US 20090062286A1

(19) United States

(12) Patent Application Publication (10) Pub. No.: US 2009/0062286 A1
Foreman et al. (43) Pub. Date: Mar. 5, 2009

(54) CRYSTAL STRUCTURE OF SMYD3 PROTEIN C07D 257/04 (2006.01)

A611; 31/421 (2006.01)
(76) Inventors: Kenneth William Foreman, A61K 31/519 (2006.01)
Farmingdale; NY (US); Frances E. A61P 35/00 (2006.01)
Park; San Diego; CA (Us); Lee A611; 31/53 75 (2006.01)
Arnold; East lslip; NY (Us) A611; 31/433 (2006.01)
C07D 263/04 (2006.01)
Correspondence Address: C07D 285/135 (2006.01)
MINTZ, LEVIN, COHN, EERRIS, GLOVSKY com 48 7/04 (2006.01)
AND PoPEo, P.C C07D 265/30 (2006.01)
ONE FINANCIAL CENTER (52) US. Cl. ....... .. 514/237.8; 435/193; 703/11; 435/71;
BOSTON MA 02111 (Us) 548/253; 548/215; 548/138; 544/263; 544/165;
(21) Appl NO_ 12/115 089 514/381;514/374;514/363;514/25216
57 ABSTRACT
(22) Filed: May 5, 2008 ( )
The invention relates to SMYD3 methyltransferase
Related US. Application Data (SMYD3); SMYD3 binding pockets or SMYD3 -lil;e binding
pockets. The invention relates to a computer comprising a
(60) Provisional application No. 60/ 915,969; ?led on May data storage medium encoded With the structure coordinates
4; 2007. of such binding pockets. The invention also relates to meth
ods of using the structure coordinates to solve the structure of
Publication Classi?cation homologous proteins or protein complexes. The invention
(51) Int. Cl. relates to methods of using the structure coordinates to screen
A61K 31/41 (2006.01) for and design compounds that bind to SMYD3 methyltrans
C12N 9/10 (2006.01) ferase protein; complexes of SMYD3 methyltransferase pro
G06G 7/58 (2006.01) tein; homologues thereof; or SMYD3 -lil;e protein or protein
G01N 33/53 (2006.01 ) complexes.
Patent Application Publication Mar. 5, 2009 Sheet 1 of 138 US 2009/0062286 A1

Figure 1 A- 1

Atom Type Residue # X Y Z Occ B Type

ATOM 1 N LEU A 4 7 . 063 22 .251 15 .190 1 . 00 41 .54 N

ATOM 2 CA LEU A 4 6 . 135 21 . 536 16 .128 1 . 00 39 .72 C
ATOM 3 C LEU A 4 5 .386 20 .368 15 .466 1 . 00 36 .25 C
ATOM 4 O LEU A 4 4 . 807 20 .486 14 .381 1 . 00 37 .30 O
ATOM 5 CB LEU A 4 5 . 143 22 . 515 16 .768 1 . 00 42 .11 C
ATOM 6 N LYS A 5 5 .393 19 .236 16 .141 1 . 00 30 .21 N
ATOM 7 CA LYS A 5 4 . 771 18 . 046 15 .600 1 . 00 28 .72 C
ATOM 8 C LYS A 5 3 .365 17 . 828 16 .166 1 . 00 26 . 04 C
ATOM 9 O LYS A 5 2 . 663 16 . 880 15 .777 1 . 00 24 .51 O
ATOM 10 CB LYS A 5 5 . 693 16 . 853 15 .820 1 . 00 29 .65 C
ATOM 11 CG LYS A 5 7 . 120 17 . 177 15 .426 1 . 00 33 .63 C
ATOM 12 CD LYS A 5 8 . 074 16 . 059 15 .767 1 . 00 44 .36 C
ATOM 13 CE LYS A 5 9 .459 16 . 380 15 .221 1 . 00 47 .74 C
ATOM 14 NZ LYS A 5 10 . 339 15 . 186 15 .218 1 . 00 51 .11 N
ATOM 15 N VAL A 6 2 . 948 18 . 758 17 . 036 1 . 00 24 . 07 N
ATOM 16 CA VAL A 6 1 . 676 18 . 674 17 .743 1 . 00 23 .32 C
ATOM 17 C VAL A 6 0 . 927 20 . 013 17 .724 1 . 00 23 .78 C
ATOM 18 O VAL A 6 1 .
547 21 . 046 17 .537 1 . 00 23 .52 O
ATOM 19 CB VAL A 6 1 .
897 18 .224 19 .215 1 . 00 21 .13 C
ATOM 20 CG1 VAL A 6 2 .
741 16 . 965 19 .245 1 . 00 19 .51 C
ATOM 21 CG2 VAL A 6 2 .
558 19 .312 20 . 028 1 . 00 19 .28 C
ATOM 22 N GLU A 7 0 .392 19 . 968 17 . 906 1 . 00 22 . 05 N
ATOM 23 CA GLU A 7 *1 .238 21 . 158 18 . 002 1 . 00 22 . 01 C
ATOM 24 C GLU A 7 *2 .475 20 . 939 18 .875 1 . 00 22 . 99 C
ATOM 25 O GLU A 7 e3 . 041 19 . 828 18 . 931 1 . 00 24 .23 O
ATOM 26 CE GLU A 7 1 . 716 21 . 590 16 .608 1 . 00 26 .26 C
ATOM 27 CG GLU A 7 2 . 596 20 . 553 15 . 921 1 . 00 22 .39 C
ATOM 28 CD GLU A 7 2 . 908 20 . 894 14 .481 1 . 00 25 .69 C
ATOM 29 OE1 GLU A 7 2 .370 21 . 907 13 . 973 1 . 00 39 . 06 O
ATOM 30 0E2 GLU A 7 3 . 708 20 . 161 13 .880 1 . 00 31 .11 O
ATOM 31 N LYS A 8 2 . 877 22 . 010 19 .559 1 . 00 21 .79 N
ATOM 32 CA LYS A 8 4 . 123 22 . 070 20 .277 1 . 00 24 .39 C
ATOM 33 C LYS A 8 5 .305 21 . 986 19 .290 1 . 00 23 .77 C
ATOM 34 O LYS A 8 *5 .225 22 .488 18 .171 1 . 00 27 .89 O
ATOM 35 CE LYS A 8 e4 . 184 23 .372 21 . 075 1 . 00 24 .44 C
ATOM 36 CG LYS A 8 *5 .496 23 . 608 21 .847 1 . 00 26 . 05 C
ATOM 37 CD LYS A 8 5 . 360 24 . 820 22 .740 1 . 00 22 . 00 C
ATOM 38 CE LYS A 8 5 . 514 26 . 093 21 . 958 1 . 00 43 .33 C
ATOM 39 NZ LYS A 8 6 . 959 26 .416 21 .777 1 . 00 53 .70 N
ATOM 40 N PHE A 9 6 .365 21 .304 19 .693 1 . 00 22 .77 N
ATOM 41 CA PHE A 9 7 . 617 21 .278 18 . 936 1 . 00 23 .73 C
ATOM 42 C PHE A 9 8 . 778 21 . 068 19 .879 1 . 00 25 .20 C
ATOM 43 O PHE A 9 8 . 580 20 . 688 21 . 019 1 . 00 23 .73 O
ATOM 44 CE PHE A 9 7 . 576 20 .212 17 .823 1 . 00 22 .67 C
ATOM 45 CG PHE A 9 e7 . 782 18 . 793 18 .304 1 . 00 24 . 03 C
ATOM 46 CD1 PHE A 9 e8 . 968 18 . 115 18 . 009 1 . 00 26 .78 C
ATOM 47 CE1 PHE A 9 e9 . 168 16 . 809 18 .410 1 . 00 23 .25 C
ATOM 48 CZ PHE A 9 8 . 179 16 . 152 19 .147 1 . 00 25 .25 C
ATOM 49 CE2 PHE A 9 6 . 990 16 . 811 19 .451 1 . 00 26 .22 C
ATOM 50 CD2 PHE A 9 6 . 793 18 . 130 19 . 020 1 . 00 24 . 93 C
ATOM 51 N ALA A 10 9 . 992 21 .358 19 .415 1 . 00 25 .65 N
ATOM 52 CA ALA A 10 11 . 197 21 . 092 20 .192 1 . 00 27 .72 C
ATOM 53 C ALA A 10 11 . 774 19 . 737 19 .803 1 . 00 27 .42 C
ATOM 54 O ALA A 10 12 . 063 19 .484 18 .636 1 . 00 28 .78 O
Patent Application Publication Mar. 5, 2009 Sheet 2 of 138 US 2009/0062286 A1

Figlire 1A-2
Atom Type Residue # X Y Z Occ E Type

ATOM 55 CE ALA A 10 12 .234 22 .214 20 . 000 1 . 00 29 .48 C

ATOM 56 N THR A 11 11 .884 18 .851 20 .778 1 . 00 27 .44 N
ATOM 57 CA THR A 11 412 .457 17 .533 20 .563 1 . 00 25 .52 C
ATOM 58 C THR A 11 13 . 979 17 .680 20 .576 1 . 00 25 . 90 C
ATOM 59 O THR A 11 14 .501 18 .704 21 . 030 1 . 00 30 .24 O
ATOM 60 CE THR A 11 12 . 065 16 .502 21 .687 1 . 00 23 .64 C
ATOM 61 OG1 THR A 11 412 .752 16 .824 22 .898 1 . 00 19 .17 O
ATOM 62 CG2 THR A 11 10 .575 16 .435 21 . 927 1 . 00 17 . 91 C
ATOM 63 N ALA A 12 14 .678 16 .643 20 .124 1 . 00 29 .61 N
ATOM 64 CA ALA A 12 16 .136 16 .589 20 .198 1 . 00 30 .56 C
ATOM 65 C ALA A 12 16 .672 16 .665 21 .616 1 . 00 31 .73 C
ATOM 66 O ALA A 12 417 .481 17 .539 21 . 928 1 . 00 34 . 08 O
ATOM 67 CB ALA A 12 16 .661 15 .317 19 .502 1 . 00 31 . 04 C
ATOM 68 N ASN A 13 16 .211 15 .764 22 .480 1 . 00 33 .18 N
ATOM 69 CA ASN A 13 16 .862 15 .525 23 .765 1 . 00 34 .88 C
ATOM 70 C ASN A 13 15 . 941 15 .564 24 . 986 1 . 00 35 . 01 C
ATOM 71 O ASN A 13 *16 .368 15 .223 26 . 090 1 . 00 36 . 02 O
ATOM 72 CB ASN A 13 17 .551 14 .160 23 .744 1 . 00 37 .36 C
ATOM 73 CG ASN A 13 18 .511 14 . 008 22 .583 1 . 00 44 .39 C
ATOM 74 OD1 ASN A 13 18 .328 13 .141 21 .728 1 . 00 52 .13 O
ATOM 75 ND2 ASN A 13 19 .538 14 .859 22 .541 1 . 00 49 .21 N
ATOM 76 N ARG A 14 414 .679 15 . 947 24 .809 1 . 00 31 . 07 N
ATOM 77 CA ARG A 14 13 .768 15 .888 25 . 949 1 . 00 25 .54 C
ATOM 78 C ARG A 14 12 .874 17 .137 26 . 061 1 . 00 24 .27 C
ATOM 79 O ARG A 14 11 .718 17 . 049 26 .485 1 . 00 21 .23 O
ATOM 80 CE ARG A 14 12 . 979 14 .566 25 . 938 1 . 00 22 .46 C
ATOM 81 CG ARG A 14 412 .353 14 .226 24 .596 1 . 00 29 .81 C
ATOM 82 CD ARG A 14 11 .251 13 .209 24 .673 1 . 00 42 .63 C
ATOM 83 NE ARG A 14 11 .763 11 .848 24 .697 1 . 00 51 .24 N
ATOM 84 CZ ARG A 14 11 . 057 10 .773 24 .352 1 . 00 53 .29 C
ATOM 85 NHl ARG A 14 9 .803 10 .890 23 . 927 1 . 00 50 .78 N
ATOM 86 NH2 ARG A 14 411 .622 9 .574 24 .412 1 . 00 53 .28 N
ATOM 87 N GLY A 15 13 .424 18 .298 25 .675 1 . 00 21 .15 N
ATOM 88 CA GLY A 15 12 .710 19 .579 25 .782 1 . 00 20 . 97 C
ATOM 89 C GLY A 15 11 .625 19 .773 24 .746 1 . 00 22 .61 C
ATOM 90 O GLY A 15 11 .773 19 .373 23 .587 1 . 00 25 . 90 O
ATOM 91 N ASN A 16 410 .545 20 .426 25 .143 1 . 00 19 .70 N
ATOM 92 CA ASN A 16 9 .411 20 .555 24 .245 1 . 00 20 .27 C
ATOM 93 C ASN A 16 8 .550 19 .302 24 .341 1 . 00 18 .63 C
ATOM 94 O ASN A 16 8 .608 18 .586 25 .346 1 . 00 21 .60 O
ATOM 95 CE ASN A 16 8 .634 21 .819 24 .574 1 . 00 20 . 96 C
ATOM 96 CG ASN A 16 *9 .490 23 . 048 24 .437 1 . 00 24 .16 C
ATOM 97 OD1 ASN A 16 10 .185 23 .196 23 .436 1 . 00 21 .87 O
ATOM 98 ND2 ASN A 16 9 .506 23 .892 25 .461 1 . 00 22 . 90 N
ATOM 99 N GLY A 17 7 .808 19 . 017 23 .290 1 . 00 16 .31 N
ATOM 100 CA GLY A 17 6 .869 17 .898 23 .287 1 . 00 17 . 92 C
ATOM 101 C GLY A 17 *5 .643 18 .283 22 .472 1 . 00 17 .72 C
ATOM 102 O GLY A 17 *5 .543 19 .402 22 . 010 1 . 00 19 .53 O
ATOM 103 N LEU A 18 4 .732 17 .342 22 .306 1 . 00 17 . 94 N
ATOM 104 CA LEU A 18 3 .567 17 .537 21 .478 1 . 00 20 . 08 C
ATOM 105 C LEU A 18 3 .595 16 .505 20 .328 1 . 00 17 .16 C
ATOM 106 O LEU A 18 e3 . 945 15 .352 20 .545 1 . 00 17 . 99 O
ATOM 107 CB LEU A 18 *2 .306 17 .415 22 .336 1 . 00 15 . 91 C
ATOM 108 CG LEU A 18 1 . 000 17 . 943 21 .777 1 . 00 22 .70 C
ATOM 109 CD1 LEU A 18 1 . 046 19 .426 21 .741 1 . 00 23 .71 C
Patent Application Publication Mar. 5, 2009 Sheet 3 of 138 US 2009/0062286 A1

