237 397 -46 22 1126 X OW -138 452 161 21 1127 X OW -220 553 -247 26 1128 X OW -376 445 -245 17 1129 X OW -189 450 71 19 1130 X OW 15 645 -1 24 1131 X OW -19 688 56 24 1132 X OW -71 444 -336 21 1133 X OW -125 414 175 23 1134 X OW 66 330 187 32 1135 X OW -315 495 -144 45 1136 X OW -106 330 -140 26 1137 X OW 103 369 122 30 1138 X OW -226 427 -118 23 1139 X OW 50 604 151 51 1140 X OW -255 563 83 23 1141 X OW -140 536 -50 20 1142 X OW 68 571 134 39 1143 X OW -303 365 -42 35 1144 X OW -17 253 146 36 1145 X OW -42 265 131 23 1146 X OW -290 344 -54 27 1147 X OW -206 397 21 19 1148 X OW -135 409 -145 22 1149 X OW 13 526 -54 27 1150 X OW -82 508 86 32 1151 X OW 89 570 14 23 1152 X OW -14 405 210 24 1153 X OW -289 572 12 33 1154 X OW -143 621 230 29 1155 X OW -129 368 11 34 1156 X OW -266 574 47 28 1157 X OW 3 319 162 36 1158 X OW 60 453 -137 21 1159 X OW -29 324 -245 26 1160 X OW 186 430 590 22 1161 X OW -186 423 -190 24 1162 X OW -51 306 -201 22 1163 X OW -27 295 -209 26 1164 X OW 74 331 547 25 1165 X OW 105 465 471 20 1166 X OW -157 291 -305 23 1167 X OW 21 429 604 25 1168 X OW -30 273 296 25 1169 X OW 155 296 708 20 1170 X OW 222 580 723 21 1171 X OW 200 291 693 25 1172 X OW -62 355 13 27 1173 X OW 133 479 502 21 1174 X OW -40 518 173 21 1175 X OW -215 573 -99 28 1176 X OW -111 165 440 49 1177 X OW -158 336 -146 28 1178 X OW 232 621 295 25 1179 X OW -306 459 -23 27 1180 X OW 14 517 -131 29 1181 X OW -163 355 -111 29 1182 X OW 155 346 549 25 1183 X OW -226 371 -45 27 1184 X OW -304 392 -312 31 1185 X OW 142 464 828 25 1186 X OW -161 501 -51 25 1187 X OW 143 582 390 29 1188 X OW -274 748 -6 28 1189 X OW -152 288 -339 23 1190 X OW 239 419 716 27 1191 X OW -32 518 683 28 1192 X OW -201 334 -124 25 1193 X OW -233 620 102 21 1194 X OW -326 342 -155 28 1195 X OW 372 430 750 52 1196 X OW -103 459 -68 28 1197 X OW 216 583 498 26 1198 X OW -354 354 -61 38 1199 X OW 104 163 52 29 1200 X OW 60 293 420 26 1201 X OW -177 277 -288 27 1202 X OW -128 556 221 32 1203 X OW -348 406 29 38 1204 X OW -269 371 166 29 1205 X OW -233 546 -169 32 1206 X OW -11 527 534 29 1207 X OW -241 439 -137 31 1208 X OW -58 454 236 29 1209 X OW -239 381 -438 27 1210 X OW 150 628 741 38 1211 X OW -96 256 406 26 1212 X OW 349 489 249 26 1213 X OW 110 418 851 26 1214 X OW 244 596 295 26 1215 X OW -140 453 -425 28 1216 X OW 28 440 -326 27 1217 X OW -160 