ADA2A
706
Total Contact Pairs
79
Significant Changes
7.32
Max Increase
-9.49
Max Decrease
Interactive snake plot
GPCRdb-style topology. Click the view buttons to recolor residues by different data layers. Toggle contact links to draw significant residue-residue contacts as arcs. Click loop labels (ICL/ECL) to expand or collapse loop regions.
Color convention: blue = active-favoring, red = inactive-favoring.
Top 100 conformational changes
Residue pairs with the largest RRCS changes between active and inactive states. GPCRdb numbering in parentheses. Highlighted rows exceed the significance threshold.
| Rank | Residue 1 | Residue 2 | Active RRCS | Inactive RRCS | ΔRRCS | Magnitude |
|---|---|---|---|---|---|---|
| 1 | GLU282 | PRO283 | 0.000 | 9.491 | -9.491 | HIGH |
| 2 | PHE104 (2.60x59) | TRP120 (3.24x24) | 0.000 | 8.475 | -8.475 | HIGH |
| 3 | GLU327 | ARG328 | 7.324 | 0.000 | +7.324 | HIGH |
| 4 | GLU204 (45.51x51) | ARG420 (7.32x31) | 7.171 | 0.732 | +6.439 | HIGH |
| 5 | ASP145 (3.49x49) | ARG160 (34.57x57) | 7.802 | 1.520 | +6.282 | HIGH |
| 6 | LYS454 (8.56x56) | ARG458 (8.60x60) | 0.263 | 6.157 | -5.894 | HIGH |
| 7 | THR442 (7.54x54) | PHE448 (8.50x50) | 5.762 | 0.000 | +5.762 | HIGH |
| 8 | ARG301 | ASP302 | 0.000 | 5.662 | -5.662 | HIGH |
| 9 | THR242 (5.69x69) | GLU384 (6.30x30) | 5.641 | 0.000 | +5.641 | HIGH |
| 10 | GLN4 | GLU5 | 0.000 | 5.616 | -5.616 | HIGH |
| 11 | ARG3 | GLU5 | 5.534 | 0.000 | +5.534 | HIGH |
| 12 | TYR231 (5.58x58) | ALA392 (6.38x38) | 0.000 | 5.393 | -5.393 | HIGH |
| 13 | ASP145 (3.49x49) | ARG146 (3.50x50) | 0.008 | 5.171 | -5.163 | HIGH |
| 14 | ILE443 (7.55x55) | ARG449 (8.51x51) | 5.140 | 0.000 | +5.140 | HIGH |
| 15 | ASP315 | ARG450 (8.52x52) | 0.000 | 4.888 | -4.888 | MED |
| 16 | GLU5 | GLN6 | 4.839 | 0.000 | +4.839 | MED |
| 17 | CYS401 (6.47x47) | PHE429 (7.41x40) | 4.125 | 8.954 | -4.829 | MED |
| 18 | THR242 (5.69x69) | ARG380 (6.26x26) | 4.801 | 0.000 | +4.801 | MED |
| 19 | GLU122 (3.26x26) | ILE187 | 6.371 | 1.734 | +4.636 | MED |
| 20 | SER186 | GLN208 (5.35x36) | 4.628 | 0.000 | +4.628 | MED |
| 21 | PHE398 (6.44x44) | ASN433 (7.45x45) | 0.786 | 5.209 | -4.423 | MED |
| 22 | LYS118 (3.22x22) | GLU122 (3.26x26) | 4.435 | 0.109 | +4.326 | MED |
| 23 | ARG146 (3.50x50) | TYR441 (7.53x53) | 4.294 | 0.000 | +4.294 | MED |
| 24 | TRP402 (6.48x48) | ASN433 (7.45x45) | 5.658 | 1.454 | +4.205 | MED |
| 25 | GLN287 | LEU288 | 0.000 | 4.184 | -4.184 | MED |
| 26 | PHE398 (6.44x44) | TRP402 (6.48x48) | 2.294 | 6.360 | -4.066 | MED |
| 27 | SER339 | GLN340 | 0.000 | 4.025 | -4.025 | MED |
| 28 | ASN157 (34.54x54) | ARG160 (34.57x57) | 0.349 | 4.234 | -3.886 | MED |
| 29 | ASN433 (7.45x45) | ASN437 (7.49x49) | 4.310 | 0.439 | +3.872 | MED |
| 30 | ASN206 | GLN208 (5.35x36) | 8.373 | 4.574 | +3.799 | MED |
| 31 | GLU109 (2.65x64) | TRP428 (7.40x39) | 3.758 | 0.026 | +3.732 | MED |
| 32 | PRO326 | GLU327 | 3.606 | 0.000 | +3.606 | MED |
| 33 | MET227 (5.54x54) | PHE398 (6.44x44) | 3.601 | 0.081 | +3.520 | MED |
| 34 | VAL390 (6.36x36) | PHE444 (7.56x56) | 6.129 | 2.639 | +3.491 | MED |
| 35 | TYR235 (5.62x62) | LYS239 (5.66x66) | 5.052 | 1.609 | +3.443 | MED |
| 36 | LEU284 | PRO285 | 0.215 | 3.649 | -3.434 | MED |
| 37 | ASN206 | TYR211 (5.38x39) | 3.033 | 6.442 | -3.409 | MED |
| 38 | ILE136 (3.40x40) | TRP402 (6.48x48) | 3.387 | 0.000 | +3.387 | MED |
| 39 | GLY65 (1.49x49) | PRO438 (7.50x50) | 1.238 | 4.614 | -3.376 | MED |
| 40 | LEU288 | ASN289 | 0.000 | 3.344 | -3.344 | MED |
| 41 | PHE220 (5.47x47) | PHE406 (6.52x52) | 10.515 | 13.815 | -3.301 | MED |
| 42 | LEU422 (7.34x33) | PHE426 (7.38x37) | 0.050 | 3.332 | -3.282 | MED |
| 43 | LEU139 (3.43x43) | TYR441 (7.53x53) | 3.230 | 0.000 | +3.230 | MED |
| 44 | PHE387 (6.33x33) | LEU391 (6.37x37) | 0.298 | 3.482 | -3.184 | MED |
| 45 | PHE181 (4.58x58) | ILE185 (4.62x62) | 3.103 | 0.000 | +3.103 | MED |
| 46 | TYR156 (34.53x53) | ARG164 (4.41x41) | 3.084 | 0.000 | +3.084 | MED |
| 47 | PHE405 (6.51x51) | PHE427 (7.39x38) | 4.221 | 7.227 | -3.006 | MED |
| 48 | GLU155 | LYS159 | 3.083 | 0.134 | +2.949 | MED |
| 49 | ASP94 | SER135 | 3.251 | 0.328 | +2.923 | MED |
| 50 | TYR231 (5.58x58) | ILE395 | 0.554 | 3.388 | -2.834 | MED |
| 51 | TYR43 | GLU109 (2.65x64) | 2.617 | 5.437 | -2.820 | MED |
| 52 | VAL129 | SER180 | 1.682 | 4.487 | -2.805 | MED |
| 53 | PHE74 | LYS80 | 0.815 | 3.612 | -2.797 | MED |
| 54 | TYR235 (5.62x62) | THR388 | 2.752 | 0.000 | +2.752 | MED |
| 55 | TYR43 | LYS424 | 3.177 | 0.445 | +2.732 | MED |
| 56 | ILE150 | ARG241 | 1.730 | 4.433 | -2.702 | MED |
| 57 | ASP315 | HIS316 | 2.680 | 0.000 | +2.680 | MED |