Figure 1A-3
Atom Type Residue # X Y Z 000 E Type

ATOM 110 CD2 LEU A 18 0 . 159 1'7 .518 22 .664 1 . 00 20 . 60 C

ATOM 111 N ARG A 19 3 .201 16 . 925 19 .120 1 . 00 19 .43 N
ATOM 112 CA ARG A 19 e3 . 104 16 . 026 17 . 965 1 . 0O 2O . 13 C
ATOM 113 C ARG A 19 1 . 817 16 .137 17 .135 1 . 00 18 .42 C
ATOM 114 O ARG A 19 1 . 152 17 .141 17 .188 1 . 00 22 . 98 O
ATOM 115 CB ARG A 19 4 .351 16 .105 17 . 082 1 . 00 23 . 86 C
ATOM 116 CG ARG A 19 4 .424 17 .280 16 .159 1 . 00 18 . 09 C
ATOM 117 CD ARG A 19 e5 . 824 17 .359 15 .547 1 . 00 25 . 54 C
ATOM 118 NE ARG A 19 6 . 079 18 .680 14 . 973 1 . 00 31 . 86 N
ATOM 119 CZ ARG A 19 7 .264 19 .121 14 .538 1 . 00 40 . 98 C
ATOM 120 NH1 ARG A 19 8 .346 18 .350 14 .606 1 . 0O 39 . 85 N
ATOM 121 NH2 ARG A 19 7 .370 20 .354 14 . 041 1 . 00 36 . 15 N
ATOM 122 N ALA A 20 *1 .459 15 . 067 16 .428 1 . 0O 20 .42 N
ATOM 123 CA ALA A 20 0 .299 15 . 029 15 .582 1 . 0O 20 . 52 C
ATOM 124 C ALA A 20 0 .493 15 . 945 14 .359 1 . 00 24 . 98 C
ATOM 125 O ALA A 20 1 . 530 15 .893 13 .685 1 . 00 25 .47 O
ATOM 126 CB ALA A 20 0 . 035 13 .622 15 .116 1 . 00 19 . 61 C
ATOM 127 N VAL A 21 0 . 517 16 .762 14 .100 1 . 0O 26 . 34 N
ATOM 128 CA VAL A 21 0 . 566 17 .621 12 . 907 1 . 00 29 . 92 C
ATOM 129 C VAL A 21 1 . 189 16 .852 11 .745 1 . 00 31 . 17 C
ATOM 130 O VAL A 21 0 . 851 17 . 077 10 .586 1 . 00 32 . 68 O
ATOM 131 CB VAL A 21 1 .322 18 . 935 13 .188 1 . 00 30 . 15 C
ATOM 132 CG1 VAL A 21 1 . 388 19 .828 11 . 940 1 . 00 33 . 77 C
ATOM 133 CG2 VAL A 21 0 . 629 19 .694 14 .322 1 . 0O 31 .41 C
ATOM 134 N THR A 22 2 . 067 15 . 914 12 . 086 1 . 00 32 .40 N
ATOM 135 CA THR A 22 2 . 790 15 . 066 11 .135 1 . 00 31 . 77 C
ATOM 136 C THR A 22 2 . 702 13 .609 11 .607 1 . 00 30 . 70 C
ATOM 137 O THR A 22 2 .336 13 .368 12 .770 1 . 00 27 . 80 O
ATOM 138 CB THR A 22 4 .286 15 .484 11 . 037 1 . 00 34 . 82 C
ATOM 139 OG1 THR A 22 4 . 891 15 .455 12 .338 1 . 00 38 .29 O
ATOM 140 CG2 THR A 22 4 .431 16 .882 10 .458 1 . 00 37 .34 C
ATOM 141 N PRO A 23 3 . 018 12 .627 10 .721 1 . 00 30 . 55 N
ATOM 142 CA PRO A 23 3 . 123 11 .238 11 .179 1 . 00 28 . 51 C
ATOM 143 C PRO A 23 4 .232 11 . 093 12 .223 1 . 0O 28 . 53 C
ATOM 144 O PRO A 23 5 .307 11 .658 12 . 052 1 . 00 30 . 53 O
ATOM 145 CB PRO A 23 3 . 532 10 .477 9 . 914 1 . 00 29 . 94 C
ATOM 146 CG PRO A 23 3 . 104 11 .361 8 .771 1 . 00 34 . 14 C
ATOM 147 CD PRO A 23 3 .329 12 .749 9 .280 1 . 00 29 . 63 C
ATOM 148 N LEU A 24 3 . 978 10 .341 13 .294 1 . 0O 28 . 15 N
ATOM 149 CA LEU A 24 4 . 974 10 .146 14 .346 1 . 00 23 . 88 C
ATOM 150 C LEU A 24 5 .400 8 .686 14 .472 1 . 0O 23 .40 C
ATOM 151 O LEU A 24 4 . 594 7 .746 14 .299 1 . 0O 23 . 12 O
ATOM 152 CB LEU A 24 4 .448 10 .671 15 .691 1 . 00 24 . 00 C
ATOM 153 CG LEU A 24 3 . 770 12 . 044 15 .738 1 . 00 26 . 86 C
ATOM 154 CD1 LEU A 24 2 . 962 12 .220 17 . 057 1 . 00 16 .26 C
ATOM 155 CD2 LEU A 24 4 . 758 13 .180 15 .471 1 . 00 25 . 10 C
ATOM 156 N ARG A 25 6 . 681 8 .505 14 .749 1 . 00 23 . 17 N
ATOM 157 CA ARG A 25 7 .280 7 .199 14 . 906 1 . 00 21 . 83 C
ATOM 158 C ARG A 25 7 .488 6 .891 16 .409 1 . 0O 22 .33 C
ATOM 159 O ARG A 25 7 . 618 7 .825 17 .215 1 . 00 19 . 69 O
ATOM 160 CB ARG A 25 8 . 630 7 .158 14 .191 1 . 00 27 .42 C
ATOM 161 N PRO A 26 7 . 554 5 .599 16 .765 1 . 00 21 . 93 N
ATOM 162 CA PRO A 26 7 . 810 5 .220 18 .165 1 . 00 21 .26 C
ATOM 163 C PRO A 26 9 . 093 5 .820 18 .681 1 . 0O 20 . 63 C
ATOM 164 O PRO A 26 10 . 149 5 .657 18 . 057 1 . 00 20 . 58 O
Patent Application Publication Mar. 5, 2009 Sheet 4 of 138 US 2009/0062286 A1

Figlire 1A-4
Atom Type Residue # X Y Z Occ E Type

ATOM 165 CB PRO A 26 7 .930 3 .693 18 . 095 1 . 00 20 . 05 C

ATOM 166 CO PRO A 26 7 .147 3 .335 16 . 902 1 . 00 24 .70 C
ATOM 167 CD PRO A 26 7 .385 4 . 400 15 . 917 1 . 00 2O 59 C
ATOM 168 N GLY A 27 9 .010 6 .506 19 .820 1 . 00 17 .78 N
ATOM 169 CA GLY A 27 1O . 176 7 . 107 20 .438 1 . 00 19 .20 C
ATOM 170 C GLY A 27 10 .368 8 .557 20 . 066 1 . 00 18 .67 C
ATOM 171 O GLY A 27 11 .211 9 . 228 20 . 629 1 . 00 22 .20 O
ATOM 172 N GLU A 28 9 .585 9. 066 19 .120 1 . 00 20 .44 N
ATOM 173 CA GLU A 28 9 .788 10.433 18 .664 1 . 00 18 . 04 C
ATOM 174 C GLU A 28 9 .454 11 . 455 19 . 769 1 . 00 19 . 86 C
ATOM 175 O GLU A 28 8 .371 11.419 20 .370 1 . 00 18 .49 O
ATOM 176 C13 GLU A 28 8 .941 10.703 17 .433 1 . 00 20 .82 C
ATOM 177 CO GLU A 28 9 .295 11. 996 16 .690 1 . 00 26 .17 C
ATOM 178 CD GLU A 28 8 . 778 12 . 003 15 .254 1 . 00 35 . 01 C
ATOM 179 0E1 GLU A 28 8 .389 10. 928 14 .730 1 . 00 33 .87 O
ATOM 180 OE2 GLU A 28 8 .781 13 . 086 14 .644 1 . 00 39 . 92 O
ATOM 181 N LEU A 29 10 .385 12 . 369 20 . 017 1 . 00 21 . 19 N
ATOM 182 CA LEU A 29 1O . 157 13 . 447 20 . 973 1 . 0O 21 .42 C
ATOM 183 C LEU A 29 9 . 164 14 . 474 20 .441 1 . 00 21 . 91 C
ATOM 184 O LEU A 29 9 .363 15. 078 19 .373 1 . 00 22 . 06 O
ATOM 185 CB LEU A 29 11 .494 14 . 103 21 .347 1 . 00 23 .27 C
ATOM 186 CO LEU A 29 11 . 539 15 . 214 22 .404 1 . 00 27 .23 C
ATOM 187 CD1 LEU A 29 11 . 069 14 . 743 23 . 795 1 . 00 21 . 57 C
ATOM 188 CD2 LEU A 29 12 . 936 15 . 786 22 .452 1 . 00 25 . 91 C
ATOM 189 N LEU A 30 8 .098 14 .673 21 .204 1 . 00 18 . 08 N
ATOM 190 CA LEU A 30 7 .014 15.556 20 .828 1 . 00 18 .18 C
ATOM 191 C LEU A 30 7 . 058 16 . 946 21 .474 1 . 00 17 . 76 C
ATOM 192 O LEU A 30 6 .673 17. 951 20 .845 1 . 00 20 .73 O
ATOM 193 CE LEU A 30 5 . 682 14 . 859 21 . 147 1 . 0O 16 . 18 C
ATOM 194 CG LEU A 30 5 .498 13 . 463 20 . 565 1 . 00 16 .41 C
ATOM 195 CD1 LEU A 30 4 . 063 13 . 013 20 . 786 1 . 0O 17 .47 C
ATOM 196 CD2 LEU A 30 5 .846 13 .495 19 . 061 1 . 00 21 .36 C
ATOM 197 N PHE A 31 7 .480 16 . 997 22 . 736 1 . 00 19 . 08 N
ATOM 198 CA PHE A 31 7 . 542 18 . 231 23 . 529 1 . 00 17 . 99 C
ATOM 199 C PHE A 31 8 .467 17. 980 24 .718 1 . 00 2O .89 C
ATOM 200 O PHE A 31 8 . 612 16 . 839 25 . 174 1 . 00 22 . 13 O
ATOM 201 CB PHE A 31 6 .126 18 .646 23 . 999 1 . 00 17 .24 C
ATOM 202 CC PHE A 31 5 .985 20.120 24 .305 1 . 00 23 .20 C
ATOM 203 CD1 PHE A 31 5 .790 21. 051 23 .285 1 . 00 29 . 97 C
ATOM 204 CE1 PHE A 31 5 .649 22 .428 23 .592 1 . 00 23 . 04 C
ATOM 205 CZ PHE A 31 5 . 732 22 . 857 24 . 904 1 . 00 24 .21 C
ATOM 206 CE2 PHE A 31 5 .911 21. 931 25 . 929 1 . 00 30 .22 C
ATOM 207 CD2 PHE A 31 6 .046 20.575 25 .622 1 . 00 25 .17 C
ATOM 208 N ARG A 32 9 . 183 19 . 006 25 . 145 1 . 00 18 . 94 N
ATOM 209 CA ARG A 32 9 .823 18 . 954 26 .421 1 . 00 20 .65 C
ATOM 210 C ARG A 32 9 . 596 20 . 194 27 .207 1 . 0O 18 . 73 C
ATOM 211 O ARG A 32 9 .529 21.292 26 .652 1 . 00 18 .26 O
ATOM 212 CB ARG A 32 11 .307 18 .659 26 .323 1 . 00 21 .45 C
ATOM 213 CG ARG A 32 12 . 124 19 . 527 25 .429 1 . 0O 25 . 37 C
ATOM 214 CD ARG A 32 13 .403 18 .784 25 . 039 1 . 00 26 .37 C
ATOM 215 NE ARG A 32 14 .231 18 . 468 26 .204 1 . 0O 23 . 19 N
ATOM 216 CZ ARG A 32 15 .477 17 . 987 26 . 154 1 . 0O 26 . 92 C
ATOM 217 NHl ARG A 32 16 . 072 17 . 771 24 . 985 1 . 00 26 . 65 N
ATOM 218 NH2 ARG A 32 16 . 139 17 . 750 27 .288 1 . 00 24 . 54 N
ATOM 219 N SER A 33 9 .547 20 . 046 28 .518 1 . 00 22 .89 N
Patent Application Publication Mar. 5, 2009 Sheet 5 of 138 US 2009/0062286 A1

Figure 1A-5
Atom Type Residue Occ B Type

ATOM 220 CA SER A 33 9 .197 21 . 178 29 . 333 1 . 00 22 .44 C

ATOM 221 C SER A 33 9 .736 21 . 072 30 . 739 1 . 00 21 .70 C
ATOM 222 O SER A 33 9 .747 19 . 990 31 .340 1 . 00 21 .44 O
ATOM 223 CB SER A 33 7 .658 21 .245 29 .371 1 . 00 26 .82 C
ATOM 224 OG SER A 33 7 .225 22 .324 30 . 127 1 . 00 22 . 99 O
ATOM 225 N ASP A 34 10 .160 22 .220 31 .265 1 . 00 19 .33 N
ATOM 226 CA ASP A 34 10 .348 22 .378 32 . 675 1 . 00 19 .53 C
ATOM 227 C ASP A 34 8 . 972 22 . 727 33 .244 1 . 00 17 .38 C
ATOM 228 O ASP A 34 8 . 082 23 . 137 32 .494 1 . 00 18 . 07 O
ATOM 229 CB ASP A 34 11 .362 23 .499 32 . 983 1 . 00 22 . 09 C
ATOM 230 CG ASP A 34 12 .787 23 . 100 32 . 653 1 . 00 25 .34 C
ATOM 231 OD1 ASP A 34 13 .157 21 . 925 32 . 892 1 . 00 31 .30 O
ATOM 232 OD2 ASP A 34 13 .541 23 . 968 32 . 173 1 . 00 40 .82 O
ATOM 233 N PRO A 35 8 .803 22 . 580 34 . 564 1 . 00 17 . 97 N
ATOM 234 CA PRO A 35 7 .510 22 . 914 35 . 199 1 . 00 18 .14 C
ATOM 235 C PRO A 35 7 .225 24 .405 35 . 163 1 . 00 17 . 05 C
ATOM 236 O PRO A 35 8 .158 25 .206 35 . 152 1 . 00 20 .58 O
ATOM 237 CB PRO A 35 7 .685 22 .426 36 . 634 1 . 00 21 .14 C
ATOM 238 CG PRO A 35 8 . 988 21 . 633 36 . 635 1 . 00 16 .19 C
ATOM 239 CD PRO A 35 9 .800 22 . 144 35 . 547 1 . 00 16 .49 C
ATOM 240 N LEU A 36 5 . 952 24 . 787 35 . 063 1 . 00 18 .82 N
ATOM 241 CA LEU A 36 5 .573 26 . 178 35 .371 1 . 00 20 .46 C
ATOM 242 C LEU A 36 5 . 919 26 .452 36 . 840 1 . 00 19 .44 C
ATOM 243 O LEU A 36 6 .499 27 . 507 37 . 171 1 . 00 19 .11 O
ATOM 244 CB LEU A 36 4 . 097 26 .437 35 . 112 1 . 00 23 .10 C
ATOM 245 CG LEU A 36 3 .555 27 . 772 35 . 650 1 . 00 18 . 04 C
ATOM 246 CD1 LEU A 36 4 . 077 28 . 992 34 . 862 1 . 00 22 .68 C
ATOM 247 CD2 LEU A 36 2 . 039 27 . 727 35 . 616 1 . 00 19 .69 C
ATOM 248 N ALA A 37 5 .599 25 .474 37 . 690 1 . 00 17 .38 N
ATOM 249 CA ALA A 37 5 . 906 25 .462 39 . 117 1 . 00 18 .54 C
ATOM 250 C ALA A 37 5 . 921 24 . 010 39 . 583 1 . 00 18 .21 C
ATOM 251 O ALA A 37 5 .228 23 .200 39 . 010 1 . 00 18 .22 O
ATOM 252 CB ALA A 37 4 .840 26 .234 39 . 917 1 . 00 19 .67 C
ATOM 253 N TYR A 38 6 .717 23 . 707 40 . 611 1 . 00 1'7 .74 N
ATOM 254 CA TYR A 38 6 .782 22 . 382 41 .227 1 . 00 18 .57 C
ATOM 255 C TYR A 38 '7 .307 22 .483 42 . 617 1 . 00 19 .70 C
ATOM 256 O TYR A 38 7 . 909 23 .489 42 . 962 1 . 00 24 .27 O
ATOM 257 CB TYR A 38 7 .700 21 .432 40 .411 1 . 00 18 .14 C
ATOM 258 CG TYR A 38 9 .176 21 . 695 40 . 575 1 . 00 15 .45 C
ATOM 259 CD1 TYR A 38 9 . 996 20 . 780 41 .251 1 . 00 17 .84 C
ATOM 260 CE1 TYR A 38 11 .328 21 . 007 41 .392 1 . 00 21 .73 C
ATOM 261 CZ TYR A 38 11 .883 22 . 171 40 . 872 1 . 00 18 .70 C
ATOM 262 OH TYR A 38 13 .227 22 .417 40 . 982 1 . 00 23 .73 O
ATOM 263 CB2 TYR A 38 11 .108 23 . 086 40 . 198 1 . 00 24 .10 C
ATOM 264 CD2 TYR A 38 9 .762 22 . 836 40 . 041 1 . 00 17 .87 C
ATOM 265 N THR A 39 '7 .102 21 .412 43 . 390 1 . 00 18 .40 N
ATOM 266 CA THR A 39 '7 .643 21 .258 44 . 705 1 . 00 23 . 00 C
ATOM 267 C THR A 39 '7 . 907 19 . 775 44 . 964 1 . 00 21 .46 C
ATOM 268 O THR A 39 7 .239 18 . 929 44 .399 1 . 00 20 .29 O
ATOM 269 CB THR A 39 6 .678 21 . 856 45 . 783 1 . 00 21 .75 C
ATOM 270 0G1 THR A 39 7 .255 21 . 751 47 . 082 1 . 00 26 .37 O
ATOM 271 CG2 THR A 39 5 .334 21 . 183 45 . 761 1 . 00 23 .15 C
ATOM 272 N VAL A 40 8 .889 19 .499 45 . 819 1 . 00 20 .33 N
ATOM 273 CA VAL A 40 9 .150 18 . 182 46 .371 1 . 00 20 . 95 C
ATOM 274 C VAL A 40 7 .864 17 . 730 47 . 063 1 . 00 21 . 90 C
Patent Application Publication Mar. 5, 2009 Sheet 6 of 138 US 2009/0062286 A1