537 210 25 1218 X OW -76 325 -141 30 1219 X OW 80 456 -91 32 1220 X OW 36 263 115 39 1221 X OW 194 731 277 25 1222 X OW 220 587 240 28 1223 X OW 128 412 393 30 1224 X OW -74 370 -345 40 1225 X OW -337 381 -277 33 1226 X OW 245 546 642 29 1227 X OW -100 660 -56 24 1228 X OW 113 707 214 32 1229 X OW -319 479 -37 29 1230 X OW -127 471 -101 28 1231 X OW -166 430 -136 43 1232 X OW 117 369 -315 40 1233 X OW -21 421 -197 27 1234 X OW -272 480 174 27 1235 X OW -51 348 -53 30 1236 X OW 175 526 439 25 1237 X OW -69 310 208 31 1238 X OW -75 312 159 29 1239 X OW -91 686 -65 31 1240 X OW -324 398 54 29 1241 X OW -174 524 -38 31 1242 X OW 152 299 743 25 1243 X OW -83 248 -210 26 1244 X OW -103 436 -3 23 1245 X OW -119 458 -141 37 1246 X OW -97 634 -184 31 1247 X OW -164 483 -148 25 1248 X OW 147 450 217 37 1249 X OW 86 375 52 26 1250 X OW -311 567 -302 31 1251 X OW 199 340 528 31 1252 X OW 39 294 492 34 1253 X OW 106 396 -78 25 1254 X OW 385 483 262 29 1255 X OW -228 759 -46 34 1256 X OW 60 615 -30 44 1257 X OW 164 489 552 27 1258 X OW -85 392 180 28 1259 X OW -19 257 -232 27 1260 X OW -142 578 6 24 1261 X OW 49 330 725 24 1262 X OW -33 445 220 25 1263 X OW 81 452 -119 28 1264 X OW -86 584 -317 30 1265 X OW -360 406 -149 27 1266 X OW -57 246 122 32 1267 X OW 53 548 487 26 1268 X OW 307 406 286 27 1269 X OW 60 396 -227 22 1270 X OW 349 496 603 32 1271 X OW 104 439 407 31 1272 X OW 121 430 129 31 1273 X OW 91 361 412 28 1274 X OW 188 631 269 29 1275 X OW -332 481 -398 61 1276 X OW 125 329 766 28 1277 X OW 294 589 437 28 1278 X OW -192 637 241 57 1279 X OW 28 335 653 26 1280 X OW 146 251 -49 28 1281 X OW -38 704 111 27 1282 X OW -240 367 168 26 1283 X OW 233 554 569 33 1284 X OW -48 290 -85 29 1285 X OW 174 436 537 34 1286 X OW -237 435 198 35 1287 X OW 75 489 -57 30 1288 X OW -8 178 28 37 1289 X OW 165 699 471 29 1290 X OW -227 224 -98 39 1291 X OW -170 515 -447 35 1292 X OW -202 284 -294 27 1293 X OW 60 357 392 30 1294 X OW 41 516 230 35 1295 X OW 41 614 354 36 1296 X OW -214 619 123 24 1297 X OW 45 312 606 32 1298 X OW 74 399 -9 30 1299 X OW -40 235 38 26 1300 X OW 350 516 769 34 1301 X OW 201 692 246 26 1302 X OW 196 552 451 30 1303 X OW 266 367 234 29 1304 X OW 307 398 711 28 1305 X OW -79 327 -41 34 1306 X OW -245 542 -239 37 1307 X OW 70 367 740 26 1308 X OW 240 483 520 34 1309 X OW -228 461 -140 35 1310 X OW 104 461