| 58 | LEU139 (3.43x43) | ASN437 (7.49x49) | 2.672 | 0.000 | +2.672 | MED |
| 59 | GLN83 | ARG146 (3.50x50) | 0.000 | 2.667 | -2.667 | MED |
| 60 | PHE116 | TRP120 (3.24x24) | 0.702 | 3.309 | -2.607 | MED |
| 61 | TYR113 | GLU200 | 2.864 | 0.279 | +2.586 | MED |
| 62 | TRP114 | CYS203 | 4.864 | 7.445 | -2.580 | MED |
| 63 | ARG146 (3.50x50) | PHE387 (6.33x33) | 0.000 | 2.560 | -2.560 | MED |
| 64 | TRP402 (6.48x48) | GLY430 | 5.190 | 7.735 | -2.546 | MED |
| 65 | LEU106 | TRP428 (7.40x39) | 0.262 | 2.764 | -2.502 | MED |
| 66 | TYR441 (7.53x53) | PHE448 (8.50x50) | 0.000 | 2.500 | -2.500 | MED |
| 67 | GLU294 | PRO295 | 2.478 | 0.000 | +2.478 | MED |
| 68 | PRO183 | TYR211 (5.38x39) | 4.839 | 2.382 | +2.457 | MED |
| 69 | HIS446 | ASP447 | 2.456 | 0.000 | +2.456 | MED |
| 70 | CYS132 | TRP402 (6.48x48) | 1.307 | 3.763 | -2.456 | MED |
| 71 | CYS140 | MET227 (5.54x54) | 1.702 | 4.077 | -2.375 | MED |
| 72 | TYR156 (34.53x53) | ARG160 (34.57x57) | 2.541 | 0.216 | +2.325 | MED |
| 73 | SER134 | HIS138 | 0.344 | 2.591 | -2.246 | MED |
| 74 | THR442 (7.54x54) | ARG449 (8.51x51) | 0.233 | 2.474 | -2.241 | MED |
| 75 | PRO265 | ASN266 | 2.689 | 0.463 | +2.226 | MED |
| 76 | VAL400 | PHE429 (7.41x40) | 0.174 | 2.380 | -2.206 | MED |
| 77 | LEU96 | PHE131 | 4.903 | 7.097 | -2.195 | MED |
| 78 | GLU109 (2.65x64) | LYS424 | 6.064 | 8.256 | -2.192 | MED |
| 79 | PHE64 | LEU68 | 0.364 | 2.547 | -2.184 | MED |
| 80 | PHE104 (2.60x59) | TYR124 | 3.663 | 1.557 | +2.106 | LOW |
| 81 | HIS446 | ARG449 (8.51x51) | 0.448 | 2.535 | -2.087 | LOW |
| 82 | GLY112 | ARG202 | 2.303 | 0.218 | +2.085 | LOW |
| 83 | VAL73 | LYS80 | 0.245 | 2.315 | -2.070 | LOW |
| 84 | ARG146 (3.50x50) | ARG160 (34.57x57) | 0.000 | 2.028 | -2.028 | LOW |
| 85 | ILE136 (3.40x40) | PHE398 (6.44x44) | 1.281 | 3.305 | -2.024 | LOW |
| 86 | ARG146 (3.50x50) | SER149 | 0.000 | 1.972 | -1.972 | LOW |
| 87 | LYS118 (3.22x22) | LYS190 | 0.000 | 1.954 | -1.954 | LOW |
| 88 | TRP377 | GLN381 | 0.000 | 1.885 | -1.885 | LOW |
| 89 | TYR211 (5.38x39) | SER215 | 3.563 | 1.685 | +1.878 | LOW |
| 90 | ASN206 | TYR409 | 1.306 | 3.180 | -1.874 | LOW |
| 91 | VAL341 | LYS342 | 0.000 | 1.868 | -1.868 | LOW |
| 92 | ASN108 | CYS203 | 4.321 | 2.490 | +1.831 | LOW |
| 93 | PRO182 | TYR211 (5.38x39) | 1.827 | 0.000 | +1.827 | LOW |
| 94 | ILE179 | TYR211 (5.38x39) | 1.821 | 0.000 | +1.821 | LOW |
| 95 | TRP114 | PHE116 | 4.262 | 2.447 | +1.815 | LOW |
| 96 | PHE221 | PHE406 (6.52x52) | 0.401 | 2.215 | -1.814 | LOW |
| 97 | VAL212 | TYR409 | 5.999 | 7.795 | -1.796 | LOW |
| 98 | VAL97 | ILE102 | 2.662 | 4.454 | -1.792 | LOW |
| 99 | TYR231 (5.58x58) | THR388 | 0.000 | 1.781 | -1.781 | LOW |
| 100 | LEU139 (3.43x43) | PHE398 (6.44x44) | 1.065 | 2.843 | -1.779 | LOW |
Transmembrane domain analysis
Active-favoring residues form stronger contacts in the active state (positive ΔRRCS). Inactive-favoring residues form stronger contacts in the inactive state (negative ΔRRCS). Only residues with |ΔRRCS| ≥ 2.11 are shown (per-receptor significance threshold = max(mean(|Δ|) + σ, 0.2)).
| Segment | Range | Active-favoring residues | Count | Inactive-favoring residues | Count |
|---|---|---|---|---|---|
| TM1 | 65-65 | - | 0 | 65 (-3.4) | 1 |
| TM2 | 104-109 | 109 (3.7) | 1 | 104 (-8.5) | 1 |
| TM3 | 118-146 | 145 (6.3), 122 (4.6), 118 (4.3), 136 (3.4), 139 (3.2) | 5 | 120 (-8.5), 146 (-5.2) | 2 |
| TM4 | 164-185 | 181 (3.1), 185 (3.1), 164 (3.1) | 3 | - | 0 |
| TM5 | 208-242 | 242 (5.6), 208 (4.6), 227 (3.5), 235 (3.4), 239 (3.4) | 5 | 231 (-5.4), 211 (-3.4), 220 (-3.3) | 3 |
| TM6 | 380-406 | 384 (5.6), 380 (4.8), 402 (4.2), 390 (3.5) | 4 | 392 (-5.4), 401 (-4.8), 398 (-4.4), 406 (-3.3), 387 (-3.2), 391 (-3.2), 405 (-3.0) | 7 |
| TM7 | 420-444 | 420 (6.4), 442 (5.8), 443 (5.1), 441 (4.3), 437 (3.9), 428 (3.7), 444 (3.5) | 7 | 429 (-4.8), 433 (-4.4), 438 (-3.4), 422 (-3.3), 426 (-3.3), 427 (-3.0) | 6 |
| Intracellular / Extracellular loops & H8 | |||||
| ICL1 | - | - | 0 | - | 0 |
| ICL2 | 156-160 | 160 (6.3), 156 (3.1) | 2 | 157 (-3.9) | 1 |
| ICL3 | 282-340 | 327 (7.3), 328 (7.3), 326 (3.6) | 3 | 282 (-9.5), 283 (-9.5), 301 (-5.7), 302 (-5.7), 315 (-4.9), 287 (-4.2), 288 (-4.2), 339 (-4.0), 340 (-4.0), 284 (-3.4), 285 (-3.4), 289 (-3.3) | 12 |
| ECL1 | - | - | 0 | - | 0 |
| ECL2 | 186-206 | 204 (6.4), 187 (4.6), 186 (4.6), 206 (3.8) | 4 | - | 0 |
| ECL3 | - | - | 0 | - | 0 |
| H8 | 448-458 | 448 (5.8), 449 (5.1) | 2 | 454 (-5.9), 458 (-5.9), 450 (-4.9) | 3 |
Interactive visualizations
ΔRRCS distribution
Active vs inactive comparison
Residue-wise changes
TM domain breakdown
Variants of interest
107 variants mapped to contact positions, sorted by |ΔRRCS| impact.