Figure lA-6
Atom Type Residue X Y Z Occ E Type

ATOM 275 O VAL A 40 '7 .160 18 . 547 47 . 608 1 . 00 22 . 92 O

ATOM 276 CB VAL A 40 10 .401 18 . 188 47 .333 1 . 00 23 .68 C
ATOM 277 CG1 VAL A 40 10 .224 19 . 165 48 . 516 1 . 00 25 .59 C
ATOM 278 CG2 VAL A 40 10 .696 16 . 792 47 . 849 1 . 00 22 .78 C
ATOM 279 N CYS A 41 7 .544 16 .439 46 . 999 1 . 00 21 .28 N
ATOM 280 CA CYS A 41 6 .320 15 . 924 47 . 602 1 . 00 21 . 02 C
ATOM 281 C CYS A 41 6 .492 15 . 615 49 . 086 1 . 00 22 .19 C
ATOM 282 O CYS A 41 7 .594 15 . 672 49 . 592 1 . 00 22 . 06 O
ATOM 283 CE CYS A 41 5 .765 14 . 726 46 . 798 1 . 00 23 .58 C
ATOM 284 SG CYS A 41 6 .793 13 .258 46 . 916 1 . 00 29 . 99 S
ATOM 285 N LYS A 42 5 .377 15 . 324 49 . 769 1 . 00 22 . 93 N
ATOM 286 CA LYS A 42 5 .321 15 . 197 51 .218 1 . 00 24 .21 C
ATOM 287 C LYS A 42 6 .323 14 . 172 51 . 746 1 . 00 25 .17 C
ATOM 288 O LYS A 42 7 . 081 14 .466 52 . 647 1 . 00 28 .10 O
ATOM 289 CE LYS A 42 3 .895 14 . 818 51 . 654 1 . 00 27 .31 C
ATOM 290 N GLY A 43 6 .315 12 . 979 51 . 155 1 . 00 26 .77 N
ATOM 291 CA GLY A 43 7 .159 11 . 889 51 . 590 1 . 00 23 .53 C
ATOM 292 C GLY A 43 8 .637 12 . 007 51 .284 1 . 00 20 .79 C
ATOM 293 O GLY A 43 9 .429 11 .333 51 . 913 1 . 00 21 .17 O
ATOM 294 N SER A 44 8 . 992 12 . 821 50 .289 1 . 00 20 .86 N
ATOM 295 CA SER A 44 10 .357 13 . 019 49 . 848 1 . 00 17 .41 C
ATOM 296 C SER A 44 11 . 005 14 .283 50 .408 1 . 00 19 .57 C
ATOM 297 O SER A 44 12 .198 14 .456 50 .257 1 . 00 20 .41 O
ATOM 298 CB SER A 44 10 .441 13 . 004 48 . 304 1 . 00 16 .66 C
ATOM 299 OG SER A 44 10 .203 11 . 699 47 . 807 1 . 00 28 .33 O
ATOM 300 N ARG A 45 10 .210 15 . 156 51 . 048 1 . 00 23 .59 N
ATOM 301 CA ARG A 45 10 .724 16 .343 51 . 729 1 . 00 26 .23 C
ATOM 302 C ARG A 45 11 .855 15 . 974 52 . 676 1 . 00 26 .13 C
ATOM 303 O ARG A 45 11 .700 15 . 116 53 . 535 1 . 00 28 .18 O
ATOM 304 CE ARG A 45 9 .612 17 . 075 52 .483 1 . 00 27 .27 C
ATOM 305 CG ARG A 45 1O . 068 18 .324 53 . 189 1 . 00 41 .68 C
ATOM 306 CD ARG A 45 8 .898 19 . 083 53 . 784 1 . 00 50 . 91 C
ATOM 307 NE ARG A 45 8 .524 18 . 645 55 . 132 1 . 00 58 .75 N
ATOM 308 CZ ARG A 45 7 .585 17 . 741 55 .410 1 . 00 66 .28 C
ATOM 309 NH1 ARG A 45 6 . 904 17 . 139 54 .439 1 . 00 70 .34 N
ATOM 310 NH2 ARG A 45 7 .326 17 .432 56 . 674 1 . 00 71 .55 N
ATOM 311 N GLY A 46 13 . 008 16 . 600 52 .472 1 . 00 3O .17 N
ATOM 312 CA GLY A 46 14 .193 16 .327 53 .284 1 . 00 30 .83 C
ATOM 313 C GLY A 46 14 . 991 15 . 101 52 . 881 1 . 00 29 .13 C
ATOM 314 O GLY A 46 16 . 055 14 . 879 53 .423 1 . 00 3O .41 O
ATOM 315 N VAL A 47 14 .483 14 .299 51 . 937 1 . 00 26 . 03 N
ATOM 316 CA VAL A 47 15 .181 13 . 108 51 .476 1 . 00 24 .45 C
ATOM 317 C VAL A 47 15 .893 13 .387 50 . 148 1 . 00 23 . 06 C
ATOM 318 O VAL A 47 16 . 977 12 . 875 49 . 871 1 . O0 23 .63 O
ATOM 319 CE VAL A 47 14 .196 11 . 876 51 .309 1 . 00 23 . 02 C
ATOM 320 CG1 VAL A 47 14 . 965 10 . 609 50 . 976 1 . 00 26 . 99 C
ATOM 321 CG2 VAL A 47 13 .361 11 . 669 52 . 569 1 . 00 31 .77 C
ATOM 322 N VAL A 48 15 .254 14 . 179 49 .307 1 . 00 19 .51 N
ATOM 323 CA VAL A 48 15 .818 14 . 559 48 . 026 1 . 00 21 .30 C
ATOM 324 C VAL A 48 16 . 011 16 . 062 47 . 983 1 . 00 20 . 95 C
ATOM 325 O VAL A 48 15 .381 16 . 796 48 . 761 1 . 00 26 . 92 O
ATOM 326 CE VAL A 48 14 .884 14 . 136 46 . 850 1 . 00 19 .26 C
ATOM 327 CG1 VAL A 48 14 .533 12 . 688 46 . 936 1 . 00 19 .48 C
ATOM 328 CG2 VAL A 48 13 .639 15 . 008 46 . 809 1 . 00 24 . 94 C
ATOM 329 N CYS A 49 16 .852 16 . 520 47 . 067 1 . 00 21 .60 N
Patent Application Publication Mar. 5, 2009 Sheet 7 of 138 US 2009/0062286 A1

Figure 1A-7
Atom Type Residue # X Y Z Occ B Type

ATOM 330 CA CYS A 49 1'7 .115 17 . 928 46 . 916 1 . 00 21 . 15 C

ATOM 331 C CYS A 49 15 .889 18 .669 46 .440 1. 00 23 .55 C
ATOM 332 O CYS A 49 15 .277 18 .263 45 .462 1 . 00 23 . 67 O
ATOM 333 CE CYS A 49 18 .236 18 .155 45 . 918 1. 00 22 .68 C
ATOM 334 SG CYS A 49 18 .537 19.902 45 .551 1. 00 23 .68 S
ATOM 335 N ASP A 50 15 .567 19 .777 47 .110 1 . 00 23 . 14 N
ATOM 336 CA ASP A 50 14 .422 20 .634 46 .739 1 . 00 25 . 65 C
ATOM 337 C ASP A 50 14 .350 20.988 45 .276 1. 00 22 .40 C
ATOM 338 0 ASP A 50 13 .268 21.009 44 .700 1. 00 23 .56 O
ATOM 339 CE ASP A 50 14 .400 21 . 919 47 .540 1 . 00 24 . 16 C
ATOM 340 CG ASP A 50 13 .367 21.905 48 .592 1. 00 22 .00 C
ATOM 341 OD1 ASP A 50 13 .402 20.999 49 .440 1. 00 29.53 0
ATOM 342 0132 ASP A 50 12 .529 22 .825 48 .597 1 . 00 37 . 12 O
ATOM 343 N ARG A 51 15 .522 21 .206 44 .687 1 . 00 20 . 99 N
ATOM 344 CA ARG A 51 15 .653 21.718 43 .359 1. 00 20.33 C
ATOM 345 C ARG A 51 15 .700 20 .557 42 .342 1 . 00 21 .34 C
ATOM 346 O ARG A 51 14 .790 20 .411 41 .517 1 . 00 19 . 67 O
ATOM 347 CB ARG A 51 16 .888 22 .640 43 .300 1. 00 19.15 C
ATOM 348 CG ARG A 51 17 .290 23 .184 41 . 951 1 . 00 26 .42 C
ATOM 349 CD ARG A 51 16 .229 24 .098 41 .384 1. 00 38 .44 C
ATOM 350 NE ARG A 51 16 .601 24 .616 40 . 077 1 . 00 5O . 77 N
ATOM 351 CZ ARG A 51 15 .880 25.499 39 .391 1. 00 56 .60 C
ATOM 352 NH1 ARG A 51 14 .733 25.964 39 .885 1. 00 49.60 N
ATOM 353 NH2 ARG A 51 16 .308 25 . 914 38 .204 1 . 00 59 . 11 N
ATOM 354 N CYS A 52 16 .738 19 .736 42 .427 1 . 00 22 . 51 N
ATOM 355 CA CYS A 52 17 . 015 18 .706 41 .409 1 . 00 24 . 08 C
ATOM 356 C CYS A 52 16 .341 17 .346 41 .679 1 . 00 22 . 17 C
ATOM 357 O CYS A 52 16 .376 16 .474 40 .820 1 . 00 26 . 05 O
ATOM 358 CE CYS A 52 18 .546 18 .546 41 .193 1. 00 22 .43 C
ATOM 359 SG CYS A 52 19 .412 17.699 42 .541 1. 00 26 .51 S
ATOM 360 N LEU A 53 15 .709 17 .199 42 .843 1 . 00 18 .41 N
ATOM 361 CA LEU A 53 14 . 904 16 .048 43 .200 1. 00 18 .83 C
ATOM 362 C LEU A 53 15 .718 14 .745 43 .218 1 . 00 21 . 76 C
ATOM 363 O LEU A 53 15 .156 13 .668 43 .106 1. 00 25.93 0
ATOM 364 CE LEU A 53 13 .640 15 . 930 42 .319 1 . 00 17 . 52 C
ATOM 365 CG LEU A 53 12 .701 17 .145 42 .326 1 . 00 2O . 62 C
ATOM 366 CD1 LEU A 53 11 .543 16 .895 41 .362 1 . 00 2O . 61 C
ATOM 367 CD2 LEU A 53 12 .220 17 .533 43 .735 1 . 00 16 . 89 C
ATOM 368 N LEU A 54 17 . 040 14 .870 43 .399 1 . 00 23 . 61 N
ATOM 369 CA LEU A 54 17 . 939 13 .709 43 .556 1 . 00 25 .31 C
ATOM 370 C LEU A 54 18 .239 13 .499 45 . 020 1. 00 28 .00 C
ATOM 371 O LEU A 54 18 .418 14 .467 45 .757 1 . 00 27 . 74 O
ATOM 372 CE LEU A 54 19 .245 13 . 919 42 .816 1 . 00 24 . 61 C
ATOM 373 CG LEU A 54 19 .199 14 .127 41 .321 1 . 00 24 . 07 C
ATOM 374 CD1 LEU A 54 20 .628 14 .311 40 .862 1 . 00 29 .46 C
ATOM 375 CD2 LEU A 54 18 .493 12 .967 40 .569 1. 00 24 .89 C
ATOM 376 N GLY A 55 18 .299 12 .235 45 .432 1 . 00 30 . 54 N
ATOM 377 CA GLY A 55 18 .519 11.870 46 .826 1. 00 32 .53 C
ATOM 378 C GLY A 55 19 . 994 11 .853 47 .186 1 . 00 34 . 95 C
ATOM 379 O GLY A 55 20 .833 11 .509 46 .368 1 . 00 35 .30 O
ATOM 380 N LYS A 56 20 .304 12 .248 48 .413 1 . 00 39 . 07 N
ATOM 381 CA LYS A 56 21 .684 12 .307 48 .890 1 . 00 43 . 74 C
ATOM 382 C LYS A 56 21 .715 12 . 070 50 .380 1 . 00 48 .45 C
ATOM 383 O LYS A 56 20 .773 12 .445 51 . 092 1 . 00 49 . 96 O
ATOM 384 CE LYS A 56 22 .319 13 .663 48 .589 1 . 00 42 . 59 C
Patent Application Publication Mar. 5, 2009 Sheet 8 of 138 US 2009/0062286 A1