-28 27 1311 X OW -299 700 -8 26 1312 X OW -75 447 204 28 1313 X OW 327 345 566 29 1314 X OW -79 495 465 44 1315 X OW -23 541 173 32 1316 X OW 47 695 242 29 1317 X OW 32 448 767 30 1318 X OW 283 662 447 27 1319 X OW -241 410 -314 33 1320 X OW 147 443 394 30 1321 X OW -188 635 128 30 1322 X OW -6 607 -185 33 1323 X OW -361 413 0 31 1324 X OW 212 616 275 31 1325 X OW -362 291 -66 44 1326 X OW 23 662 69 28 1327 X OW 11 573 -292 30 1328 X OW -99 499 102 74 1329 X OW -61 288 -13 30 1330 X OW -330 498 -186 22 1331 X OW 116 477 73 29 1332 X OW -191 430 -1 29 1333 X OW -24 404 -59 34 1334 X OW -81 442 344 27 1335 X OW 9 683 61 41 1336 X OW -6 219 400 33 1337 X OW -38 274 -48 45 1338 X OW 152 406 227 29 1339 X OW -55 504 582 34 1340 X OW 256 315 706 39 1341 X OW 118 504 142 34 1342 X OW 12 496 -186 30 1343 X OW 132 721 230 35 1344 X OW 175 544 389 27 1345 X OW -176 620 106 66 1346 X OW -99 252 514 36 1347 X OW 60 307 199 34 1348 X OW 375 437 307 30 1349 X OW 208 719 254 33 1350 X OW 139 425 212 25 1351 X OW 268 480 227 28 1352 X OW -23 247 283 32 1353 X OW -78 473 -394 28 1354 X OW -15 539 509 34 1355 X OW -85 597 -147 25 1356 X OW 41 299 171 31 1357 X OW -250 576 -380 49 1358 X OW 213 313 256 33 1359 X OW -135 487 276 31 1360 X OW 319 394 343 25 1361 X OW 85 665 72 29 1362 X OW 161 362 512 32 1363 X OW -130 468 129 54 1364 X OW 222 539 811 42 1365 X OW -46 405 -346 30 1366 X OW 332 704 344 28 1367 X OW 300 535 329 38 1368 X OW 14 241 130 32 1369 X OW 100 661 49 27 1370 X OW -118 458 359 59 1371 X OW 227 317 496 25 1372 X OW 367 468 634 30 1373 X OW -130 531 279 27 1374 X OW 7 524 -171 34 1375 X OW 130 525 124 27 1376 X OW 247 528 789 33 1377 X OW 2 156 439 55 1378 X OW 158 237 -70 29 1379 X OW 119 168 74 28 1380 X OW -66 610 424 38 1381 X OW 146 720 297 53 1382 X OW 73 600 104 28 1383 X OW 350 547 796 38 1384 X OW -69 651 -53 29 1385 X OW -134 475 301 46 1386 X OW -308 542 -372 30 1387 X OW 345 361 712 50 END The following table contains one line for each atom in one HCV NS5B monomer as well as solvent molecules. The columns are: 1) residue number, 2) 1-letter amino acid code, 3) atom name, 4) x-coordinate multiPlied by 10, 5) y-coordinate multiPlied by 10, 6) z-coordinate multiPlied by 10, and 7) B-factor. The # coordinates of the second monomer (x.sub.2, y.sub.2, z.sub.2) are related to the coordinates of the first monomer (x.sub.1, y.sub.1, z.sub.1) listed below according to the following oPeration: x.sub.1 = x, .times. a.sub.11 + y.sub.1 .times. a.sub.12 + z.sub.1 .times. a.sub.13 + t.sub.1y.sub.2 = x, .times. a.sub.21 + y.sub.1 .times. a.sub.22 + z.sub.1 .times. a.sub.23 + t.sub.2z.sub.2 = x, .times. a.sub.3l + y.sub.1 .times. a.sub.32 + z.sub.1 .times. a.sub.33 + t.sub.3 where a.sub.11 a.sub.12 a.sub.13 -0.99978 0.01956 0.00754 a.sub.21 a.sub.22 a.sub.23 = 0.01940 0.99961 -0.01986 a.sub.31 a.sub.32 a.sub.33-0.00793 -0.01971 -0.99977 and t.sub.1 t.sub.2 t.sub.3 = -1.37838 0.34470 41.27925 The noncrystallograPhic oPeration described above should only be aPPlied to the HCV NS5B Protein atoms (i.e. residues 7 through 569). Following the Protein atoms are listed all discrete solvent molecules (residue X, atom OW) which were modeled into the asymmetric unit.