| Position | Protein change | DNA change | Allele freq | Het / Hom | ΔRRCS | AM score | Pathogenicity | Conservation | dbSNP |
|---|---|---|---|---|---|---|---|---|---|
| 283 | p.Pro283Leu | c.848C>T | 3.75e-06 | 4 / 0 | 9.49 | 0.090 | BENIGN | 0.39 | rs968526462 |
| 282 | p.Glu282Gln | c.844G>C | 9.36e-07 | 1 / 0 | 9.49 | 0.074 | BENIGN | 0.36 | |
| 120 | p.Trp120Arg | c.358T>A | 6.84e-07 | 1 / 0 | 8.47 | 0.996 | PATHOGENIC | 0.71 | |
| 328 | p.Arg328Ser | c.982C>A | 9.22e-07 | 1 / 0 | 7.32 | 0.173 | BENIGN | 0.37 | rs1354841234 |
| 327 | p.Glu327Lys | c.979G>A | 9.22e-07 | 1 / 0 | 7.32 | 0.147 | BENIGN | 0.47 | rs1843567654 |
| 327 | p.Glu327Asp | c.981G>T | 1.84e-06 | 2 / 0 | 7.32 | - | nan | - | |
| 328 | p.Arg328Leu | c.983G>T | 6.46e-06 | 7 / 0 | 7.32 | - | nan | - | rs1395809551 |
| 420 | p.Arg420Leu | c.1259G>T | 6.84e-07 | 1 / 0 | 6.44 | 0.135 | BENIGN | 0.39 | |
| 204 | p.Glu204Gln | c.610G>C | 1.59e-05 | 23 / 0 | 6.44 | 0.082 | BENIGN | 0.42 | rs746155867 |
| 204 | p.Glu204Lys | c.610G>A | 8.29e-06 | 12 / 0 | 6.44 | - | nan | - | rs746155867 |
| 160 | p.Arg160Ser | c.478C>A | 6.84e-07 | 1 / 0 | 6.28 | 0.999 | PATHOGENIC | 0.82 | |
| 145 | p.Asp145Asn | c.433G>A | 6.84e-07 | 1 / 0 | 6.28 | 0.999 | PATHOGENIC | 0.99 | |
| 160 | p.Arg160Cys | c.478C>T | 3.42e-06 | 5 / 0 | 6.28 | - | nan | - | rs980881935 |
| 160 | p.Arg160His | c.479G>A | 6.84e-07 | 1 / 0 | 6.28 | - | nan | - | |
| 458 | p.Arg458Pro | c.1373G>C | 1.37e-06 | 2 / 0 | 5.89 | 0.317 | BENIGN | 0.76 | |
| 458 | p.Arg458Gln | c.1373G>A | 4.11e-05 | 60 / 0 | 5.89 | - | nan | - | rs369219397 |
| 458 | p.Arg458Leu | c.1373G>T | 9.58e-06 | 14 / 0 | 5.89 | - | nan | - | rs369219397 |
| 442 | p.Thr442Ser | c.1325C>G | 6.84e-07 | 1 / 0 | 5.76 | 0.838 | PATHOGENIC | 0.93 | |
| 302 | p.Asp302Tyr | c.904G>T | 9.43e-07 | 1 / 0 | 5.66 | 0.223 | BENIGN | 0.51 | |
| 301 | p.Arg301Cys | c.901C>T | 2.83e-06 | 3 / 0 | 5.66 | 0.165 | BENIGN | 0.38 | rs775375141 |
| 301 | p.Arg301Ser | c.901C>A | 1.13e-05 | 12 / 0 | 5.66 | - | nan | - | rs775375141 |
| 301 | p.Arg301Gly | c.901C>G | 3.78e-06 | 4 / 0 | 5.66 | - | nan | - | rs775375141 |
| 301 | p.Arg301His | c.902G>A | 4.34e-05 | 42 / 2 | 5.66 | - | nan | - | rs886590597 |
| 384 | p.Glu384Lys | c.1150G>A | 1.37e-06 | 2 / 0 | 5.64 | 0.998 | PATHOGENIC | 0.99 | rs1800036 |
| 242 | p.Thr242Asn | c.725C>A | 5.88e-06 | 8 / 0 | 5.64 | 0.514 | AMBIGUOUS | 0.48 | rs1455284189 |
| 384 | p.Glu384Asp | c.1152G>C | 1.37e-06 | 2 / 0 | 5.64 | - | nan | - | rs1391463412 |
| 5 | p.Glu5Gly | c.14A>G | 7.07e-06 | 9 / 0 | 5.62 | 0.094 | BENIGN | 0.93 | |
| 4 | p.Gln4Glu | c.10C>G | 7.92e-07 | 1 / 0 | 5.62 | 0.059 | BENIGN | 0.83 | |
| 5 | p.Glu5Asp | c.15G>T | 1.57e-06 | 2 / 0 | 5.62 | - | nan | - | rs781303745 |
| 3 | p.Arg3Cys | c.7C>T | 2.71e-05 | 34 / 0 | 5.53 | 0.212 | BENIGN | 0.83 | rs201376588 |
| 3 | p.Arg3His | c.8G>A | 2.38e-06 | 3 / 0 | 5.53 | - | nan | - | rs1843550638 |
| 3 | p.Arg3Leu | c.8G>T | 7.94e-07 | 1 / 0 | 5.53 | - | nan | - | rs1843550638 |
| 3 | p.Arg3Pro | c.8G>C | 1.59e-06 | 2 / 0 | 5.53 | - | nan | - | rs1843550638 |
| 392 | p.Ala392Val | c.1175C>T | 4.79e-06 | 7 / 0 | 5.39 | 0.913 | PATHOGENIC | 0.84 | rs771143397 |
| 146 | p.Arg146Cys | c.436C>T | 8.89e-06 | 13 / 0 | 5.16 | 0.998 | PATHOGENIC | 0.99 | |
| 449 | p.Arg449Cys | c.1345C>T | 4.79e-06 | 7 / 0 | 5.14 | 0.973 | PATHOGENIC | 0.94 | rs1350155054 |
| 443 | p.Ile443Val | c.1327A>G | 1.37e-06 | 2 / 0 | 5.14 | 0.068 | BENIGN | 0.60 | rs747921161 |
| 443 | p.Ile443Asn | c.1328T>A | 1.37e-06 | 2 / 0 | 5.14 | - | nan | - | rs1843571822 |
| 443 | p.Ile443Thr | c.1328T>C | 6.57e-06 | 1 / 0 | 5.14 | - | nan | - | rs1843571822 |
| 449 | p.Arg449His | c.1346G>A | 2.05e-06 | 3 / 0 | 5.14 | - | nan | - | rs765866331 |
| 450 | p.Arg450Ser | c.1348C>A | 6.84e-07 | 1 / 0 | 4.89 | 0.946 | PATHOGENIC | 0.71 | |
| 315 | p.Asp315Asn | c.943G>A | 1.84e-06 | 2 / 0 | 4.89 | 0.338 | BENIGN | 0.44 | |
| 315 | p.Asp315Tyr | c.943G>T | 1.84e-06 | 2 / 0 | 4.89 | - | nan | - | |
| 315 | p.Asp315Glu | c.945C>G | 9.22e-07 | 1 / 0 | 4.89 | - | nan | - | |
| 450 | p.Arg450Cys | c.1348C>T | 2.74e-06 | 4 / 0 | 4.89 | - | nan | - | rs1351738795 |
| 450 | p.Arg450His | c.1349G>A | 6.84e-07 | 1 / 0 | 4.89 | - | nan | - | |
| 6 | p.Gln6Leu | c.17A>T | 1.57e-06 | 2 / 0 | 4.84 | 0.108 | BENIGN | 0.76 | rs745988173 |
| 401 | p.Cys401Tyr | c.1202G>A | 6.84e-07 | 1 / 0 | 4.83 | 0.999 | PATHOGENIC | 0.99 | rs767408029 |
| 429 | p.Phe429Val | c.1285T>G | 6.57e-06 | 1 / 0 | 4.83 | 0.269 | BENIGN | 0.61 | rs1303740549 |
| 401 | p.Cys401Ser | c.1202G>C | 1.37e-06 | 2 / 0 | 4.83 | - | nan | - | rs767408029 |
| 429 | p.Phe429Tyr | c.1286T>A | 6.84e-07 | 1 / 0 | 4.83 | - | nan | - | |
| 429 | p.Phe429Ser | c.1286T>C | 1.37e-06 | 2 / 0 | 4.83 | - | nan | - | |
| 429 | p.Phe429Leu | c.1287C>A | 1.37e-06 | 2 / 0 | 4.83 | - | nan | - | |
| 380 | p.Arg380Trp | c.1138C>T | 6.89e-07 | 1 / 0 | 4.80 | 0.802 | PATHOGENIC | 0.47 | |