Figure 1A-8
Atom Type Residue # X Y Z 000 B Type

ATOM 385 N GLU A 57 22 . 806 11 .452 50 . 843 1 . 00 52 .31 N

ATOM 386 CA GLU A 5'7 23 . 050 11 .234 52 .273 1 . 00 53 . 52 C
ATOM 387 C GLU A 5'7 23 . 136 12 . 560 53 . 037 1 . 00 53 . 70 C
ATOM 388 O GLU A 57 22 . 663 12 . 649 54 . 173 1 . 00 56 .39 O
ATOM 389 CB GLU A 5'7 24 .325 10 .406 52 .485 1 . 00 53 . 99 C
ATOM 390 N LYS A 58 23 . 721 13 . 582 52 .403 1 . 00 51 .45 N
ATOM 391 CA LYS A 58 23 . 860 14 . 917 53 . 004 1 . 00 48 . 86 C
ATOM 392 C LYS A 58 23 .221 16 . 028 52 . 159 1 . 00 44 .44 C
ATOM 393 O LYS A 58 23 . 699 16 .376 51 . 079 1 . 00 45 . 83 O
ATOM 394 CB LYS A 58 25 .336 15 .244 53 .276 1 . 00 49 . 50 C
ATOM 395 N LEU A 59 22 . 128 16 . 576 52 . 663 1 . 00 40 . 96 N
ATOM 396 CA LEU A 59 21 . 530 17 . 763 52 . 075 1 . 00 35 .31 C
ATOM 397 C LEU A 59 21 . 719 18 . 911 53 . 060 1 . 00 36 .33 C
ATOM 398 O LEU A 59 21 . 591 18 . 706 54 .273 1 . 00 33 .46 O
ATOM 399 CB LEU A 59 20 . 031 17 . 540 51 . 857 1 . 00 37 . 68 C
ATOM 400 CG LEU A 59 19 . 569 16 .425 50 . 905 1 . 00 32 .26 C
ATOM 401 CD1 LEU A 59 18 . 101 16 . 179 51 . 079 1 . 00 33 . 15 C
ATOM 402 CD2 LEU A 59 19 . 905 16 . 749 49 .474 1 . 00 30 .38 C
ATOM 403 N MET A 60 21 . 993 20 . 102 52 . 536 1 . 00 37 . 62 N
ATOM 404 CA MET A 60 22 . 127 21 .329 53 .338 1 . 00 41 . 65 C
ATOM 405 C MET A 60 20 . 816 22 . 140 53 .441 1 . 00 38 . 05 C
ATOM 406 O MET A 60 20 .276 22 . 596 52 .445 1 . 00 35 . 80 O
ATOM 407 CB MET A 60 23 .243 22 .205 52 . 767 1 . 00 41 . 15 C
ATOM 408 CG MET A 60 22 . 985 22 . 681 51 .335 1 . 00 47 .31 C
ATOM 409 SD MET A 60 24 .436 23 .248 50 .428 1 . 00 57 .41 S
ATOM 410 CE MET A 60 24 . 805 24 . 790 51 .277 1 . 00 66 . 64 C
ATOM 411 N ARG A 61 20 .326 22 .323 54 . 662 1 . 00 37 .41 N
ATOM 412 CA ARG A 61 19 . 108 23 . 084 54 . 909 1 . 00 34 . 91 C
ATOM 413 C ARG A 61 19 .280 24 . 576 54 . 583 1 . 00 34 . 87 C
ATOM 414 O ARG A 61 2O . 391 25 . 115 54 . 643 1 . 0O 34 . 13 O
ATOM 415 CB ARG A 61 18 . 652 22 . 892 56 . 357 1 . 0O 36 . 33 C
ATOM 416 N CYS A 62 18 . 187 25 .226 54 . 184 1 . 0O 3O . 34 N
ATOM 417 CA CYS A 62 18 . 171 26 . 673 54 . 037 1 . 0O 3O . 05 C
ATOM 418 C CYS A 62 18 .273 27 .297 55 .429 1 . 00 28 . 88 C
ATOM 419 O CYS A 62 17 . 538 26 . 920 56 .326 1 . 00 27 .28 O
ATOM 420 CB CYS A 62 16 . 872 27 . 140 53 .364 1 . 00 30 . 87 C
ATOM 421 SG CYS A 62 16 . 564 28 . 948 53 .408 1 . 00 28 . 57 S
ATOM 422 N SER A 63 19 . 169 28 .263 55 . 585 1 . 00 31 .36 N
ATOM 423 CA SER A 63 19 .431 28 . 905 56 . 891 1 . 00 32 .41 C
ATOM 424 C SER A 63 18 .243 29 . 641 57 .492 1 . 00 31 . 82 C
ATOM 425 O SER A 63 18 . 069 29 . 679 58 . 725 1 . 00 30 .48 O
ATOM 426 CB SER A 63 20 . 576 29 . 896 56 . 743 1 . 00 33 . 96 C
ATOM 427 OG SER A 63 21 . 793 29 . 190 56 . 601 1 . 00 44 . 87 O
ATOM 428 N GLN A 64 17 .448 30 .243 56 . 611 1 . 00 29 . 83 N
ATOM 429 CA GLN A 64 16 .355 31 . 105 57 . 001 1 . 00 29 . 16 C
ATOM 430 C GLN A 64 15 . 118 30 .339 57 .461 1 . 00 30 . 79 C
ATOM 431 O GLN A 64 14 . 533 30 . 691 58 .481 1 . 00 32 . 88 O
ATOM 432 CB GLN A 64 16 . 026 32 . 089 55 . 875 1 . 00 28 . 01 C
ATOM 433 CG GLN A 64 17 .236 32 . 664 55 . 153 1 . 00 37 . 99 C
ATOM 434 CD GLN A 64 18 . 185 33 .399 56 . 081 1 . 00 54 .23 C
ATOM 435 OE1 GLN A 64 17 . 765 34 .236 56 . 885 1 . 00 61 . 69 O
ATOM 436 NE2 GLN A 64 19 .477 33 . 090 55 . 974 1 . 00 60 .24 N
ATOM 437 N CYS A 65 14 . 714 29 .284 56 . 742 1 . 00 31 . 93 N
ATOM 438 CA CYS A 65 13 . 548 28 .485 57 . 179 1 . 00 29 .22 C
ATOM 439 C CYS A 65 13 . 886 27 . 136 57 . 820 1 . 00 31 . 62 C
Patent Application Publication Mar. 5, 2009 Sheet 9 of 138 US 2009/0062286 A1

518%
Atom Type Residue # X Y Z Occ E Type

ATOM 440 O CYS A 65 13 .086 26 .613 58 .594 1.00 30 .20 O

ATOM 441 CB CYS A 65 12 . 570 28 .244 56 . 026 1 . 00 30 . 06 C
ATOM 442 SC CYS A 65 13 .353 27 .406 54 . 648 1 . 00 27 .49 S
ATOM 443 N ARG A 66 15 . 058 26 . 592 57 .491 1 . 00 28 . 55 N
ATOM 444 CA ARG A 66 15 .453 25 .239 57 . 865 1 . 00 33 .29 C
ATOM 445 C ARG A 66 14 .478 24 . 157 57 .362 1 . 00 31 .22 C
ATOM 446 O ARG A 66 14 .406 23 . 086 57 . 936 1 . 00 34 .32 O
ATOM 447 CB ARG A 66 15.664 25 .123 59 .387 1.00 33 . 98 C
ATOM 448 CG ARG A 66 16 .215 26 .383 60 . 001 1 . 0O 38 . 09 C
ATOM 449 CD ARG A 66 17 .305 26 . 124 60 . 964 1 . 00 43 . 19 C
ATOM 450 NE ARG A 66 18 .347 27 . 131 60 . 812 1 . 00 38 . 59 N
ATOM 451 CZ ARG A 66 19 .374 27 .253 61 . 641 1 . 00 39 . 68 C
ATOM 452 NH1 ARG A 66 19.476 26 .433 62 .670 1.00 36 .52 N
ATOM 453 NH2 ARG A 66 20 .289 28 . 188 61 .440 1 . 0O 43 .46 N
ATOM 454 N VAL A 67 13 . 751 24 .454 56 .293 1 . O0 30 .23 N
ATOM 455 CA VAL A 67 12 .760 23 .537 55 .710 1.00 30 .60 C
ATOM 456 C VAL A 67 13 .215 23 . 073 54 .310 1 . 00 30 .37 C
ATOM 457 O VAL A 67 13 .309 21 . 877 54 . 059 1 . 00 33 .39 O
ATOM 458 CB VAL A 67 11 .306 24 . 166 55 . 684 1 . 00 31 . 53 C
ATOM 459 CG1 VAL A 67 10 . 300 23 .208 55 . 019 1 . 00 26 . 64 C
ATOM 460 CG2 VAL A 67 10 . 832 24 . 523 57 . 111 1 . 00 24 . 55 C
ATOM 461 N ALA A 68 13 . 500 24 . 011 53 .413 1 . 00 27 . 14 N
ATOM 462 CA ALA A 68 14 . 075 23 . 688 52 . 110 1 . 00 25 . 99 C
ATOM 463 C ALA A 68 15.471 23 .076 52 .287 1.00 27 .72 C
ATOM 464 O ALA A 68 16 .296 23 . 593 53 . 040 1 . 00 29 . 70 O
ATOM 465 CB ALA A 68 14 . 158 24 . 927 51 .228 1 . 00 27 .21 C
ATOM 466 N LYS A 69 15 . 724 21 . 965 51 . 605 1 . 00 25 . 10 N
ATOM 467 CA LYS A 69 17 . 035 21 .331 51 . 656 1 . 00 25 .32 C
ATOM 468 C LYS A 69 17 . 604 21 . 136 50 .256 1 . 00 25 . 74 C
ATOM 469 O LYS A 69 16 . 872 20 . 903 49 . 303 1 . 00 23 . 33 O
ATOM 470 CB LYS A 69 16 .987 20 .009 52 .406 1.00 25 .11 C
ATOM 471 CG LYS A 69 16 . 539 20 . 096 53 . 834 1 . 0O 28 . 80 C
ATOM 472 CD LYS A 69 16 . 920 18 . 823 54 . 565 1 . 00 40 . 10 C
ATOM 473 CE LYS A 69 15.990 18 .523 55 .738 1.00 47 .38 C
ATOM 474 NZ LYS A 69 15 . 720 19 . 705 56 . 596 1 . 00 54 .24 N
ATOM 475 N TYR A 70 18 . 921 21 .246 50 . 141 1 . O0 26 . 53 N
ATOM 476 CA TYR A 70 19 . 594 21 . 184 48 . 855 1 . 00 26 . 14 C
ATOM 477 C TYR A 70 2O . 801 20 .274 48 . 922 1 . O0 29 .41 C
ATOM 478 O TYR A 70 21.377 20 .098 49 . 984 1.00 28 .37 O
ATOM 479 CB TYR A 70 20.014 22 .587 48 .418 1.00 28 .14 C
ATOM 480 CG TYR A 70 18 .861 23 .540 48 .388 1.00 30 .52 C
ATOM 481 CD1 TYR A 70 17.959 23 .542 47 .306 1.00 26 . 08 C
ATOM 482 CE1 TYR A 70 16 . 896 24 .401 47 .280 1 . O0 25 . 13 C
ATOM 483 CZ TYR A 70 16 .701 25 .278 48 .324 1.00 28 .35 C
ATOM 484 OH TYR A 70 15.631 26 .117 48 .298 1.00 24 .15 O
ATOM 485 CB2 TYR A 70 17 . 568 25 .298 49 .411 1 . O0 35 . 10 C
ATOM 486 CD2 TYR A 70 18 .639 24 .420 49 .436 1.00 32 .75 C
ATOM 487 N CYS A 71 21.168 19 .705 47 .774 1.00 31 .79 N
ATOM 488 CA CYS A 71 22 .349 18 . 864 47 . 648 1 . 00 32 . 55 C
ATOM 489 C CYS A 71 23 . 633 19 . 690 47 .453 1 . 00 33 . 54 C
ATOM 490 O CYS A 71 24 . 731 19 . 174 47 . 620 1 . 00 35 . 52 O
ATOM 491 CE CYS A 71 22 . 191 17 . 949 46 .439 1 . 00 30 . 51 C
ATOM 492 SG CYS A 71 22 .287 18 . 846 44 . 889 1 . 00 30 . 89 S
ATOM 493 N SER A 72 23 .487 20 . 950 47 . 052 1 . 00 35 .18 N
ATOM 494 CA SER A 72 24 .620 21 .746 46 .630 1 . 00 36 . 00 C
Patent Application Publication Mar. 5, 2009 Sheet 10 of 138 US 2009/0062286 A1