[0093]

Sequence CWU 1

1

1 1 576 PRT Hepatitis C virus VARIANT (335) amino acids at 335, 344 and 550 may be threonine or valine at 335, valine or alanine at 344 and arginine or glutamine at 550 1 Ala Ser His His His His His His Ser Tyr Thr Trp Thr Gly Ala Leu 1 5 10 15 Ile Thr Pro Cys Ala Ala Glu Glu Ser Lys Leu Pro Ile Asn Ala Leu 20 25 30 Ser Asn Ser Leu Leu Arg His His Asn Met Val Tyr Ala Thr Thr Ser 35 40 45 Arg Ser Ala Gly Leu Arg Gln Lys Lys Val Thr Phe Asp Arg Leu Gln 50 55 60 Val Leu Asp Asp His Tyr Arg Asp Val Leu Lys Glu Met Lys Ala Lys 65 70 75 80 Ala Ser Thr Val Lys Ala Lys Leu Leu Ser Val Glu Glu Ala Cys Lys 85 90 95 Leu Thr Pro Pro His Ser Ala Lys Ser Lys Phe Gly Tyr Gly Ala Lys 100 105 110 Asp Val Arg Asn Leu Ser Ser Lys Ala Val Asn His Ile His Ser Val 115 120 125 Trp Lys Asp Leu Leu Glu Asp Thr Val Thr Pro Ile Asp Thr Thr Ile 130 135 140 Met Ala Lys Asn Glu Val Phe Cys Val Gln Pro Glu Lys Gly Gly Arg 145 150 155 160 Lys Pro Ala Arg Leu Ile Val Phe Pro Asp Leu Gly Val Arg Val Cys 165 170 175 Glu Lys Met Ala Leu Tyr Asp Val Val Ser Thr Leu Pro Gln Val Val 180 185 190 Met Gly Ser Ser Tyr Gly Phe Gln Tyr Ser Pro Gly Gln Arg Val Glu 195 200 205 Phe Leu Val Asn Thr Trp Lys Ser Lys Lys Asn Pro Met Gly Phe Ser 210 215 220 Tyr Asp Thr Arg Cys Phe Asp Ser Thr Val Thr Glu Asn Asp Ile Arg 225 230 235 240 Val Glu Glu Ser Ile Tyr Gln Cys Cys Asp Leu Ala Pro Glu Ala Arg 245 250 255 Gln Ala Ile Lys Ser Leu Thr Glu Arg Leu Tyr Ile Gly Gly Pro Leu 260 265 270 Thr Asn Ser Lys Gly Gln Asn Cys Gly Tyr Arg Arg Cys Arg Ala Ser 275 280 285 Gly Val Leu Thr Thr Ser Cys Gly Asn Thr Leu Thr Cys Tyr Leu Lys 290 295 300 Ala Ser Ala Ala Cys Arg Ala Ala Lys Leu Gln Asp Cys Thr Met Leu 305 310 315 320 Val Asn Gly Asp Asp Leu Val Val Ile Cys Glu Ser Ala Gly Xaa Gln 325 330 335 Glu Asp Ala Ala Ser Leu Arg Xaa Phe Thr Glu Ala Met Thr Arg Tyr 340 345 350 Ser Ala Pro Pro Gly Asp Pro Pro Gln Pro Glu Tyr Asp Leu Glu Leu 355 360 365 Ile Thr Ser Cys Ser Ser Asn Val Ser Val Ala His Asp Ala Ser Gly 370 375 380 Lys Arg Val Tyr Tyr Leu Thr Arg Asp Pro Thr Thr Pro Leu Ala Arg 385 390 395 400 Ala Ala Trp Glu Thr Ala Arg His Thr Pro Val Asn Ser Trp Leu Gly 405 410 415 Asn Ile Ile Met Tyr Ala Pro Thr Leu Trp Ala Arg Met Ile Leu Met 420 425 430 Thr His Phe Phe Ser Ile Leu Leu Ala Gln Glu Gln Leu Glu Lys Ala 435 440 445 Leu Asp Cys Gln Ile Tyr Gly Ala Cys Tyr Ser Ile Glu Pro Leu Asp 450 455 460 Leu Pro Gln Ile Ile Glu Arg Leu His Gly Leu Ser Ala Phe Ser Leu 465 470 475 480 His Ser Tyr Ser Pro Gly Glu Ile Asn Arg Val Ala Ser Cys Leu Arg 485 490 495 Lys Leu Gly Val Pro Pro Leu Arg Val Trp Arg His Arg Ala Arg Ser 500 505 510 Val Arg Ala Arg Leu Leu Ser Gln Gly Gly Arg Ala Ala Thr Cys Gly 515 520 525 Lys Tyr Leu Phe Asn Trp Ala Val Lys Thr Lys Leu Lys Leu Thr Pro 530 535 540 Ile Pro Ala Ala Ser Xaa Leu Asp Leu Ser Gly Trp Phe Val Ala Gly 545 550 555 560 Tyr Ser Gly Gly Asp Ile Tyr His Ser Leu Ser Arg Ala Arg Pro Arg 565 570 575