| 380 | p.Arg380Gln | c.1139G>A | 6.57e-06 | 1 / 0 | 4.80 | - | nan | - | rs1843569865 |
| 187 | p.Ile187Val | c.559A>G | 2.74e-06 | 4 / 0 | 4.64 | 0.100 | BENIGN | 0.25 | rs746264766 |
| 187 | p.Ile187Met | c.561C>G | 6.59e-06 | 1 / 0 | 4.64 | - | nan | - | rs770163758 |
| 186 | p.Ser186Phe | c.557C>T | 6.86e-07 | 1 / 0 | 4.63 | 0.515 | AMBIGUOUS | 0.33 | rs1564745549 |
| 208 | p.Gln208Lys | c.622C>A | 6.92e-07 | 1 / 0 | 4.63 | 0.108 | BENIGN | 0.58 | |
| 208 | p.Gln208Arg | c.623A>G | 2.77e-06 | 4 / 0 | 4.63 | - | nan | - | |
| 118 | p.Lys118Glu | c.352A>G | 6.84e-07 | 1 / 0 | 4.33 | 0.134 | BENIGN | 0.49 | rs1386786229 |
| 118 | p.Lys118Asn | c.354G>C | 6.84e-07 | 1 / 0 | 4.33 | - | nan | - | rs1282104494 |
| 441 | p.Tyr441His | c.1321T>C | 6.84e-07 | 1 / 0 | 4.29 | 1.000 | PATHOGENIC | 1.00 | |
| 287 | p.Gln287Glu | c.859C>G | 1.34e-05 | 2 / 0 | 4.18 | 0.076 | BENIGN | 0.40 | rs1214982410 |
| 287 | p.Gln287His | c.861G>C | 7.57e-06 | 8 / 0 | 4.18 | - | nan | - | |
| 340 | p.Gln340Glu | c.1018C>G | 1.54e-05 | 17 / 0 | 4.02 | 0.101 | BENIGN | 0.40 | rs1012164206 |
| 437 | p.Asn437Ser | c.1310A>G | 6.61e-06 | 1 / 0 | 3.87 | 0.985 | PATHOGENIC | 1.00 | rs1843571610 |
| 206 | p.Asn206Asp | c.616A>G | 6.91e-07 | 1 / 0 | 3.80 | 0.644 | PATHOGENIC | 0.66 | rs780345065 |
| 206 | p.Asn206Ser | c.617A>G | 6.91e-07 | 1 / 0 | 3.80 | - | nan | - | |
| 206 | p.Asn206Lys | c.618C>A | 6.92e-07 | 1 / 0 | 3.80 | - | nan | - | |
| 428 | p.Trp428Cys | c.1284G>T | 6.84e-07 | 1 / 0 | 3.73 | 0.995 | PATHOGENIC | 0.98 | rs747042142 |
| 109 | p.Glu109Lys | c.325G>A | 6.84e-07 | 1 / 0 | 3.73 | 0.978 | PATHOGENIC | 0.92 | |
| 109 | p.Glu109Gly | c.326A>G | 6.84e-07 | 1 / 0 | 3.73 | - | nan | - | |
| 326 | p.Pro326Ser | c.976C>T | 1.84e-06 | 2 / 0 | 3.61 | 0.082 | BENIGN | 0.41 | |
| 326 | p.Pro326Thr | c.976C>A | 1.84e-06 | 2 / 0 | 3.61 | - | nan | - | |
| 326 | p.Pro326Arg | c.977C>G | 9.22e-07 | 1 / 0 | 3.61 | - | nan | - | |
| 227 | p.Met227Ile | c.681G>C | 2.10e-06 | 3 / 0 | 3.52 | 0.995 | PATHOGENIC | 0.83 | |
| 444 | p.Phe444Val | c.1330T>G | 1.37e-06 | 2 / 0 | 3.49 | 0.996 | PATHOGENIC | 0.98 | |
| 390 | p.Val390Met | c.1168G>A | 1.37e-06 | 2 / 0 | 3.49 | 0.986 | PATHOGENIC | 0.71 | rs375454021 |
| 239 | p.Lys239Gln | c.715A>C | 6.60e-06 | 1 / 0 | 3.44 | 0.784 | PATHOGENIC | 0.73 | rs751070655 |
| 235 | p.Tyr235Phe | c.704A>T | 7.17e-07 | 1 / 0 | 3.44 | 0.429 | AMBIGUOUS | 0.94 | |
| 239 | p.Lys239Arg | c.716A>G | 7.27e-07 | 1 / 0 | 3.44 | - | nan | - | |
| 239 | p.Lys239Asn | c.717G>T | 7.29e-07 | 1 / 0 | 3.44 | - | nan | - | |
| 285 | p.Pro285Ser | c.853C>T | 9.40e-07 | 1 / 0 | 3.43 | 0.108 | BENIGN | 0.40 | |
| 285 | p.Pro285Ala | c.853C>G | 6.68e-06 | 1 / 0 | 3.43 | - | nan | - | rs1264483604 |
| 285 | p.Pro285Thr | c.853C>A | 2.82e-06 | 3 / 0 | 3.43 | - | nan | - | rs1264483604 |
| 285 | p.Pro285Leu | c.854C>T | 9.42e-07 | 1 / 0 | 3.43 | - | nan | - | |
| 136 | p.Ile136Leu | c.406A>C | 1.37e-06 | 2 / 0 | 3.39 | 0.934 | PATHOGENIC | 0.97 | |
| 136 | p.Ile136Thr | c.407T>C | 2.08e-06 | 3 / 0 | 3.39 | - | nan | - | rs1454775700 |
| 438 | p.Pro438Leu | c.1313C>T | 6.84e-07 | 1 / 0 | 3.38 | 0.998 | PATHOGENIC | 1.00 | rs1355733199 |
| 65 | p.Gly65Cys | c.193G>T | 1.37e-06 | 2 / 0 | 3.38 | 0.984 | PATHOGENIC | 1.00 | |
| 65 | p.Gly65Arg | c.193G>C | 6.85e-07 | 1 / 0 | 3.38 | - | nan | - | rs1327634108 |
| 438 | p.Pro438Arg | c.1313C>G | 6.84e-07 | 1 / 0 | 3.38 | - | nan | - | |
| 289 | p.Asn289Asp | c.865A>G | 9.47e-07 | 1 / 0 | 3.34 | 0.211 | BENIGN | 0.47 | rs1589532037 |
| 289 | p.Asn289Ser | c.866A>G | 9.47e-06 | 10 / 0 | 3.34 | - | nan | - | rs1164458352 |
| 422 | p.Leu422Phe | c.1264C>T | 6.56e-06 | 1 / 0 | 3.28 | 0.508 | AMBIGUOUS | 0.76 | rs2134209176 |
| 422 | p.Leu422Arg | c.1265T>G | 2.74e-06 | 4 / 0 | 3.28 | - | nan | - | rs778172898 |
| 181 | p.Phe181Ile | c.541T>A | 8.92e-06 | 13 / 0 | 3.10 | 0.361 | AMBIGUOUS | 0.53 | rs746650953 |
| 185 | p.Ile185Phe | c.553A>T | 6.86e-07 | 1 / 0 | 3.10 | 0.222 | BENIGN | 0.59 | |
| 181 | p.Phe181Tyr | c.542T>A | 6.86e-07 | 1 / 0 | 3.10 | - | nan | - | rs774567101 |
| 181 | p.Phe181Ser | c.542T>C | 6.86e-07 | 1 / 0 | 3.10 | - | nan | - | rs774567101 |
| 185 | p.Ile185Thr | c.554T>C | 2.74e-06 | 4 / 0 | 3.10 | - | nan | - | rs1273594845 |
| 156 | p.Tyr156Cys | c.467A>G | 6.84e-07 | 1 / 0 | 3.08 | 0.998 | PATHOGENIC | 0.83 | |
| 164 | p.Arg164Gly | c.490C>G | 6.84e-07 | 1 / 0 | 3.08 | 0.921 | PATHOGENIC | 0.96 | |
| 405 | p.Phe405Ser | c.1214T>C | 2.05e-06 | 3 / 0 | 3.01 | 0.996 | PATHOGENIC | 0.99 | |
| 405 | p.Phe405Leu | c.1215C>A | 1.37e-06 | 2 / 0 | 3.01 | - | nan | - | |
| 405 | p.Phe405Leu | c.1215C>G | 2.05e-06 | 3 / 0 | 3.01 | - | nan | - | rs1843570649 |
Complete RRCS results
Top 1000 contact pairs by |ΔRRCS|. Significance threshold: |ΔRRCS| ≥ 2.11, computed as max(mean(|Δ|) + σ, 0.2). Highlighted rows indicate significant changes.