Figure 1A- 1 0
Atom Type Residue # X Y Z 000 B Type

ATOM 495 C SER A 72 24 .317 23 .232 46 .730 1 . 00 38 . 64 C

ATOM 496 O SER A 72 23 . 153 23 . 641 46 .700 1 . 00 38 . 01 O
ATOM 497 CE SER A 72 24 . 964 21 .407 45 .186 1 . O0 36 .24 C
ATOM 498 OG SER A 72 23 . 928 21 . 803 44 .317 1 . O0 32 . 75 O
ATOM 499 N ALA A 73 25 .372 24 . 039 46 .833 1 . O0 41 . 08 N
ATOM 500 CA ALA A 73 25 .246 25 . 500 46 .751 1 . O0 41 . 56 C
ATOM 501 C ALA A 73 24 . 597 25 . 932 45 .436 1 . O0 40 . 94 C
ATOM 502 O ALA A 73 23 . 813 26 . 878 45 .407 1 . O0 42 . 06 O
ATOM 503 CB ALA A 73 26 . 624 26 . 171 46 . 920 1 . 0O 42 .24 C
ATOM 504 N LYS A 74 24 . 933 25 .237 44 .349 1 . 00 40 . 53 N
ATOM 505 CA LYS A 74 24 .375 25 . 537 43 . 028 1 . 0O 38 .37 C
ATOM 506 C LYS A 74 22 . 849 25 . 392 43 . 021 1 . 00 34 . 84 C
ATOM 507 O LYS A 74 22 . 139 26 .268 42 .507 1 . 00 32 .26 O
ATOM 508 CE LYS A 74 25 . 002 24 . 641 41 . 948 1 . O0 40 .24 C
ATOM 509 N CYS A 75 22 .356 24 .299 43 .602 1 . O0 33 .42 N
ATOM 510 CA CYS A 75 2O . 914 24 . 054 43 .666 1 . O0 30 .26 C
ATOM 511 C CYS A 75 20 .236 25 . 097 44 .564 1 . O0 30 . 95 C
ATOM 512 O CYS A 75 19 .204 25 . 629 44 .197 1 . O0 29 . 63 O
ATOM 513 CB CYS A 75 20 . 586 22 . 604 44 . 085 1 . 00 31 .25 C
ATOM 514 SG CYS A 75 20 . 641 21 .323 42 .735 1 . 0O 28 . 01 S
ATOM 515 N GLN A 76 2O . 846 25 .420 45 .710 1 . 00 33 . 54 N
ATOM 516 CA GLN A 76 20 . 302 26 .447 46 .607 1 . 00 34 . 88 C
ATOM 517 C GLN A 76 2O . 089 27 . 779 45 .891 1 . O0 33 . 13 C
ATOM 518 O GLN A 76 19 . 041 28 .408 46 . 038 1 . O0 30 . 66 O
ATOM 519 CE GLN A 76 21 . 183 26 . 629 47 .847 1 . O0 34 .23 C
ATOM 520 CG GLN A 76 2O . 528 27 .479 48 . 934 1 . O0 37 . 94 C
ATOM 521 CD GLN A 76 21 .205 27 .349 50 .300 1 . O0 41 . 19 C
ATOM 522 0E1 GLN A 76 22 .289 26 . 769 50 .425 1 . O0 51 . 68 O
ATOM 523 NE2 GLN A 76 2O . 559 27 . 890 51 .329 1 . 0O 44 .48 N
ATOM 524 N LYS A 77 21 . 080 28 . 184 45 . 097 1 . 00 33 . 14 N
ATOM 525 CA LYS A 77 21 . 040 29 .452 44 .391 1 . 00 33 .42 C
ATOM 526 C LYS A 77 2O . 010 29 .465 43 .265 1 . O0 33 .35 C
ATOM 527 O LYS A 77 19 .236 30 .405 43 .132 1 . O0 33 .38 O
ATOM 528 CE LYS A 77 22 .433 29 . 788 43 .833 1 . O0 36 . 78 C
ATOM 529 N LYS A 78 19 . 997 28 .404 42 .472 1 . O0 30 . 94 N
ATOM 530 CA LYS A 78 19 . 074 28 .279 41 .351 1 . O0 31 . 78 C
ATOM 531 C LYS A 78 17 . 631 28 .208 41 .833 1 . O0 29 .28 C
ATOM 532 O LYS A 78 16 . 707 28 . 598 41 .128 1 . 00 30 .47 O
ATOM 533 CE LYS A 78 19 .424 27 . 025 40 .547 1 . 00 32 . 10 C
ATOM 534 N ALA A 79 17 .446 27 . 695 43 . 045 1 . 00 29 . 09 N
ATOM 535 CA ALA A 79 16 . 122 27 . 544 43 .615 1 . O0 26 . 05 C
ATOM 536 C ALA A 79 15 . 632 28 . 826 44 .290 1 . O0 25 . 91 C
ATOM 537 O ALA A 79 14 .454 28 . 946 44 .594 1 . O0 24 . 71 O
ATOM 538 CE ALA A 79 16 . 116 26 .426 44 .578 1 . O0 26 . 66 C
ATOM 539 N TRP A 80 16 . 528 29 . 782 44 .521 1 . O0 28 .47 N
ATOM 540 CA TRP A 80 16 . 147 30 . 983 45 .277 1 . O0 28 . 02 C
ATOM 541 C TRP A 80 14 . 962 31 . 779 44 .707 1 . 00 26 . 77 C
ATOM 542 O TRP A 80 14 . 071 32 . 137 45 .466 1 . 0O 30 . 64 O
ATOM 543 CE TRP A 80 17 . 349 31 . 885 45 .604 1 . 00 30 . 72 C
ATOM 544 CG TRP A 80 16 . 950 33 . 109 46 .394 1 . O0 32 . 88 C
ATOM 545 CD1 TRP A 80 16 . 916 34 .397 45 . 937 1 . O0 32 . 64 C
ATOM 546 NEl TRP A 80 16 .475 35 .239 46 . 934 1 . O0 29 . 88 N
ATOM 547 CE2 TRP A 80 16 .207 34 . 507 48 . 055 1 . O0 29 .41 C
ATOM 548 CD2 TRP A 80 16 .489 33 . 156 47 .757 1 . O0 25 . 14 C
ATOM 549 CE3 TRP A 80 16 .291 32 . 196 48 .747 1 . O0 28 .30 C
Patent Application Publication Mar. 5, 2009 Sheet 11 of 138 US 2009/0062286 A1

Figure lA-l 1
Atom Type Residue # X Y Z Occ E Type

ATOM 550 CZ3 TRP A 80 15 .815 32 .605 49 . 997 1 . 00 31 .84 C

ATOM 551 CH2 TRP A 80 15 . 550 33 . 951 50 .263 1 . 00 36 . 03 C
ATOM 552 CZ2 TRP A 80 15 . 741 34 . 918 49 .309 1 . 00 35 .20 C
ATOM 553 N PRO A 81 14 . 909 32 . 023 43 .379 1 . 00 27 . 86 N
ATOM 554 CA PRO A 81 13 .716 32 .655 42 .822 1 . 00 28 .53 C
ATOM 555 C PRO A 81 12 .387 31 . 981 43 .172 1 . 00 27 .10 C
ATOM 556 0 PRO A 81 11 . 391 32 . 679 43 . 344 1 . 00 28 . 87 O
ATOM 557 CB PRO A 81 13 . 955 32 .558 41 .308 1 . 00 31 .50 C
ATOM 558 CG PRO A 81 15 .418 32 .498 41 . 175 1 . 00 29 .26 C
ATOM 559 CD PRO A 81 15 . 902 31 .739 42 .328 1 . 00 27 .88 C
ATOM 560 N ASP A 82 12 .373 30 .648 43 .254 1 . 00 28 . 07 N
ATOM 561 CA ASP A 82 11 . 177 29 . 867 43 . 578 1 . OO 26 . 95 C
ATOM 562 C ASP A 82 11 . 001 29 . 771 45 . 081 1 . 00 24 . 78 C
ATOM 563 O ASP A 82 9 . 913 29 . 541 45 . 573 1 . 00 25 .42 O
ATOM 564 CB ASP A 82 11 .303 28 .420 43 . 053 1 . 00 31 . 71 C
ATOM 565 CG ASP A 82 11 .199 28 .309 41 .531 1 . 00 36 . 09 C
ATOM 566 ODl ASP A 82 11 . 146 29 .343 40 . 820 1 . O0 32 .44 O
ATOM 567 OD2 ASP A 82 11 . 198 27 . 155 41 . 052 1 . 00 31 . 72 O
ATOM 568 N HIS A 83 12 . 097 29 . 889 45 . 813 1 . 00 25 . 62 N
ATOM 569 CA HIS A 83 12 . 033 29 . 746 47 .253 1 . 00 23 . 97 C
ATOM 570 C HIS A 83 11 .836 31 . 065 47 . 997 1 . 00 23 .71 C
ATOM 571 O HTS A 83 11 .281 31 . 084 49 . 087 1 . 00 24 .21 O
ATOM 572 CB HIS A 83 13 .271 28 . 995 47 . 758 1 . 00 25 .22 C
ATOM 573 CG HIS A 83 13 .229 28 .699 49 .216 1 . 00 21 .18 C
ATOM 574 ND1 HIS A 83 12 .235 2'7 . 945 49 . '783 1 . O0 20 . '78 N
ATOM 575 CEl HTS A 83 12 .432 27 .863 51 . 087 1 . 00 25 .89 C
ATOM 576 NE2 HTS A 83 13 . 509 28 . 561 51 .387 1 . 00 21 . 77 N
ATOM 577 CD2 HIS A 83 14 . 019 29 . 114 50 .238 1 . 00 25 .46 C
ATOM 578 N LYS A 84 12 .249 32 . 164 47 .376 1 . 0O 24 .36 N
ATOM 579 CA LYS A 84 12 .316 33 .499 48 . 022 1 . 00 26 . 93 C
ATOM 580 C LYS A 84 11 . 041 33 .874 48 .803 1 . 00 25 . 90 C
ATOM 581 O LYS A 84 11 . 107 34 .208 49 . 985 1 . 00 25 . 74 O
ATOM 582 CB LYS A 84 12 . 677 34 . 552 46 . 965 1 . 00 23 . 77 C
ATOM 583 CG LYS A 84 12 . 871 35 . 957 47 .488 1 . 00 38 . 09 C
ATOM 584 N ARG A 85 9 . 890 33 . 747 48 . 145 1 . O0 25 . 81 N
ATOM 585 CA ARG A 85 8 . 594 34 . 114 48 . 704 1 . 00 28 .32 C
ATOM 586 C ARG A 85 7 . 914 33 . 042 49 . 567 1 . 00 32 . 15 C
ATOM 587 O ARG A 85 6 . 963 33 .357 50 .290 1 . 00 37 .42 O
ATOM 588 CB ARG A 85 7 . 623 34 . 573 47 . 601 1 . 00 30 . 19 C
ATOM 589 CG ARG A 85 8 . 117 35 . 696 46 . 673 1 . 00 29 . 94 C
ATOM 590 CD ARG A 85 8 .412 36 . 982 47 .367 1 . 00 35 .23 C
ATOM 591 NE ARG A 85 7 .224 37 . 616 47 . 942 1 . 0O 36 .44 N
ATOM 592 CZ ARG A 85 6 .329 38 .308 47 .255 1 . 00 21 . 04 C
ATOM 593 NH1 ARG A 85 6 .474 38 .478 45 . 947 1 . 00 29 . 94 N
ATOM 594 NH2 ARG A 85 5 .297 38 . 874 47 . 885 1 . OO 26 . 77 N
ATOM 595 N GLU A 86 8 .385 31 .792 49 .536 1 . 00 25 .18 N
ATOM 596 CA GLU A 86 7 .838 30 .799 50 .450 1 . 00 24 .16 C
ATOM 597 C GLU A 86 8 .646 30 .552 51 .729 1 . 00 22 .46 C
ATOM 598 O GLU A 86 8 .138 29 . 969 52 .666 1 . 00 22 . 91 O
ATOM 599 CB GLU A 86 7 .662 29 .438 49 .731 1 . 00 27 .28 C
ATOM 600 CG GLU A 86 8 . 965 28 .879 49 .180 1 . 00 26 .37 C
ATOM 601 CD GLU A 86 8 . 908 27 .418 48 .766 1 . 00 21 .17 C
ATOM 602 0E1 GLU A 86 7 .812 26 .884 48 .459 1 . O0 22 .83 O
ATOM 603 0E2 GLU A 86 9 . 985 26 .796 48 .746 1 . 00 25 . 03 O
ATOM 604 N CYS A 87 9 . 919 30 . 932 51 .711 1 . 00 23 .24 N
Patent Application Publication Mar. 5, 2009 Sheet 12 of 138 US 2009/0062286 A1

Figure 1A-12
Atom Type Residue X Y Z Occ E Type

ATOM 605 CA CYS A 87 10 . 815 30 . 796 52 . 843 1 . 00 21 . 57 C

ATOM 606 C CYS A 87 10 . 186 31 . 166 54 .224 1 . O0 23 .33 C
ATOM 607 O CYS A 87 10 . 167 30 . 339 55 . 147 1 . 00 26 . 98 O
ATOM 608 CE CYS A 87 12 . 099 31 . 574 52 . 563 1 . O0 20 .23 C
ATOM 609 SG CYS A 87 13 .382 31 .250 53 . 798 1 . 00 25 . 64 S
ATOM 610 N LYS A 88 9 . 671 32 .391 54 .336 1 . O0 26 . 97 N
ATOM 611 CA LYS A 88 9 . 086 32 . 907 55 . 567 1 . 00 26 .25 C
ATOM 612 C LYS A 88 7 . 818 32 . 177 55 . 981 1 . O0 25 . 53 C
ATOM 613 O LYS A 88 7 . 562 32 . 005 57 . 179 1 . 00 26 . 05 O
ATOM 614 CE LYS A 88 8 . 780 34 .393 55 .419 1 . 00 26 . 86 C
ATOM 615 CG LYS A 88 9 . 989 35 .288 55 .451 1 . O0 39 . 68 C
ATOM 616 CD LYS A 88 9 . 554 36 . 751 55 .483 1 . 00 48 . 13 C
ATOM 617 CE LYS A 88 10 . 726 37 . 674 55 . 795 1 . O0 53 .47 C
ATOM 618 NZ LYS A 88 11 . 519 37 . 994 54 . 573 1 . O0 57 . 75 N
ATOM 619 N CYS A 89 7 . 033 31 . 749 54 . 993 1 . 00 26 .25 N
ATOM 620 CA CYS A 89 5 . 791 30 . 962 55 .233 1 . 00 28 . 02 C
ATOM 621 C CYS A 89 6 . 029 29 . 551 55 . 776 1 . O0 25 . 93 C
ATOM 622 O CYS A 89 5 . 358 29 . 119 56 . 706 1 . 00 29 . 33 O
ATOM 623 CE CYS A 89 4 . 950 30 . 853 53 . 974 1 . O0 24 .21 C
ATOM 624 SG CYS A 89 4 . 686 32 .324 53 . 094 1 . O0 31 .31 S
ATOM 625 N LEU A 90 6 . 994 28 . 858 55 . 183 1 . 00 25 . 95 N
ATOM 626 CA LEU A 90 7 .466 27 . 575 55 . 654 1 . 00 25 . 13 C
ATOM 627 C LEU A 90 8 . 015 27 . 677 57 . 073 1 . O0 26 90 C
ATOM 628 O LEU A 90 7 . 679 26 . 874 57 . 932 1 . O0 30 . 04 O
ATOM 629 CE LEU A 90 8 . 532 27 . 010 54 . 711 1 . O0 24 . 96 C
ATOM 630 CG LEU A 90 8 . 056 26 .481 53 . 343 1 . 00 20 . 74 C
ATOM 631 CD1 LEU A 90 9 .231 26 . 185 52 .449 1 . O0 27 . 73 C
ATOM 632 CD2 LEU A 90 7 . 143 25 .267 53 .486 1 . 00 23 . 66 C
ATOM 633 N LYS A 91 8 . 841 28 . 694 57 .296 1 . 00 31 . 96 N
ATOM 634 CA LYS A 91 9 .447 28 . 965 58 . 602 1 . 00 33 . 77 C
ATOM 635 C LYS A 91 8 .420 29 . 120 59 . 717 1 . O0 36 .28 C
ATOM 636 O LYS A 91 8 . 576 28 . 528 60 . 779 1 . 00 37 . 33 O
ATOM 637 CE LYS A 91 10 .314 30 .215 58 . 538 1 . O0 31 . 75 C
ATOM 638 CG LYS A 91 11 .289 30 .326 59 . 719 1 . O0 35 . 55 C
ATOM 639 CD LYS A 91 11 .423 31 . 738 60 .228 1 . 00 26 . 50 C
ATOM 640 CE LYS A 91 12 .240 32 . 608 59 .317 1 . 00 37 .26 C
ATOM 641 NZ LYS A 91 12 . 074 34 . 059 59 . 643 1 . O0 29 . 08 N
ATOM 642 N SER A 92 7 .380 29 . 907 59 .472 1 . 00 39 . 09 N
ATOM 643 CA SER A 92 6 .431 30 .234 60 . 526 1 . O0 45 . 09 C
ATOM 644 C SER A 92 5 . 632 29 . 020 60 . 983 1 . O0 46 . 98 C
ATOM 645 O SER A 92 5 .284 28 . 909 62 . 165 1 . 00 47 . 86 O
ATOM 646 CE SER A 92 5 . 507 31 .379 60 . 109 1 . O0 45 . 66 C
ATOM 647 OG SER A 92 4 . 745 31 . 041 58 . 968 1 . O0 54 28 O
ATOM 648 N CYS A 93 5 .381 28 . 095 60 . 061 1 . O0 46 .22 N
ATOM 649 CA CYS A 93 4 . 556 26 . 943 60 .380 1 . O0 46 . 64 C
ATOM 650 C CYS A 93 5 . 321 25 . 710 60 . 897 1 . 00 46 . 67 C
ATOM 651 O CYS A 93 4 . 696 24 . 807 61 .444 1 . O0 49 . 55 O
ATOM 652 CE CYS A 93 3 . 640 26 . 597 59 .205 1 . 00 46 .21 C
ATOM 653 SG CYS A 93 4 .452 25 . 767 57 . 856 1 . 00 47 .22 S
ATOM 654 N LYS A 94 6 . 648 25 . 676 60 . 743 1 . 00 46 .42 N
ATOM 655 CA LYS A 94 7 .471 24 . 557 61 .243 1 . O0 49 .29 C
ATOM 656 C LYS A 94 7 . 176 24 .265 62 . 726 1 . 00 50 . 95 C
ATOM 657 O LYS A 94 7 . 189 25 . 196 63 . 538 1 . 00 53 . 57 O
ATOM 658 CE LYS A 94 8 . 956 24 . 863 61 . 063 1 . O0 47 . 66 C
ATOM 659 CG LYS A 94 9 . 858 23 . 660 61 .285 1 . 00 54 .35 C
Patent Application Publication Mar. 5, 2009 Sheet 13 of 138 US 2009/0062286 A1