Claims

We claim:

1. A crystalline composition comprising a HCV NS5B polypeptide.

2. The composition of claim 1 wherein the HCV NS5B polypeptide comprises tNS5B.

3. A composition comprising a NS5B protein having at least one amino acid substitution at position 335, 344 or 550 of SEQ ID NO: 1.

4. The composition according to claim 3 wherein the amino acid substitution at position 335 is a threonine to a valine substitution.

5. The composition according to claim 3, wherein the amino acid substitution at position 344 is a valine to an alanine substitution.

6. The composition according to claim 3, wherein the amino acid substitution at position 550 is an arginine to a glutamine substitution.

7. A composition comprising a NS5B protein having at least one amino acid substitution at position 335, 344 or 550 of a histidine-tagged NS5B protein.

8. The composition according to claim 7, wherein the NS5B protein comprises SEQ ID NO: 1.

9. A method of preparing purified, crystalline HCV NS5B comprising the steps of: (a) stabilizing a NS5B protein preparation in a solution containing a protein stabilizing agent; (b) subjecting the NS5B protein preparation to cation exchange chromatography in a buffer containing glycine; and (c) allowing crystals to form in a precipitant containing a protein stabilizing agent, a salt and polyethylene glycol under conditions in which crystallization occurs.

10. The method of claim 9 wherein the NS5B protein preparation comprises tNS5B.

11. The method of claim 9 wherein the glycine is removed from the NS5B protein preparation after cation exchange chromatography.

12. The method of claim 11, wherein the glycine is removed by dialysis.

13. The method of claim 9 wherein the crystals are allowed to form using a microbatch method.

14. The method of claim 9, wherein the crystals are allowed to form using vapor diffusion.

15. The method of claim 9, wherein the protein stabilizing agent is glycerol.

16. The method of claim 15, wherein the glycerol is provided at a concentration of 10% (volume/volume).

17. The method of claim 9, wherein glycine is provided at a concentration of one molar.

18. The method of claim 9, wherein the polyethylene glycol has a molecular weight of 4000-5000 daltons.

19. A machine-readable data storage medium, comprising a data storage material encoded with machine readable data, wherein the data is defined by the structure coordinates of a NS5B polypeptide according to Table 1, or a homologue thereof wherein said homologue comprises alpha carbon atoms that have a root mean square deviation between equivalent alpha carbon atoms of the polypeptide of not more than 3.0 .ANG..

20. A method of obtaining structural information concerning a molecule of unknown structure by using the structure coordinates set forth in Table 1, comprising the steps of: (a) generating x-ray diffraction data from said crystallized molecule; and (b) applying crystallographic phases derived from at least a portion of the structure coordinates set forth in Table 1 to said x-ray diffraction pattern to generate a three-dimensional electron density map of at least a portion of the molecule.

21. The method of claim 20, wherein the molecule is a polymerase.

22. A method of obtaining structural information concerning a molecular complex of unknown structure by using the structure coordinates set forth in Table 1, comprising the steps of: (a) generating x-ray diffraction data from said crystallized molecule; and (b) applying crystallographic phases derived from at least a portion of the structure coordinates set forth in Table 1 to said x-ray diffraction pattern to generate a three-dimensional electron density map of at least a portion of the molecule.

23. The method of claim 22, wherein the molecular complex contains a NS5B polypeptide.