| Res1 | AA1 | Res2 | AA2 | Active RRCS | Inactive RRCS | ΔRRCS | |ΔRRCS| |
|---|---|---|---|---|---|---|---|
| 282 | GLU | 283 | PRO | 0.000 | 9.491 | -9.491 | 9.491 |
| 104 | PHE | 120 | TRP | 0.000 | 8.475 | -8.475 | 8.475 |
| 327 | GLU | 328 | ARG | 7.324 | 0.000 | 7.324 | 7.324 |
| 204 | GLU | 420 | ARG | 7.171 | 0.732 | 6.439 | 6.439 |
| 145 | ASP | 160 | ARG | 7.802 | 1.520 | 6.282 | 6.282 |
| 454 | LYS | 458 | ARG | 0.263 | 6.157 | -5.894 | 5.894 |
| 442 | THR | 448 | PHE | 5.762 | 0.000 | 5.762 | 5.762 |
| 301 | ARG | 302 | ASP | 0.000 | 5.662 | -5.662 | 5.662 |
| 242 | THR | 384 | GLU | 5.641 | 0.000 | 5.641 | 5.641 |
| 4 | GLN | 5 | GLU | 0.000 | 5.616 | -5.616 | 5.616 |
| 3 | ARG | 5 | GLU | 5.534 | 0.000 | 5.534 | 5.534 |
| 231 | TYR | 392 | ALA | 0.000 | 5.393 | -5.393 | 5.393 |
| 145 | ASP | 146 | ARG | 0.008 | 5.171 | -5.163 | 5.163 |
| 443 | ILE | 449 | ARG | 5.140 | 0.000 | 5.140 | 5.140 |
| 315 | ASP | 450 | ARG | 0.000 | 4.888 | -4.888 | 4.888 |
| 5 | GLU | 6 | GLN | 4.839 | 0.000 | 4.839 | 4.839 |
| 401 | CYS | 429 | PHE | 4.125 | 8.954 | -4.829 | 4.829 |
| 242 | THR | 380 | ARG | 4.801 | 0.000 | 4.801 | 4.801 |
| 122 | GLU | 187 | ILE | 6.371 | 1.734 | 4.636 | 4.636 |
| 186 | SER | 208 | GLN | 4.628 | 0.000 | 4.628 | 4.628 |
| 398 | PHE | 433 | ASN | 0.786 | 5.209 | -4.423 | 4.423 |
| 118 | LYS | 122 | GLU | 4.435 | 0.109 | 4.326 | 4.326 |
| 146 | ARG | 441 | TYR | 4.294 | 0.000 | 4.294 | 4.294 |
| 402 | TRP | 433 | ASN | 5.658 | 1.454 | 4.205 | 4.205 |
| 287 | GLN | 288 | LEU | 0.000 | 4.184 | -4.184 | 4.184 |
| 398 | PHE | 402 | TRP | 2.294 | 6.360 | -4.066 | 4.066 |
| 339 | SER | 340 | GLN | 0.000 | 4.025 | -4.025 | 4.025 |
| 157 | ASN | 160 | ARG | 0.349 | 4.234 | -3.886 | 3.886 |
| 433 | ASN | 437 | ASN | 4.310 | 0.439 | 3.872 | 3.872 |
| 206 | ASN | 208 | GLN | 8.373 | 4.574 | 3.799 | 3.799 |
| 109 | GLU | 428 | TRP | 3.758 | 0.026 | 3.732 | 3.732 |
| 326 | PRO | 327 | GLU | 3.606 | 0.000 | 3.606 | 3.606 |
| 227 | MET | 398 | PHE | 3.601 | 0.081 | 3.520 | 3.520 |
| 390 | VAL | 444 | PHE | 6.129 | 2.639 | 3.491 | 3.491 |
| 235 | TYR | 239 | LYS | 5.052 | 1.609 | 3.443 | 3.443 |
| 284 | LEU | 285 | PRO | 0.215 | 3.649 | -3.434 | 3.434 |
| 206 | ASN | 211 | TYR | 3.033 | 6.442 | -3.409 | 3.409 |
| 136 | ILE | 402 | TRP | 3.387 | 0.000 | 3.387 | 3.387 |
| 65 | GLY | 438 | PRO | 1.238 | 4.614 | -3.376 | 3.376 |
| 288 | LEU | 289 | ASN | 0.000 | 3.344 | -3.344 | 3.344 |
| 220 | PHE | 406 | PHE | 10.515 | 13.815 | -3.301 | 3.301 |
| 422 | LEU | 426 | PHE | 0.050 | 3.332 | -3.282 | 3.282 |
| 139 | LEU | 441 | TYR | 3.230 | 0.000 | 3.230 | 3.230 |
| 387 | PHE | 391 | LEU | 0.298 | 3.482 | -3.184 | 3.184 |
| 181 | PHE | 185 | ILE | 3.103 | 0.000 | 3.103 | 3.103 |
| 156 | TYR | 164 | ARG | 3.084 | 0.000 | 3.084 | 3.084 |
| 405 | PHE | 427 | PHE | 4.221 | 7.227 | -3.006 | 3.006 |
| 155 | GLU | 159 | LYS | 3.083 | 0.134 | 2.949 | 2.949 |
| 94 | ASP | 135 | SER | 3.251 | 0.328 | 2.923 | 2.923 |
| 231 | TYR | 395 | ILE | 0.554 | 3.388 | -2.834 | 2.834 |
| 43 | TYR | 109 | GLU | 2.617 | 5.437 | -2.820 | 2.820 |
| 129 | VAL | 180 | SER | 1.682 | 4.487 | -2.805 | 2.805 |
| 74 | PHE | 80 | LYS | 0.815 | 3.612 | -2.797 | 2.797 |
| 235 | TYR | 388 | THR | 2.752 | 0.000 | 2.752 | 2.752 |
| 43 | TYR | 424 | LYS | 3.177 | 0.445 | 2.732 | 2.732 |
| 150 | ILE | 241 | ARG | 1.730 | 4.433 | -2.702 | 2.702 |
| 315 | ASP | 316 | HIS | 2.680 | 0.000 | 2.680 | 2.680 |
| 139 | LEU | 437 | ASN | 2.672 | 0.000 | 2.672 | 2.672 |
| 83 | GLN | 146 | ARG | 0.000 | 2.667 | -2.667 | 2.667 |
| 116 | PHE | 120 | TRP | 0.702 | 3.309 | -2.607 | 2.607 |
| 113 | TYR | 200 | GLU | 2.864 | 0.279 | 2.586 | 2.586 |
| 114 | TRP | 203 | CYS | 4.864 | 7.445 | -2.580 | 2.580 |
| 146 | ARG | 387 | PHE | 0.000 | 2.560 | -2.560 | 2.560 |
| 402 | TRP | 430 | GLY | 5.190 | 7.735 | -2.546 | 2.546 |
| 106 | LEU | 428 | TRP | 0.262 | 2.764 | -2.502 | 2.502 |
| 441 | TYR | 448 | PHE | 0.000 | 2.500 | -2.500 | 2.500 |
| 294 | GLU | 295 | PRO | 2.478 | 0.000 | 2.478 | 2.478 |
| 183 | PRO | 211 | TYR | 4.839 | 2.382 | 2.457 | 2.457 |
| 446 | HIS | 447 | ASP | 2.456 | 0.000 | 2.456 | 2.456 |
| 132 | CYS | 402 | TRP | 1.307 | 3.763 | -2.456 | 2.456 |
| 140 | CYS | 227 | MET | 1.702 | 4.077 | -2.375 | 2.375 |
| 156 | TYR | 160 | ARG | 2.541 | 0.216 | 2.325 | 2.325 |
| 134 | SER | 138 | HIS | 0.344 | 2.591 | -2.246 | 2.246 |
| 442 | THR | 449 | ARG | 0.233 | 2.474 | -2.241 | 2.241 |
| 265 | PRO | 266 | ASN | 2.689 | 0.463 | 2.226 | 2.226 |
| 400 | VAL | 429 | PHE | 0.174 | 2.380 | -2.206 | 2.206 |
| 96 | LEU | 131 | PHE | 4.903 | 7.097 | -2.195 | 2.195 |
| 109 | GLU | 424 | LYS | 6.064 | 8.256 | -2.192 | 2.192 |
| 64 | PHE | 68 | LEU | 0.364 | 2.547 | -2.184 | 2.184 |
| 104 | PHE | 124 | TYR | 3.663 | 1.557 | 2.106 | 2.106 |
| 446 | HIS | 449 | ARG | 0.448 | 2.535 | -2.087 | 2.087 |
| 112 | GLY | 202 | ARG | 2.303 | 0.218 | 2.085 | 2.085 |
| 73 | VAL | 80 | LYS | 0.245 | 2.315 | -2.070 | 2.070 |
| 146 | ARG | 160 | ARG | 0.000 | 2.028 | -2.028 | 2.028 |
| 136 | ILE | 398 | PHE | 1.281 | 3.305 | -2.024 | 2.024 |
| 146 | ARG | 149 | SER | 0.000 | 1.972 | -1.972 | 1.972 |
| 118 | LYS | 190 | LYS | 0.000 | 1.954 | -1.954 | 1.954 |
| 377 | TRP | 381 | GLN | 0.000 | 1.885 | -1.885 | 1.885 |