Figure 1A-13
Atom Type Residue # X Y Z 000 E Type

ATOM 660 CD LYS A 94 11 .230 24 . 064 61 . 770 1 . 00 62 . 76 C

ATOM 661 CE LYS A 94 12 . 066 24 . 626 60 . 651 1 . 00 64 . 88 C
ATOM 662 NZ LYS A 94 13 . 027 25 . 623 61 . 184 1 . O0 69 .38 N
ATOM 663 N PRO A 95 6 . 913 22 . 984 63 . 096 1 . 00 52 07 N
ATOM 664 CA PRO A 95 7 . 000 21 . 705 62 .356 1 . 00 52 .39 C
ATOM 665 C PRO A 95 5 . 815 21 .362 61 .432 1 . 00 50 . 54 C
ATOM 666 O PRO A 95 5 . 927 20 .422 60 . 638 1 . 00 52 .34 O
ATOM 667 CE PRO A 95 7 . 079 20 . 667 63 .483 1 . 00 53 . 02 C
ATOM 668 CG PRO A 95 6 .225 21 .257 64 . 561 1 . 00 53 . 67 C
ATOM 669 CD PRO A 95 6 .429 22 . 764 64 .477 1 . 00 52 . 56 C
ATOM 670 N ARG A 96 4 . 698 22 . 088 61 . 548 1 . 00 47 .32 N
ATOM 671 CA ARG A 96 3 . 555 21 . 909 60 . 635 1 . 00 43 . 96 C
ATOM 672 C ARG A 96 3 . 943 22 .289 59 .202 1 . 00 40 . 02 C
ATOM 673 O ARG A 96 4 . 845 23 . 093 58 . 992 1 . 00 41 . 75 O
ATOM 674 CE ARG A 96 2 .348 22 . 728 61 . 104 1 . 00 45 28 C
ATOM 675 N TYR A 97 3 .280 21 . 687 58 .224 1 . 00 35 . 10 N
ATOM 676 CA TYR A 97 3 . 701 21 . 780 56 . 829 1 . O0 30 . 17 C
ATOM 677 C TYR A 97 2 .458 21 . 639 55 . 971 1 . 00 25 . 97 C
ATOM 678 O TYR A 97 1 . 624 20 . 788 56 .234 1 . 00 27 . 50 O
ATOM 679 CE TYR A 97 4 . 731 20 . 684 56 . 510 1 . 00 27 97 C
ATOM 680 CG TYR A 97 5 .289 20 . 671 55 . 099 1 . 00 31 . 02 C
ATOM 681 CD1 TYR A 97 6 . 323 21 . 532 54 . 723 1 . 00 34 . 67 C
ATOM 682 CE1 TYR A 97 6 . 846 21 . 513 53 .408 1 . 00 34 .44 C
ATOM 683 CZ TYR A 97 6 .343 20 .601 52 .482 1. O0 21 .43 C
ATOM 684 OH TYR A 97 6 . 836 20 . 576 51 .215 1 . 00 27 . 62 O
ATOM 685 CE2 TYR A 97 5 .325 19 . 715 52 . 839 1 . 00 29 . 93 C
ATOM 686 CD2 TYR A 97 4 . 811 19 . 745 54 . 141 1 . 00 29 . 77 C
ATOM 687 N PRO A 98 2 .314 22 . 502 54 . 949 1 . 00 28 .33 N
ATOM 688 CA PRO A 98 1 . 041 22 . 543 54 .238 1 . 00 25 . 89 C
ATOM 689 C PRO A 98 0 . 923 21 .354 53 .270 1 . 00 23 . 68 C
ATOM 690 O PRO A 98 1 . 932 20 . 725 52 . 973 1 . 00 22 . 52 O
ATOM 691 CE PRO A 98 1 . 125 23 . 858 53 .479 1 . 00 27 . 64 C
ATOM 692 CG PRO A 98 2 . 572 24 . 054 53 .227 1 . 00 31 . 57 C
ATOM 693 CD PRO A 98 3 .295 23 .456 54 .394 1 . 00 24 .40 C
ATOM 694 N PRO A 99 *0 .299 21 . 058 52 . 792 1 . 00 24 . 95 N
ATOM 695 CA PRO A 99 *0 .447 20 . 081 51 . 713 1 . 00 24 . 63 C
ATOM 696 C PRO A 99 0 .381 20 . 500 50 .497 1 . 00 22 .28 C
ATOM 697 0 PRO A 99 0 . 646 21 . 715 50 .289 1 . O0 20 .27 O
ATOM 698 CE PRO A 99 1 . 954 20 . 117 51 .416 1 . 00 26 . 94 C
ATOM 699 CG PRO A 99 *2 . 577 20 . 594 52 . 749 1 . 00 22 . 84 C
ATOM 700 CD PRO A 99 1 . 605 21 . 600 53 .232 1 . 00 23 . 10 C
ATOM 701 N ASP A 100 0 . 788 19 . 512 49 . 699 1 . O0 19 . 60 N
ATOM 702 CA ASP A 100 1 . 651 19 . 753 48 . 535 1 . 00 19 . 37 C
ATOM 703 C ASP A 100 1 . 051 20 . 772 47 . 585 1 . 00 18 . 09 C
ATOM 704 O ASP A 100 1 . 759 21 . 642 47 . 073 1 . 00 19 . 90 O
ATOM 705 CE ASP A 100 1 . 960 18 .460 47 . 739 1 . O0 18 . 95 C
ATOM 706 CG ASP A 100 2 . 836 17 .460 48 . 502 1 . 00 20 . 92 C
ATOM 707 OD1 ASP A 100 3 .419 17 . 788 49 . 543 1 . 00 25 . 81 O
ATOM 708 OD2 ASP A 100 2 . 931 16 .307 48 . 038 1 . 00 24 .27 O
ATOM 709 N SER A 101 *0 .253 20 . 659 47 .361 1 . 00 18 . 76 N
ATOM 710 CA SER A 101 0 . 979 21 . 544 46 .473 1 . 00 18 . 30 C
ATOM 711 C SER A 101 *0 . 894 23 . 030 46 . 891 1 . 00 17 . 04 C
ATOM 712 O SER A 101 *0 . 855 23 . 899 46 . 036 1 . 00 16 . 65 O
ATOM 713 CE SER A 101 2 .446 21 . 065 46 . 346 1 . O0 19 . 19 C
ATOM 714 OG SER A 101 *3 . 140 21 . 161 47 . 5'78 1 . O0 21 .29 O
Patent Application Publication Mar. 5, 2009 Sheet 14 of 138 US 2009/0062286 A1

Figure 1A-14
Atom Type Residue # X Y Z Occ B Type

ATOM 715 N VAL A 102 O . 860 23 . 274 48 .202 1 . 00 1'7 . 83 N

ATOM 716 CA VAL A 102 O . 783 24 . 601 48 . 801 1 . 00 20 . 98 C
ATOM 717 C VAL A 102 0 . 594 25 . 186 48 . 545 1 . 0O 15 . 94 C
ATOM 718 O VAL A 102 O .692 26 .265 48 . 018 1 . 0O 16 .40 O
ATOM 719 CB VAL A 102 *1 . 138 24 . 569 50 .363 1 . 00 21 .41 C
ATOM 720 CG1 VAL A 102 O . 752 25 . 840 51 . 047 1 . 00 17 . 54 C
ATOM 721 CG2 VAL A 102 2 . 609 24 . 281 50 . 565 1 . 00 22 . 54 C
ATOM 722 N ARG A 103 1 . 646 24 . 430 48 . 875 1 . 00 17 . 76 N
ATOM 723 CA ARG A 103 3 . 007 24 . 786 48 . 538 1 . 00 17 . 57 C
ATOM 724 C ARG A 103 3 .202 25 . 019 47 . 028 1 . 00 15 . 66 C
ATOM 725 O ARG A 103 3 . 831 26 . 019 46 . 628 1 . 0O 16 . 10 O
ATOM 726 CB ARG A 103 4 . 046 23 . 786 49 . 109 1 . 00 16 . 76 C
ATOM 727 CG ARG A 103 5 .465 24 . 429 49 . 131 1 . 00 19 . 66 C
ATOM 728 CD ARG A 103 6 . 526 23 . 579 49 . 746 1 . 00 22 . 91 C
ATOM 729 NE ARG A 103 7 . 855 24 . 116 49 .449 1 . 0O 23 .47 N
ATOM 730 CZ ARG A 103 9 . 001 23 .508 49 .784 1 . 0O 15 .35 C
ATOM 731 NH1 ARG A 103 8 . 989 22 . 349 50 .431 1 . 00 28 . 70 N
ATOM 732 NH2 ARG A 103 10 . 167 24 . 063 49 .458 1 . 00 18 .22 N
ATOM 733 N LEU A 104 2 . 615 24 . 142 46 .211 1 . 0O 17 .32 N
ATOM 734 CA LEU A 104 2 . 662 24 . 274 44 . 748 1 . 00 15 . 81 C
ATOM 735 C LEU A 104 2 . 021 25 . 594 44 .277 1 . 00 15 . 75 C
ATOM 736 O LEU A 104 2 . 634 26 . 363 43 . 533 1 . 00 18 . 00 O
ATOM 737 CB LEU A 104 1 . 980 23 . 069 44 . 089 1 . 00 14 . 68 C
ATOM 738 CG LEU A 104 1 . 919 23 . 072 42 .550 1 . 00 18 .33 C
ATOM 739 CD1 LEU A 104 3 .301 23 . 050 41 . 928 1 . 0O 13 . 98 C
ATOM 740 CD2 LEU A 104 1 . 028 21 . 953 42 . 016 1 . 00 20 .24 C
ATOM 741 N LEU A 105 O . 780 25 . 859 44 . 703 1 . 00 18 . 13 N
ATOM 742 CA LEU A 105 0 . 080 27 . 054 44 .264 1 . 0O 17 . 72 C
ATOM 743 C LEU A 105 O .728 28 .327 44 .820 1 . 0O 18 . 92 C
ATOM 744 O LEU A 105 0 . 669 29 . 364 44 . 170 1 . 00 19 . 61 O
ATOM 745 CE LEU A 105 1 .411 27 . 023 44 . 603 1 . 0O 21 . 79 C
ATOM 746 CG LEU A 105 2 .301 26 . 240 43 . 632 1 . 00 23 .42 C
ATOM 747 CD1 LEU A 105 3 . 752 26 . 153 44 . 144 1 . 00 19 .31 C
ATOM 748 CD2 LEU A 105 2 .243 26 . 796 42 .204 1 . 00 21 .48 C
ATOM 749 N GLY A 106 1 .313 28 . 219 46 . 014 1 . 00 18 . 55 N
ATOM 750 CA GLY A 106 2 . 172 29 . 249 46 . 588 1 . 00 21 . 73 C
ATOM 751 C GLY A 106 3 .242 29 .730 45 .630 1 . 0O 19 .84 C
ATOM 752 O GLY A 106 3 .449 30 . 914 45 . 501 1 . 00 23 .26 O
ATOM 753 N ARG A 107 3 . 932 28 . 798 44 . 973 1 . 00 18 .38 N
ATOM 754 CA ARG A 107 4 . 836 29 . 122 43 . 875 1 . 00 19 . 54 C
ATOM 755 C ARG A 107 4 . 160 29 . 671 42 . 614 1 . 0O 19 . 61 C
ATOM 756 O ARG A 107 4 .633 30 .663 42 . 041 1 . 0O 21 .83 O
ATOM 757 CB ARG A 107 5 . 734 27 . 911 43 . 540 1 . 00 19 . 53 C
ATOM 758 CG ARG A 107 6 . 771 27 . 630 44 . 646 1 . 00 24 .29 C
ATOM 759 CD ARG A 107 7 .272 26 . 169 44 . 685 1 . 00 17 . 81 C
ATOM 760 NE ARG A 107 8 .412 26 . 018 45 . 577 1 . 00 21 . 64 N
ATOM 761 CZ ARG A 107 9 . 621 25 . 584 45 .226 1 . 00 21 . 54 C
ATOM 762 NH1 ARG A 107 9 . 889 25 . 184 43 . 976 1 . 00 23 . 19 N
ATOM 763 NH2 ARG A 107 10 . 572 25 . 543 46 . 145 1 . 0O 21 .26 N
ATOM 764 N VAL A 108 3 . 073 29 . 030 42 . 181 1 . 0O 16 . 88 N
ATOM 765 CA VAL A 108 2 .427 29 . 380 40 . 944 1 . 00 19 . 73 C
ATOM 766 C VAL A 108 2 . 054 30 . 878 40 . 886 1 . 00 18 . 78 C
ATOM 767 O VAL A 108 2 .261 31 . 510 39 . 871 1 . 00 19 . 08 O
ATOM 768 CB VAL A 108 1 . 152 28 . 539 40 . 688 1 . 0O 17 . 15 C
ATOM 769 C01 VAL A 108 O .278 29 .166 39 .586 1 . 0O 20 .21 C
Patent Application Publication Mar. 5, 2009 Sheet 15 of 138 US 2009/0062286 A1

Figure 1A-15
Atom Type Residue 2.21: X Y Z 000 B Type

ATOM 770 CG2 VAL A 108 1 .513 27 . 090 40 .328 1 . 00 21

. 53 C
ATOM 771 N VAL A 109 1 .491 31 .402 41 . 971 1 . 00.4021 N
ATOM 772 CA VAL A 109 0 .858 32 .721 41 . 946 1 . 00 20
. 03 C
ATOM 773 C VAL A 109 1 .847 33 .829 41 . 596 1 . 00.4721 C
ATOM 774 O VAL A 109 1 .466 34 .789 40 . 954 1 . 00.3223 O
ATOM 775 CE VAL A 109 0 . 067 33 . 054 43 .281 1 . 00 21 . 17 C
ATOM 776 CG1 VAL A 109 *1 .115 32 .125 43 .478 1 . 00 23 .36 C
ATOM 777 CG2 VAL A 109 O . 931 32 . 995 44 .488 1 . 00 19 .46 C
ATOM 778 N PHE A 110 3 .100 33 .684 42 . 024 1 . 00 21 . 31 N
ATOM 779 CA PHE A 110 4 .142 34 .667 41 . 741 1 . 00 24 . 62 C
ATOM 780 C PHE A 110 4 .744 34 .437 40 .380 1 . 00 21 . 70 C
ATOM 781 O PHE A 110 5 .139 35 .371 39 . 728 1 . 00 18 . 80 O
ATOM 782 CE PHE A 110 5 .218 34 .670 42 . 824 1 . 00 23 . 77 C
ATOM 783 CG PHE A 110 4 .683 34 . 933 44 .209 1 . 00 26 . 92 C
ATOM 784 CD1 PHE A 110 4 .148 36 .166 44 . 547 1 . 00 26 . 74 C
ATOM 785 CE1 PHE A 110 3 .643 36 .399 45 . 816 1 . 00 22 . 06 C
ATOM 786 CZ PHE A 110 3 .693 35 .439 46 . 763 1 . 00 24 . 92 C
ATOM 787 CE2 PHE A 110 4 .224 34 .186 46 .450 1 . 00 26 . 03 C
ATOM 788 CD2 PHE A 110 4 .716 33 . 945 45 . 176 1 . 00 28 .31 C
ATOM 789 N LYS A 111 4 .779 33 .178 39 . 936 1 . 00 18 . 58 N
ATOM 790 CA LYS A 111 5 .176 32 .855 38 . 588 1 . 00 16 . 77 C
ATOM 791 C LYS A 111 4 .303 33 .527 37 . 538 1 . 00 20 . 57 C
ATOM 792 O LYS A 111 4 .793 33 . 999 36 .490 1 . 00 21 . 37 O
ATOM 793 CE LYS A 111 5 .147 31 .308 38 .444 1 . 00 20 . 55 C
ATOM 794 CG LYS A 111 5 .622 30 .821 37 . 153 1 . 00 32 . 00 C
ATOM 795 CD LYS A 111 7 .136 30 .888 37 . 039 1 . 00 40 .49 C
ATOM 796 CE LYS A 111 7 .560 30 .365 35 . 693 1 . 00 36 .34 C
ATOM 797 NZ LYS A 111 8 .830 29 .599 35 . 837 1 . 00 54 . 03 N
ATOM 798 N LEU A 112 2 . 998 33 .564 37 . 811 1 . 00 22 .40 N
ATOM 799 CA LEU A 112 2 . 003 34 .112 36 . 904 1 . 00 19 . 05 C
ATOM 800 C LEU A 112 2 .166 35 .594 36 . 664 1 . 00 22 . 16 C
ATOM 801 O LEU A 112 1 .577 36 .132 35 . 762 1 . 00 22 . 58 O
ATOM 802 CB LEU A 112 0 .606 33 .865 37 .459 1 . 00 19 . 80 C
ATOM 803 CG LEU A 112 O .180 32 .397 37 . 544 1 . 00 17 . 77 C
ATOM 804 CD1 LEU A 112 1 .148 32 .215 38 .265 1 . 00 15 . 02 C
ATOM 805 CD2 LEU A 112 0 .160 31 .837 36 . 119 1 . 00 19 .43 C
ATOM 806 N MET A 113 2 . 937 36 .252 37 . 520 1 . 00 24 . 57 N
ATOM 807 CA MET A 113 3 .160 37 .686 37 .392 1 . 00 24 . 84 C
ATOM 808 C MET A 113 4 .391 38 . 036 36 . 543 1 . 00 27 . 59 C
ATOM 809 O MET A 113 4 .559 39 .183 36 . 153 1 . 00 31 .21 O
ATOM 810 CE MET A 113 3 .290 38 .312 38 . 758 1 . 00 23 . 50 C
ATOM 811 CG MET A 113 2 . 099 38 . 080 39 . 634 1 . 00 21 . 86 C
ATOM 812 SD MET A 113 2 .251 39 .177 41 . 047 1 . 00 33 . 75 S
ATOM 813 CE MET A 113 2 .274 38 . 088 42 .422 1 . 00 22 . 87 C
ATOM 814 N ASP A 114 5 .245 37 . 051 36 .265 1 . 00 32 . 04 N
ATOM 815 CA ASP A 114 6 .380 37 .256 35 .352 1 . 00 33 . 62 C
ATOM 816 C ASP A 114 5 .851 37 .653 33 . 968 1 . 00 34 . 86 C
ATOM 817 0 ASP A 114 4 . 933 37 . 013 33 .434 1 . 00 34 . 85 O
ATOM 818 CE ASP A 114 7 .242 35 . 979 35 .288 1 . 00 34 .26 C
ATOM 819 N GLY A 115 6 .393 38 .738 33 .408 1 . 00 38 .28 N
ATOM 820 CA GLY A 115 5 . 978 39 .223 32 . 086 1 . 00 42 . 91 C
ATOM 821 C GLY A 115 6 .574 38 .454 30 . 912 1 . 00 47 . 13 C
ATOM 822 O GLY A 115 6 . 006 38 .450 29 . 812 1 . 00 48 . 55 O
ATOM 823 N ALA A 116 7 .720 37 .812 31 . 140 1 . 00 49 . 16 N
ATOM 824 CA ALA A 116 8 .317 36 . 903 30 . 151 1 . 00 51 . 77 C
Patent Application Publication Mar. 5, 2009 Sheet 16 of 138 US 2009/0062286 A1

Figure 1A-16
Atom Type Residue :1: X Y Z Occ B Type

ATOM 825 C ALA A 116 '7 .495 35 .602 30 . 059 1 . 00 52 . 5'7 C

ATOM 826 O ALA A 116 7 .306 34 . 922 31 . 074 1 . 00 52 . 77 O
ATOM 827 CB ALA A 116 9 .768 36 .603 30 . 517 1 . 00 51 . 53 C
ATOM 828 N PRO A 117 6 . 975 35 .273 28 . 852 1 . 00 53 .42 N
ATOM 829 CA PRO A 117 6 .168 34 . 042 28 . 666 1 . 00 51 . 95 C
ATOM 830 C PRO A 117 6 . 914 32 .770 29 . 101 1 . 00 48 . 51 C
ATOM 831 O PRO A 117 8 .101 32 .622 28 . 786 1 . 00 49 . 92 O
ATOM 832 CB PRO A 117 5 .894 34 . 016 27 . 153 1 . 00 52 . 09 C
ATOM 833 CG PRO A 117 6 . 031 35 .455 26 . 708 1 . 00 55 . 15 C
ATOM 834 CD PRO A 117 7 . 095 36 . 054 27 . 601 1 . 00 53 . 79 C
ATOM 835 N SER A 118 6 .231 31 .890 29 . 840 1 . 00 43 . 19 N
ATOM 836 CA SER A 118 6 .811 30 .615 30 .275 1 . 00 36 . 15 C
ATOM 837 C SER A 118 6 .765 29 .662 29 . 097 1 . 00 33 . 04 C
ATOM 838 O SER A 118 5 .728 29 .535 28 .443 1 . 00 29 . 97 O
ATOM 839 CB SER A 118 6 . 059 29 . 999 31 .489 1 . 00 37 . 80 C
ATOM 840 OG SER A 118 6 .622 28 .724 31 . 878 1 . 00 28 . 70 O
ATOM 841 N GLU A 119 7 .891 29 . 002 28 . 833 1 . 00 30 . 18 N
ATOM 842 CA GLU A 119 7 . 972 27 . 979 27 . 792 1 . 00 29 . 64 C
ATOM 843 C GLU A 119 6 . 960 26 .857 28 . 065 1 . 00 27 . 75 C
ATOM 844 O GLU A 119 6 .374 26 .289 27 . 128 1 . 00 27 . 57 O
ATOM 845 CE GLU A 119 9 .403 27 .425 27 . 709 1 . 00 30 .41 C
ATOM 846 N SER A 120 6 .726 26 .587 29 .350 1 . 00 23 .46 N
ATOM 847 CA SER A 120 5 .809 25 .519 29 . 782 1 . 00 23 . 56 C
ATOM 848 C SER A 120 4 .368 25 .791 29 .331 1 . 00 22 . 67 C
ATOM 849 O SER A 120 3 .544 24 .889 29 .317 1 . 00 20 .36 O
ATOM 850 CB SER A 120 5 .861 25 .342 31 . 318 1 . 00 24 . 17 C
ATOM 851 OG SER A 120 5 .104 26 .350 31 . 989 1 . 00 21 .37 O
ATOM 852 N GLU A 121 4 . 099 27 . 042 28 . 953 1 . 00 20 . 89 N
ATOM 853 CA GLU A 121 2 .762 27 .505 28 . 578 1 . 00 23 .48 C
ATOM 854 C GLU A 121 2 .621 27 .769 27 . 078 1 . 00 21 .48 C
ATOM 855 O GLU A 121 1 .644 28 .361 26 . 651 1 . 00 23 . 03 O
ATOM 856 CB GLU A 121 2 .376 28 .761 29 .397 1 . 00 23 . 79 C
ATOM 857 CG GLU A 121 2 .241 28 .449 30 . 865 1 . 00 21 . 06 C
ATOM 858 CD GLU A 121 1 .834 29 .645 31 . 706 1 . 00 24 . 11 C
ATOM 859 OE1 GLU A 121 2 .584 30 .632 31 . 751 1 . 00 27 .39 O
ATOM 860 0E2 GLU A 121 0 .785 29 .587 32 .359 1 . 00 24 . 58 O
ATOM 861 N LYS A 122 3 .577 27 .305 26 .280 1 . 00 22 .46 N
ATOM 862 CA LYS A 122 3 .559 27 .572 24 . 843 1 . 00 24 . 97 C
ATOM 863 C LYS A 122 2 .253 27 .143 24 . 178 1 . 00 24 . 17 C
ATOM 864 O LYS A 122 1 .726 27 .871 23 .361 1 . 00 26 .47 O
ATOM 865 CB LYS A 122 4 .747 26 . 922 24 . 131 1 . 00 27 . 76 C
ATOM 866 CG LYS A 122 4 .669 26 . 997 22 . 610 1 . 00 34 . 88 C
ATOM 867 CD LYS A 122 6 . 013 26 .683 21 . 979 1 . 00 48 .36 C
ATOM 868 CE LYS A 122 6 .106 27 .271 20 . 573 1 . 00 56 .22 C
ATOM 869 NZ LYS A 122 7 .521 27 .359 20 . 096 1 . 00 61 . 95 N
ATOM 870 N LEU A 123 1 .727 25 . 970 24 . 540 1 . 00 23 . 63 N
ATOM 871 CA LEU A 123 0 .514 25 .449 23 . 886 1 . 00 22 .31 C
ATOM 872 C LEU A 123 O .779 25 .756 24 . 651 1 . 00 21 . 73 C
ATOM 873 O LEU A 123 *1 .858 25 .799 24 . 068 1 . 00 22 . 71 O
ATOM 874 CB LEU A 123 0 .647 23 . 919 23 . 658 1 . 00 20 . 09 C
ATOM 875 CG LEU A 123 1 . 901 23 .420 22 . 906 1 . 00 22 . 90 C
ATOM 876 CD1 LEU A 123 1 .842 21 . 961 22 . 791 1 . 00 22 .39 C
ATOM 877 CD2 LEU A 123 2 . 010 24 . 032 21 . 529 1 . 00 29 . 95 C
ATOM 878 N TYR A 124 *0 .652 25 . 955 25 . 962 1 . 00 23 . 10 N
ATOM 879 CA TYR A 124 1 .795 26 . 022 26 . 882 1 . 00 21 .45 C
Patent Application Publication Mar. 5, 2009 Sheet 17 of 138 US 2009/0062286 A1

Figure 1A-17
Atom Type Residue # X Y Z Occ B Type

ATOM 880 C TYR A 124 1 .270 26 . 647 28 . 154 1 . 00 2O . 61 C

ATOM 881 O TYR A 124 -O .178 26 .296 28 . 603 1 . 00 22 .45 O
ATOM 882 CE TYR A 124 2 .274 24 . 613 27 .214 1 . 00 20 . 58 C
ATOM 883 CG TYR A 124 3 .768 24 .390 27 .398 1 . 00 21.13 C
ATOM 884 CD1 TYR A 124 4 . 701 24 . 886 26 .467 1 . 00 15 . 03 C
ATOM 885 CE1 TYR A 124 6 . 033 24 . 625 26 . 607 1 . 00 19 . 71 C
ATOM 886 CZ TYR A 124 6 .464 23 . 842 27 . 654 1 . 00 20 . 91 C
ATOM 887 OH TYR A 124 7 . 790 23 . 581 27 . 781 1 . 00 21 . 53 O
ATOM 888 CE2 TYR A 124 5 . 571 23 .325 28 . 592 1 . 00 20 .41 C
ATOM 889 CD2 TYR A 124 4 .231 23 . 591 28 .445 1 . 00 16 .23 C
ATOM 890 N SER A 125 2 . 037 27 . 561 28 . 743 1 . 00 21 . 68 N
ATOM 891 CA SER A 125 1 . 574 28 .314 29 . 900 1 . 00 20 . 51 C
ATOM 892 C SER A 125 2 .226 27 . 833 31 .203 1 . 00 19.46 C
ATOM 893 O SER A 125 3 . 197 27 . 114 31 . 162 1 . 00 17 . 97 O
ATOM 894 CB SER A 125 1 . 864 29 . 802 29 . 692 1 . 00 21.09 C
ATOM 895 CC SER A 125 3 .213 30 . 061 30 . 033 1 . 00 25.40 0
ATOM 896 N PHE A 126 -1 . 720 28 .295 32 .357 1 . 00 20.40 N
ATOM 897 CA PHE A 126 2 .380 28 . 040 33 . 617 1 . 00 20.06 C
ATOM 898 C PHE A 126 *3 .863 28 .399 33 . 521 1 . 00 20.07 C
ATOM 899 O PHE A 126 *4 . 708 27 . 684 34 . 013 1 . 00 18 . 86 O
ATOM 900 CE PHE A 126 *1 . 750 28 . 863 34 . 752 1 . 00 20 .21 C
ATOM 901 CG PHE A 126 *2 .485 28 . 731 36 . 047 1 . 00 18 .49 C
ATOM 902 CD1 PHE A 126 *2 .321 27 . 605 36 . 836 1 . 00 18 .19 C
ATOM 903 CEl PHE A 126 3 .032 27 .464 38 . 032 1 . 00 18 .35 C
ATOM 904 CZ PHE A 126 3 . 940 28 .433 38 .412 1 . 00 17 . 99 C
ATOM 905 CE2 PHE A 126 4 . 156 29 . 538 37 . 602 1 . 00 14 .33 C
ATOM 906 CD2 PHE A 126 3 .437 29 . 694 36 .434 1 . 00 21 . 18 C
ATOM 907 N TYR A 127 4 . 162 29 . 544 32 . 912 1 . 00 18 . 82 N
ATOM 908 CA TYR A 127 5 .532 30 . 021 32 . 858 1 . 00 22 .31 C
ATOM 909 C TYR A 127 6 .445 29 . 190 31 . 942 1 . 00 21 . 62 C
ATOM 910 O TYR A 127 7 . 663 29 . 183 32 . 131 1 . 00 24 .31 O
ATOM 911 CE TYR A 127 5 . 566 31 . 505 32 .478 1 . 00 21 . 66 C
ATOM 912 CG TYR A 127 4 . 945 32 .422 33 . 541 1 . 00 22 . 53 C
ATOM 913 CD1 TYR A 127 5 . 646 32 . 772 34 . 698 1 . 00 22 . 11 C
ATOM 914 CE1 TYR A 127 5 . 074 33 . 588 35 . 666 1 . 00 17.09 C
ATOM 915 CZ TYR A 127 3 . 774 34 . 057 35 .480 1 . 00 18 . 90 C
ATOM 916 OH TYR A 127 3 .163 34 . 881 36 .400 1 . 00 22 .55 O
ATOM 917 CE2 TYR A 127 3 .061 33 . 693 34 .357 1 . 00 21.33 C
ATOM 918 CD2 TYR A 127 3 .650 32 . 888 33 .399 1 . 00 22 .05 C
ATOM 919 N ASP A 128 5 .861 28 . 504 30 . 966 1 . 00 21.77 N
ATOM 920 CA ASP A 128 6 .616 27 . 590 30 . 096 1 . 00 22 .29 C
ATOM 921 C ASP A 128 6 .989 26 .296 30 . 821 1 . 00 21.80 C
ATOM 922 0 ASP A 128 7 . 923 25 . 634 30 .433 1 . 00 21.39 0
ATOM 923 CE ASP A 128 *5 .820 27 .236 28 . 833 1 . 00 23 .51 C
ATOM 924 CG ASP A 128 *5 . 565 28 .432 27 . 911 1 . 00 22 . 85 C
ATOM 925 OD1 ASP A 128 *6 .463 29 .232 27 . 683 1 . 00 25 .64 O
ATOM 926 OD2 ASP A 128 *4 .450 28 . 561 27 .368 1 . 00 21 . 96 O
ATOM 927 N LEU A 129 *6 .259 25 . 936 31 . 875 1 . 00 20 .66 N
ATOM 928 CA LEU A 129 6 .498 24 . 652 32 . 565 1 . 00 21 . 71 C
ATOM 929 C LEU A 129 7 . 950 24 .416 32 . 947 1 . 00 23 . 88 C
ATOM 930 O LEU A 129 8 . 648 25 .319 33 .450 1 . 00 24 . 76 O
ATOM 931 CE LEU A 129 5 . 595 24 . 501 33 . 778 1 . 00 20 . 16 C
ATOM 932 CG LEU A 129 4 . 105 24 .499 33 .466 1 . 00 17 . 55 C
ATOM 933 CD1 LEU A 129 3 .321 24 .371 34 . 759 1 . 00 16 . 72 C
ATOM 934 CD2 LEU A 129 3 . 722 23 .404 32 .411 1 . 00 15 .22 C
Patent Application Publication Mar. 5, 2009 Sheet 18 of 138 US 2009/0062286 A1