| 211 | TYR | 215 | SER | 3.563 | 1.685 | 1.878 | 1.878 |
| 206 | ASN | 409 | TYR | 1.306 | 3.180 | -1.874 | 1.874 |
| 341 | VAL | 342 | LYS | 0.000 | 1.868 | -1.868 | 1.868 |
| 108 | ASN | 203 | CYS | 4.321 | 2.490 | 1.831 | 1.831 |
| 182 | PRO | 211 | TYR | 1.827 | 0.000 | 1.827 | 1.827 |
| 179 | ILE | 211 | TYR | 1.821 | 0.000 | 1.821 | 1.821 |
| 114 | TRP | 116 | PHE | 4.262 | 2.447 | 1.815 | 1.815 |
| 221 | PHE | 406 | PHE | 0.401 | 2.215 | -1.814 | 1.814 |
| 212 | VAL | 409 | TYR | 5.999 | 7.795 | -1.796 | 1.796 |
| 97 | VAL | 102 | ILE | 2.662 | 4.454 | -1.792 | 1.792 |
| 231 | TYR | 388 | THR | 0.000 | 1.781 | -1.781 | 1.781 |
| 139 | LEU | 398 | PHE | 1.065 | 2.843 | -1.779 | 1.779 |
| 133 | THR | 219 | SER | 2.068 | 0.294 | 1.774 | 1.774 |
| 12 | SER | 13 | PHE | 1.773 | 0.000 | 1.773 | 1.773 |
| 235 | TYR | 391 | LEU | 1.768 | 0.000 | 1.768 | 1.768 |
| 401 | CYS | 430 | GLY | 0.446 | 2.207 | -1.760 | 1.760 |
| 142 | ILE | 146 | ARG | 1.848 | 0.125 | 1.723 | 1.723 |
| 94 | ASP | 437 | ASN | 4.872 | 3.154 | 1.718 | 1.718 |
| 285 | PRO | 286 | THR | 0.000 | 1.708 | -1.708 | 1.708 |
| 66 | ASN | 438 | PRO | 6.290 | 4.590 | 1.700 | 1.700 |
| 231 | TYR | 394 | VAL | 1.697 | 0.000 | 1.697 | 1.697 |
| 139 | LEU | 227 | MET | 1.354 | 3.031 | -1.677 | 1.677 |
| 134 | SER | 173 | TRP | 3.473 | 5.142 | -1.669 | 1.669 |
| 377 | TRP | 380 | ARG | 1.654 | 0.000 | 1.654 | 1.654 |
| 148 | TRP | 156 | TYR | 10.789 | 9.166 | 1.624 | 1.624 |
| 146 | ARG | 391 | LEU | 0.000 | 1.622 | -1.622 | 1.622 |
| 425 | PHE | 426 | PHE | 0.008 | 1.629 | -1.621 | 1.621 |
| 142 | ILE | 391 | LEU | 0.000 | 1.608 | -1.608 | 1.608 |
| 282 | GLU | 284 | LEU | 1.567 | 0.000 | 1.567 | 1.567 |
| 82 | PRO | 162 | PRO | 1.004 | 2.565 | -1.561 | 1.561 |
| 244 | VAL | 380 | ARG | 1.554 | 0.000 | 1.554 | 1.554 |
| 238 | ALA | 387 | PHE | 1.549 | 0.000 | 1.549 | 1.549 |
| 18 | SER | 19 | LEU | 1.539 | 0.000 | 1.539 | 1.539 |
| 98 | ALA | 103 | PRO | 0.684 | 2.221 | -1.536 | 1.536 |
| 147 | TYR | 234 | ILE | 1.245 | 2.775 | -1.530 | 1.530 |
| 81 | ALA | 83 | GLN | 1.372 | 2.890 | -1.518 | 1.518 |
| 111 | MET | 113 | TYR | 2.638 | 1.123 | 1.515 | 1.515 |
| 177 | ALA | 181 | PHE | 0.000 | 1.508 | -1.508 | 1.508 |
| 90 | LEU | 138 | HIS | 2.189 | 0.689 | 1.499 | 1.499 |
| 20 | GLN | 22 | ASP | 1.477 | 0.000 | 1.477 | 1.477 |
| 122 | GLU | 184 | LEU | 1.273 | 2.746 | -1.473 | 1.473 |
| 140 | CYS | 226 | ILE | 1.454 | 0.000 | 1.454 | 1.454 |
| 66 | ASN | 94 | ASP | 2.710 | 4.141 | -1.430 | 1.430 |
| 427 | PHE | 431 | TYR | 5.490 | 6.907 | -1.418 | 1.418 |
| 161 | THR | 164 | ARG | 0.638 | 2.055 | -1.418 | 1.418 |
| 369 | VAL | 373 | LYS | 2.519 | 1.116 | 1.403 | 1.403 |
| 202 | ARG | 204 | GLU | 0.904 | 2.248 | -1.344 | 1.344 |
| 302 | ASP | 304 | ASP | 0.000 | 1.340 | -1.340 | 1.340 |
| 342 | LYS | 343 | PRO | 0.406 | 1.745 | -1.339 | 1.339 |
| 143 | SER | 231 | TYR | 2.222 | 3.556 | -1.335 | 1.335 |
| 114 | TRP | 124 | TYR | 2.165 | 3.487 | -1.322 | 1.322 |
| 21 | PRO | 22 | ASP | 1.319 | 0.000 | 1.319 | 1.319 |
| 145 | ASP | 156 | TYR | 4.792 | 6.107 | -1.315 | 1.315 |
| 159 | LYS | 164 | ARG | 5.842 | 4.541 | 1.301 | 1.301 |
| 138 | HIS | 173 | TRP | 3.930 | 2.633 | 1.297 | 1.297 |
| 44 | SER | 47 | VAL | 0.165 | 1.461 | -1.295 | 1.295 |
| 409 | TYR | 423 | PHE | 2.216 | 3.510 | -1.294 | 1.294 |
| 264 | ARG | 266 | ASN | 0.000 | 1.293 | -1.293 | 1.293 |
| 264 | ARG | 265 | PRO | 1.287 | 0.000 | 1.287 | 1.287 |
| 184 | LEU | 187 | ILE | 0.000 | 1.259 | -1.259 | 1.259 |
| 66 | ASN | 434 | SER | 0.972 | 2.218 | -1.246 | 1.246 |
| 239 | LYS | 384 | GLU | 1.229 | 0.000 | 1.229 | 1.229 |
| 144 | LEU | 226 | ILE | 1.214 | 0.000 | 1.214 | 1.214 |
| 220 | PHE | 224 | CYS | 1.930 | 3.140 | -1.210 | 1.210 |
| 403 | PHE | 407 | PHE | 2.434 | 1.225 | 1.208 | 1.208 |
| 131 | PHE | 173 | TRP | 0.700 | 1.897 | -1.197 | 1.197 |
| 237 | ILE | 241 | ARG | 2.115 | 0.919 | 1.196 | 1.196 |
| 90 | LEU | 139 | LEU | 1.522 | 0.338 | 1.184 | 1.184 |
| 71 | ILE | 455 | ILE | 0.725 | 1.900 | -1.176 | 1.176 |
| 42 | PRO | 111 | MET | 0.636 | 1.810 | -1.174 | 1.174 |
| 79 | LEU | 448 | PHE | 4.867 | 3.693 | 1.173 | 1.173 |
| 84 | ASN | 448 | PHE | 1.170 | 0.000 | 1.170 | 1.170 |
| 69 | VAL | 441 | TYR | 0.000 | 1.170 | -1.170 | 1.170 |
| 147 | TYR | 230 | VAL | 2.081 | 0.919 | 1.162 | 1.162 |
| 69 | VAL | 452 | PHE | 1.504 | 2.665 | -1.161 | 1.161 |
| 43 | TYR | 51 | LEU | 0.000 | 1.156 | -1.156 | 1.156 |
| 387 | PHE | 445 | ASN | 0.000 | 1.155 | -1.155 | 1.155 |
| 142 | ILE | 441 | TYR | 1.154 | 0.000 | 1.154 | 1.154 |
| 216 | CYS | 221 | PHE | 3.764 | 4.915 | -1.150 | 1.150 |
| 133 | THR | 176 | SER | 5.044 | 3.893 | 1.150 | 1.150 |
| 86 | PHE | 145 | ASP | 2.013 | 0.865 | 1.149 | 1.149 |
| 62 | THR | 434 | SER | 1.896 | 3.029 | -1.133 | 1.133 |
| 233 | ARG | 236 | GLN | 3.104 | 1.976 | 1.128 | 1.128 |
| 128 | ASP | 132 | CYS | 1.125 | 0.000 | 1.125 | 1.125 |
| 135 | SER | 437 | ASN | 1.122 | 0.000 | 1.122 | 1.122 |
| 90 | LEU | 94 | ASP | 1.510 | 0.410 | 1.100 | 1.100 |
| 120 | TRP | 123 | ILE | 0.000 | 1.100 | -1.100 | 1.100 |
| 83 | GLN | 84 | ASN | 2.638 | 1.545 | 1.093 | 1.093 |
| 440 | ILE | 441 | TYR | 1.073 | 0.000 | 1.073 | 1.073 |
| 136 | ILE | 406 | PHE | 1.063 | 0.000 | 1.063 | 1.063 |
| 313 | SER | 314 | SER | 1.061 | 0.000 | 1.061 | 1.061 |
| 75 | THR | 80 | LYS | 0.000 | 1.061 | -1.061 | 1.061 |
| 405 | PHE | 426 | PHE | 4.207 | 3.165 | 1.043 | 1.043 |
| 251 | PRO | 252 | ASP | 1.038 | 0.000 | 1.038 | 1.038 |
| 209 | LYS | 414 | VAL | 1.036 | 0.000 | 1.036 | 1.036 |
| 42 | PRO | 110 | VAL | 1.262 | 2.296 | -1.034 | 1.034 |
| 231 | TYR | 441 | TYR | 1.031 | 0.000 | 1.031 | 1.031 |
| 445 | ASN | 448 | PHE | 3.106 | 4.137 | -1.031 | 1.031 |
| 270 | PRO | 271 | GLU | 0.000 | 1.030 | -1.030 | 1.030 |
| 380 | ARG | 384 | GLU | 0.000 | 1.027 | -1.027 | 1.027 |
| 83 | GLN | 160 | ARG | 7.156 | 8.178 | -1.022 | 1.022 |
| 149 | SER | 160 | ARG | 1.611 | 0.602 | 1.009 | 1.009 |
| 66 | ASN | 91 | ALA | 7.243 | 6.234 | 1.009 | 1.009 |
| 402 | TRP | 406 | PHE | 2.013 | 3.016 | -1.003 | 1.003 |
| 317 | ALA | 318 | GLU | 0.999 | 0.000 | 0.999 | 0.999 |
| 143 | SER | 230 | VAL | 3.113 | 2.118 | 0.996 | 0.996 |
| 217 | ILE | 222 | ALA | 2.485 | 3.475 | -0.990 | 0.990 |
| 143 | SER | 395 | ILE | 0.000 | 0.987 | -0.987 | 0.987 |
| 323 | PRO | 324 | ARG | 0.982 | 0.000 | 0.982 | 0.982 |
| 181 | PHE | 184 | LEU | 0.517 | 1.496 | -0.979 | 0.979 |
| 402 | TRP | 405 | PHE | 0.000 | 0.972 | -0.972 | 0.972 |
| 228 | ILE | 395 | ILE | 0.960 | 0.000 | 0.960 | 0.960 |
| 74 | PHE | 88 | VAL | 0.661 | 1.612 | -0.951 | 0.951 |
| 234 | ILE | 387 | PHE | 0.944 | 0.000 | 0.944 | 0.944 |
| 394 | VAL | 437 | ASN | 0.000 | 0.940 | -0.940 | 0.940 |
| 45 | LEU | 49 | LEU | 0.000 | 0.939 | -0.939 | 0.939 |
| 150 | ILE | 388 | THR | 0.000 | 0.936 | -0.936 | 0.936 |
| 152 | GLN | 155 | GLU | 0.994 | 0.060 | 0.933 | 0.933 |
| 104 | PHE | 114 | TRP | 2.178 | 1.250 | 0.928 | 0.928 |
| 128 | ASP | 427 | PHE | 1.153 | 2.074 | -0.921 | 0.921 |
| 224 | CYS | 398 | PHE | 1.409 | 0.502 | 0.907 | 0.907 |
| 122 | GLU | 183 | PRO | 0.000 | 0.884 | -0.884 | 0.884 |
| 111 | MET | 115 | TYR | 0.000 | 0.854 | -0.854 | 0.854 |
| 39 | ARG | 113 | TYR | 0.031 | 0.879 | -0.848 | 0.848 |
| 137 | VAL | 172 | VAL | 2.546 | 3.394 | -0.848 | 0.848 |
| 41 | THR | 110 | VAL | 1.384 | 0.542 | 0.842 | 0.842 |
| 442 | THR | 452 | PHE | 3.253 | 2.414 | 0.839 | 0.839 |
| 220 | PHE | 399 | VAL | 0.000 | 0.829 | -0.829 | 0.829 |
| 239 | LYS | 243 | ARG | 1.056 | 1.884 | -0.828 | 0.828 |
| 114 | TRP | 201 | PRO | 4.898 | 5.723 | -0.826 | 0.826 |
| 261 | THR | 262 | GLU | 0.999 | 0.173 | 0.825 | 0.825 |
| 43 | TYR | 47 | VAL | 1.742 | 2.563 | -0.821 | 0.821 |
| 435 | SER | 436 | LEU | 1.175 | 0.364 | 0.811 | 0.811 |
| 114 | TRP | 120 | TRP | 3.110 | 3.920 | -0.810 | 0.810 |
| 123 | ILE | 184 | LEU | 0.241 | 1.049 | -0.808 | 0.808 |
| 347 | LEU | 348 | PRO | 0.926 | 0.122 | 0.804 | 0.804 |
| 51 | LEU | 109 | GLU | 0.823 | 0.025 | 0.798 | 0.798 |
| 73 | VAL | 79 | LEU | 3.027 | 3.824 | -0.798 | 0.798 |
| 93 | ALA | 134 | SER | 1.122 | 0.326 | 0.795 | 0.795 |
| 139 | LEU | 395 | ILE | 0.000 | 0.788 | -0.788 | 0.788 |
| 84 | ASN | 387 | PHE | 0.000 | 0.786 | -0.786 | 0.786 |
| 446 | HIS | 450 | ARG | 3.368 | 2.585 | 0.783 | 0.783 |
| 144 | LEU | 148 | TRP | 1.760 | 2.543 | -0.783 | 0.783 |
| 336 | ALA | 337 | ARG | 0.000 | 0.780 | -0.780 | 0.780 |
| 73 | VAL | 84 | ASN | 0.897 | 1.671 | -0.774 | 0.774 |
| 69 | VAL | 442 | THR | 0.770 | 0.000 | 0.770 | 0.770 |
| 418 | VAL | 423 | PHE | 0.017 | 0.786 | -0.769 | 0.769 |
| 408 | THR | 423 | PHE | 0.635 | 1.403 | -0.768 | 0.768 |
| 296 | ALA | 297 | PRO | 0.199 | 0.958 | -0.759 | 0.759 |
| 354 | ALA | 355 | THR | 0.757 | 0.000 | 0.757 | 0.757 |
| 231 | TYR | 391 | LEU | 3.880 | 4.627 | -0.747 | 0.747 |
| 133 | THR | 180 | SER | 0.000 | 0.745 | -0.745 | 0.745 |
| 129 | VAL | 211 | TYR | 0.740 | 0.000 | 0.740 | 0.740 |
| 202 | ARG | 420 | ARG | 0.000 | 0.739 | -0.739 | 0.739 |
| 94 | ASP | 434 | SER | 10.127 | 10.860 | -0.733 | 0.733 |
| 82 | PRO | 83 | GLN | 0.000 | 0.728 | -0.728 | 0.728 |
| 215 | SER | 219 | SER | 0.850 | 0.122 | 0.727 | 0.727 |
| 381 | GLN | 385 | LYS | 0.000 | 0.724 | -0.724 | 0.724 |
| 408 | THR | 418 | VAL | 2.351 | 1.632 | 0.719 | 0.719 |
| 234 | ILE | 388 | THR | 0.000 | 0.708 | -0.708 | 0.708 |
| 205 | ILE | 423 | PHE | 0.706 | 0.000 | 0.706 | 0.706 |
| 136 | ILE | 219 | SER | 2.690 | 3.394 | -0.704 | 0.704 |
| 219 | SER | 406 | PHE | 1.028 | 1.725 | -0.698 | 0.698 |
| 224 | CYS | 227 | MET | 0.000 | 0.691 | -0.691 | 0.691 |
| 79 | LEU | 84 | ASN | 5.151 | 5.842 | -0.691 | 0.691 |
| 8 | LEU | 9 | ALA | 0.000 | 0.686 | -0.686 | 0.686 |
| 247 | SER | 248 | ARG | 0.000 | 0.685 | -0.685 | 0.685 |
| 136 | ILE | 220 | PHE | 0.000 | 0.684 | -0.684 | 0.684 |
| 147 | TYR | 233 | ARG | 0.934 | 0.252 | 0.682 | 0.682 |
| 308 | LEU | 309 | GLU | 0.682 | 0.000 | 0.682 | 0.682 |
| 390 | VAL | 441 | TYR | 0.000 | 0.680 | -0.680 | 0.680 |
| 286 | THR | 287 | GLN | 0.000 | 0.667 | -0.667 | 0.667 |
| 443 | ILE | 444 | PHE | 3.535 | 4.193 | -0.658 | 0.658 |
| 179 | ILE | 219 | SER | 0.658 | 0.000 | 0.658 | 0.658 |
| 86 | PHE | 169 | ILE | 2.917 | 2.259 | 0.658 | 0.658 |
| 382 | ASN | 385 | LYS | 0.000 | 0.647 | -0.647 | 0.647 |
| 90 | LEU | 142 | ILE | 0.647 | 0.000 | 0.647 | 0.647 |
| 87 | LEU | 387 | PHE | 0.000 | 0.647 | -0.647 | 0.647 |
| 132 | CYS | 431 | TYR | 0.645 | 0.000 | 0.645 | 0.645 |
| 393 | VAL | 440 | ILE | 0.000 | 0.641 | -0.641 | 0.641 |
| 419 | PRO | 421 | THR | 0.641 | 0.000 | 0.641 | 0.641 |
| 105 | SER | 428 | TRP | 0.000 | 0.635 | -0.635 | 0.635 |