Figure 1A-18
Atom Type Residue # X Y Z Occ E Type

ATOM 935 N GLU A 130 *8 .403 23 .202 32 . 661 1 . 00 22 . 34 N

ATOM 936 CA GLU A 130 9 . 751 22 .775 32 . 977 1 . 00 21 . 68 C
ATOM 937 C GLU A 130 9 . 894 22 .651 34 .490 1 . 00 21 . 60 C
ATOM 938 O GLU A 130 9 . 058 22 . 024 35 . 150 1 . 00 22 . 19 O
ATOM 939 CB GLU A 130 9 . 999 21 .408 32 .317 1 . 00 21 . 69 C
ATOM 940 CG GLU A 130 e11 . 381 20 .801 32 . 627 1 . 00 27 .24 C
ATOM 941 CD GLU A 130 12 . 512 21 .659 32 . 090 1 . 00 27 . 99 C
ATOM 942 0E1 GLU A 130 12 . 622 21 .778 30 . 850 1 . 00 41 . 66 O
ATOM 943 0E2 GLU A 130 13 .273 22 .229 32 . 910 1 . 00 31 . 05 O
ATOM 944 N SER A 131 10 . 981 23 .188 35 . 042 1 . 00 21 . 56 N
ATOM 945 CA SER A 131 e11 .218 23 . 091 36 .482 1 . 00 22 . 08 C
ATOM 946 C SER A 131 12 .354 22 .145 36 . 859 1 . 00 21 .38 C
ATOM 947 O SER A 131 12 .480 21 .762 38 . 025 1 . 00 22 . 99 O
ATOM 948 CB SER A 131 11 . 507 24 .465 37 . 054 1 . 00 21 . 55 C
ATOM 949 OG SER A 131 12 . 717 24 . 945 36 . 546 1 . 00 24 . 75 O
ATOM 950 N ASN A 132 e13 . 164 21 .776 35 . 874 1 . 00 24 . 32 N
ATOM 951 CA ASN A 132 14 .366 20 . 945 36 . 087 1 . 00 26 . 66 C
ATOM 952 C ASN A 132 15 .282 21 .460 37 .222 1 . 00 24 . 81 C
ATOM 953 O ASN A 132 15 . 909 20 .669 37 . 929 1 . 00 24 .20 O
ATOM 954 CB ASN A 132 13 . 962 19 .454 36 .290 1 . 00 25 . 55 C
ATOM 955 CG ASN A 132 *13 .432 18 .805 35 . 008 1 . 00 25 .26 C
ATOM 956 OD1 ASN A 132 12 .407 18 .132 35 . 018 1 . 00 26 .44 O
ATOM 957 ND2 ASN A 132 14 . 114 19 . 027 33 . 905 1 . O0 27 . 89 N
ATOM 958 N ILE A 133 15 .327 22 .785 37 .410 1 . 00 29 . 00 N
ATOM 959 CA ILE A 133 16 . 084 23 .392 38 . 540 1 . 00 32 .29 C
ATOM 960 C ILE A 133 e17 . 548 22 . 950 38 . 547 1 . 00 28 . 17 C
ATOM 961 O ILE A 133 18 . 063 22 .573 39 . 590 1 . 00 28 . 86 O
ATOM 962 CB ILE A 133 16 . 037 24 . 981 38 . 608 1 . 00 30 . 69 C
ATOM 963 CG1 ILE A 133 16 . 013 25 .599 37 .208 1 . 00 39 . 82 C
ATOM 964 CD1 ILE A 133 16 . 658 27 . 001 37 . 117 1 . 00 38 .31 C
ATOM 965 CG2 ILE A 133 e14 . 880 25 .465 39 .482 1 . 00 37 .25 C
ATOM 966 N ASN A 134 18 . 187 22 . 979 37 .375 1 . 00 30 . 05 N
ATOM 967 CA ASN A 134 19 . 588 22 .542 37 .226 1 . 00 32 . 00 C
ATOM 968 C ASN A 134 19 . 813 21 . 039 37 .390 1 . 00 32 . 67 C
ATOM 969 O ASN A 134 20 . 959 20 .598 37 .447 1 . 00 35 .49 O
ATOM 970 CB ASN A 134 *20 . 176 23 . 017 35 . 893 1 . 00 33 .46 C
ATOM 971 N LYS A 135 18 . 733 20 .255 37 .497 1 . 00 31 . 61 N
ATOM 972 CA LYS A 135 18 . 842 18 .801 37 . 662 1 . 00 28 . 91 C
ATOM 973 C LYS A
135 18 . 525 18 .288 39 . 047 1 . 00 28 . 95 C
ATOM 974 O LYS A
135 18 . 851 17 .133 39 .376 1 . 00 29 . 87 O
ATOM 975 CB LYS A
135 e17 . 993 18 . 085 36 . 618 1 . 00 30 .26 C
ATOM 976 CG LYS A
135 18 . 512 18 .309 35 .219 1 . 00 28 . 90 C
ATOM 977 CD LYS A 135 17 . 610 17 .754 34 . 157 1 . 00 34 . 53 C
ATOM 978 CE LYS A 135 18 .306 17 . 900 32 . 814 1 . 00 43 .26 C
ATOM 979 NZ LYS A 135 17 . 554 17 .224 31 . 736 1 . OO 47 . 95 N
ATOM 980 N LEU A 136 e17 . 953 19 .143 39 . 894 1 . 00 27 . 61 N
ATOM 981 CA LEU A 136 17 . 502 18 .693 41 .206 1 . 00 28 . 18 C
ATOM 982 C LEU A 136 18 . 653 18 .324 42 . 098 1 . 00 30 . 07 C
ATOM 983 O LEU A 136 19 . 692 18 . 960 42 . 044 1 . 00 27 .49 O
ATOM 984 CB LEU A 136 16 . 677 19 .763 41 . 928 1 . 00 30 . 03 C
ATOM 985 CG LEU A 136 e15 . 504 20 .357 41 . 172 1 . 00 33 . 01 C
ATOM 986 CD1 LEU A 136 14 . 967 21 .587 41 . 935 1 . 00 35 .29 C
ATOM 987 CD2 LEU A 136 14 .443 19 .299 40 . 931 1 . 00 23 .30 C
ATOM 988 N THR A 137 18 .434 17 .295 42 . 923 1 . 00 30 . 67 N
ATOM 989 CA THR A 137 19 .342 16 . 931 43 . 997 1 . 00 30 .22 C
Patent Application Publication Mar. 5, 2009 Sheet 19 of 138 US 2009/0062286 A1

Figure 1A-19
Atom Type Residue # X Y Z Occ B Type

ATOM 990 C THR A 137 19 .262 17 . 944 45 . 148 1 . 00 32 .34 C

ATOM 991 O THR A 137 18 .312 18 . 739 45 .251 1 . 00 28 .42 O
ATOM 992 CE THR A 137 19 . 059 15 . 513 44 . 526 1 . 00 31 . 05 C
ATOM 993 OG1 THR A 137 17 .832 15 . 501 45 .258 1 . 00 31 .33 O
ATOM 994 CG2 THR A 137 18 . 962 14 . 525 43 .393 1 . O0 32 . 85 C
ATOM 995 N GLU A 138 20 .270 1'7 . 915 46 . 020 1 . O0 32 . 76 N
ATOM 996 CA GLU A 138 20 .308 18 . 842 47 . 133 1 . O0 31 .39 C
ATOM 997 C GLU A 138 19 .182 18 . 547 48 . 122 1 . O0 30 . 88 C
ATOM 998 O GLU A 138 18 .598 19 .464 48 . 725 1 . 00 31 . 82 O
ATOM 999 CB GLU A 138 21 .678 18 . 815 47 . 810 1 . 00 33 . 85 C
ATOM 1000 N ASP A 139 18 .871 17 .267 48 .288 1 . 00 31 .44 N
ATOM 1001 CA ASP A 139 17 .823 16 . 869 49 .206 1 . 00 28 . O7 C
ATOM 1002 C ASP A 139 16 .463 17 .382 48 . 716 1 . 00 27 .29 C
ATOM 1003 O ASP A 139 15 .631 17 . 825 49 . 510 1 . 00 25 . 73 O
ATOM 1004 CB ASP A 139 17 .793 15 .349 49 .343 1 . 00 31 . 98 C
ATOM 1005 N LYS A 140 16 .238 17 .282 47 .413 1 . 00 25 . 99 N
ATOM 1006 CA LYS A 140 15 . 035 17 . 822 46 . 812 1 . 00 26 . 71 C
ATOM 1007 C LYS A 140 14 . 937 19 .368 46 . 946 1 . 00 26 . 91 C
ATOM 1008 O LYS A 140 13 .891 19 . 893 47 .299 1 . 00 29 . 52 O
ATOM 1009 CB LYS A 140 14 . 928 17 .392 45 .348 1 . 00 27 . 87 C
ATOM 1010 CG LYS A 140 13 .605 17 . 821 44 . 673 1 . 00 31 . 00 C
ATOM 1011 CD LYS A 140 12 .361 17 .383 45 .481 1 . 00 49 . 68 C
ATOM 1012 CE LYS A 140 11 .765 16 . 063 44 . 972 1 . 00 54 .38 C
ATOM 1013 NZ LYS A 140 e12 .624 14 . 885 45 .279 1 . 00 61 . 92 N
ATOM 1014 N LYS A 141 16 . 024 20 . 077 46 . 665 1 . 00 27 . 96 N
ATOM 1015 CA LYS A 141 16 . 045 21 . 547 46 . 790 1 . 00 28 . 17 C
ATOM 1016 C LYS A 141 15 .770 21 . 949 48 .228 1 . 00 27 . 83 C
ATOM 1017 O LYS A 141 15 . 084 22 . 927 48 .479 1 . 00 29 .24 O
ATOM 1018 CB LYS A 141 17 .361 22 . 129 46 .294 1 . O0 27 . 81 C
ATOM 1019 CG LYS A 141 P17 .505 22 . 079 44 . 815 1 . 00 28 . 83 C
ATOM 1020 CD LYS A 141 18 .733 22 . 799 44 .358 1 . 00 39 .22 C
ATOM 1021 CE LYS A 141 e19 . 936 21 . 888 44 .336 1 . 00 43 . 90 C
ATOM 1022 NZ LYS A 141 21 . 080 22 . 584 43 . 675 1 . 00 50 . 14 N
ATOM 1023 N GLU A 142 e16 .244 21 . 145 49 . 176 1 . 00 29 . 62 N
ATOM 1024 CA GLU A 142 15 . 917 21 .382 50 . 570 1 . 00 30 .44 C
ATOM 1025 C GLU A 142 e14 .415 21 .236 50 . 849 1 . 00 29 .48 C
ATOM 1026 O GLU A 142 13 .840 22 . 071 51 . 537 1 . 00 30 . 57 O
ATOM 1027 CB GLU A 142 e16 .763 20 .498 51 . 502 1 . 00 30 . 72 C
ATOM 1028 CG GLU A 142 16 .491 20 . 709 52 . 984 1 . 00 34 . 13 C
ATOM 1029 N GLY A 143 P13 .792 20 . 177 50 . 331 1 . O0 31 . 98 N
ATOM 1030 CA GLY A 143 12 .342 19 . 978 50 .480 1 . 00 30 . 89 C
ATOM 1031 C GLY A 143 P11 .525 21 . 103 49 . 848 1 . O0 29 . 75 C
ATOM 1032 O GLY A 143 10 .487 21 . 502 50 .378 1 . 00 30 . 85 O
ATOM 1033 N LEU A 144 e12 . 007 21 . 618 48 . 724 1 . 00 28 .40 N
ATOM 1034 CA LEU A 144 11 .369 22 . 755 48 . 054 1 . O0 27 . 77 C
ATOM 1035 C LEU A 144 e11 .409 24 . 007 48 . 913 1 . O0 27 . 97 C
ATOM 1036 O LEU A 144 10 .428 24 . 712 49 . 031 1 . O0 26 .44 O
ATOM 1037 CB LEU A 144 e12 . 014 23 . 027 46 . 698 1 . O0 28 . 77 C
ATOM 1038 CG LEU A 144 11 .772 22 . 049 45 . 561 1 . O0 26 . 09 C
ATOM 1039 CD1 LEU A 144 P12 .538 22 .481 44 . 356 1 . O0 31 . 86 C
ATOM 1040 CD2 LEU A 144 10 .288 21 . 855 45 .231 1 . O0 41 . 16 C
ATOM 1041 N ARG A 145 e12 .564 24 .268 49 . 525 1 . 00 3O . 16 N
ATOM 1042 CA ARG A 145 12 .731 25 .398 50 .426 1 . O0 29 . 67 C
ATOM 1043 C ARG A 145 11 .840 25 .255 51 . 664 1 . O0 27 . 56 C
ATOM 1044 O ARG A 145 11 .345 26 .229 52 . 169 1 . O0 26 .35 O