| 390 | VAL | 440 | ILE | 0.000 | 0.632 | -0.632 | 0.632 |
| 312 | SER | 313 | SER | 0.626 | 0.000 | 0.626 | 0.626 |
| 82 | PRO | 165 | ILE | 2.164 | 2.789 | -0.625 | 0.625 |
| 246 | PRO | 377 | TRP | 0.623 | 0.000 | 0.623 | 0.623 |
| 224 | CYS | 228 | ILE | 0.623 | 0.000 | 0.623 | 0.623 |
| 179 | ILE | 215 | SER | 0.610 | 0.000 | 0.610 | 0.610 |
| 136 | ILE | 227 | MET | 0.000 | 0.606 | -0.606 | 0.606 |
| 133 | THR | 179 | ILE | 0.352 | 0.955 | -0.602 | 0.602 |
| 291 | ALA | 292 | PRO | 0.602 | 0.000 | 0.602 | 0.602 |
| 272 | ARG | 273 | SER | 0.000 | 0.596 | -0.596 | 0.596 |
| 139 | LEU | 394 | VAL | 0.000 | 0.595 | -0.595 | 0.595 |
| 68 | LEU | 452 | PHE | 3.702 | 4.293 | -0.590 | 0.590 |
| 126 | ALA | 184 | LEU | 1.517 | 2.106 | -0.589 | 0.589 |
| 160 | ARG | 165 | ILE | 0.161 | 0.747 | -0.587 | 0.587 |
| 205 | ILE | 409 | TYR | 2.120 | 2.706 | -0.586 | 0.586 |
| 49 | LEU | 53 | CYS | 0.584 | 0.000 | 0.584 | 0.584 |
| 113 | TYR | 115 | TYR | 0.851 | 1.432 | -0.581 | 0.581 |
| 93 | ALA | 173 | TRP | 2.004 | 1.429 | 0.575 | 0.575 |
| 101 | VAL | 124 | TYR | 2.259 | 2.832 | -0.573 | 0.573 |
| 50 | THR | 54 | LEU | 0.000 | 0.568 | -0.568 | 0.568 |
| 206 | ASN | 207 | ASP | 0.000 | 0.567 | -0.567 | 0.567 |
| 412 | THR | 418 | VAL | 1.442 | 0.876 | 0.566 | 0.566 |
| 295 | PRO | 296 | ALA | 0.000 | 0.565 | -0.565 | 0.565 |
| 107 | ALA | 111 | MET | 0.000 | 0.564 | -0.564 | 0.564 |
| 401 | CYS | 433 | ASN | 2.272 | 1.708 | 0.563 | 0.563 |
| 118 | LYS | 187 | ILE | 0.926 | 0.364 | 0.562 | 0.562 |
| 283 | PRO | 284 | LEU | 0.002 | 0.563 | -0.561 | 0.561 |
| 389 | PHE | 444 | PHE | 0.000 | 0.560 | -0.560 | 0.560 |
| 72 | ALA | 79 | LEU | 2.123 | 2.681 | -0.558 | 0.558 |
| 217 | ILE | 223 | PRO | 0.228 | 0.786 | -0.558 | 0.558 |
| 221 | PHE | 407 | PHE | 0.000 | 0.556 | -0.556 | 0.556 |
| 205 | ILE | 405 | PHE | 0.000 | 0.552 | -0.552 | 0.552 |
| 42 | PRO | 112 | GLY | 1.333 | 1.882 | -0.549 | 0.549 |
| 390 | VAL | 445 | ASN | 0.000 | 0.543 | -0.543 | 0.543 |
| 137 | VAL | 176 | SER | 0.239 | 0.781 | -0.542 | 0.542 |
| 105 | SER | 427 | PHE | 0.608 | 0.067 | 0.541 | 0.541 |
| 90 | LEU | 135 | SER | 2.875 | 2.335 | 0.540 | 0.540 |
| 244 | VAL | 377 | TRP | 0.535 | 0.000 | 0.535 | 0.535 |
| 395 | ILE | 399 | VAL | 0.602 | 0.067 | 0.535 | 0.535 |
| 89 | SER | 138 | HIS | 5.617 | 5.086 | 0.530 | 0.530 |
| 405 | PHE | 423 | PHE | 2.058 | 2.587 | -0.530 | 0.530 |
| 93 | ALA | 131 | PHE | 0.198 | 0.727 | -0.528 | 0.528 |
| 230 | VAL | 231 | TYR | 0.527 | 0.000 | 0.527 | 0.527 |
| 126 | ALA | 180 | SER | 2.527 | 2.003 | 0.524 | 0.524 |
| 143 | SER | 234 | ILE | 0.000 | 0.523 | -0.523 | 0.523 |
| 69 | VAL | 91 | ALA | 0.073 | 0.591 | -0.519 | 0.519 |
| 146 | ARG | 388 | THR | 0.000 | 0.518 | -0.518 | 0.518 |
| 3 | ARG | 4 | GLN | 0.000 | 0.517 | -0.517 | 0.517 |
| 48 | THR | 110 | VAL | 1.181 | 0.667 | 0.514 | 0.514 |
| 440 | ILE | 444 | PHE | 0.000 | 0.510 | -0.510 | 0.510 |
| 140 | CYS | 223 | PRO | 1.528 | 2.035 | -0.507 | 0.507 |
| 58 | LEU | 432 | CYS | 1.513 | 2.020 | -0.507 | 0.507 |
| 359 | THR | 360 | PRO | 0.355 | 0.861 | -0.505 | 0.505 |
| 426 | PHE | 429 | PHE | 0.503 | 0.000 | 0.503 | 0.503 |
| 401 | CYS | 436 | LEU | 0.023 | 0.526 | -0.502 | 0.502 |
| 183 | PRO | 206 | ASN | 0.497 | 0.000 | 0.497 | 0.497 |
| 280 | GLU | 281 | ALA | 0.000 | 0.485 | -0.485 | 0.485 |
| 55 | ALA | 428 | TRP | 0.934 | 1.417 | -0.483 | 0.483 |
| 78 | ALA | 447 | ASP | 0.000 | 0.483 | -0.483 | 0.483 |
| 164 | ARG | 168 | ILE | 0.481 | 0.000 | 0.481 | 0.481 |
| 205 | ILE | 427 | PHE | 0.112 | 0.593 | -0.481 | 0.481 |
| 70 | ILE | 88 | VAL | 0.580 | 1.058 | -0.478 | 0.478 |
| 428 | TRP | 431 | TYR | 0.877 | 0.399 | 0.478 | 0.478 |
| 90 | LEU | 441 | TYR | 0.000 | 0.478 | -0.478 | 0.478 |
| 209 | LYS | 413 | ALA | 5.754 | 5.278 | 0.475 | 0.475 |
| 130 | LEU | 180 | SER | 4.450 | 4.924 | -0.474 | 0.474 |
| 397 | VAL | 436 | LEU | 0.688 | 1.157 | -0.469 | 0.469 |
| 149 | SER | 150 | ILE | 0.000 | 0.469 | -0.469 | 0.469 |
| 62 | THR | 94 | ASP | 1.013 | 1.477 | -0.464 | 0.464 |
| 73 | VAL | 448 | PHE | 1.355 | 0.892 | 0.463 | 0.463 |
| 438 | PRO | 452 | PHE | 0.000 | 0.461 | -0.461 | 0.461 |
| 86 | PHE | 165 | ILE | 3.805 | 3.346 | 0.459 | 0.459 |
| 220 | PHE | 398 | PHE | 0.918 | 1.369 | -0.451 | 0.451 |
| 108 | ASN | 114 | TRP | 3.601 | 4.052 | -0.450 | 0.450 |
| 101 | VAL | 128 | ASP | 3.466 | 3.913 | -0.448 | 0.448 |
| 399 | VAL | 404 | PRO | 0.533 | 0.086 | 0.447 | 0.447 |
| 72 | ALA | 448 | PHE | 0.144 | 0.587 | -0.442 | 0.442 |
| 146 | ARG | 231 | TYR | 0.865 | 0.424 | 0.441 | 0.441 |
| 128 | ASP | 431 | TYR | 5.153 | 5.593 | -0.440 | 0.440 |
| 227 | MET | 231 | TYR | 0.438 | 0.000 | 0.438 | 0.438 |
| 52 | VAL | 106 | LEU | 2.069 | 1.631 | 0.437 | 0.437 |
| 148 | TRP | 152 | GLN | 0.437 | 0.000 | 0.437 | 0.437 |
| 76 | SER | 79 | LEU | 2.701 | 2.265 | 0.436 | 0.436 |
| 70 | ILE | 92 | SER | 0.257 | 0.690 | -0.433 | 0.433 |
| 121 | CYS | 203 | CYS | 6.294 | 6.727 | -0.433 | 0.433 |
| 114 | TRP | 202 | ARG | 0.433 | 0.865 | -0.433 | 0.433 |
| 115 | TYR | 116 | PHE | 0.946 | 0.520 | 0.426 | 0.426 |
| 62 | THR | 435 | SER | 4.772 | 4.350 | 0.422 | 0.422 |
| 73 | VAL | 88 | VAL | 1.416 | 1.830 | -0.414 | 0.414 |
| 72 | ALA | 451 | ALA | 0.412 | 0.821 | -0.409 | 0.409 |
| 68 | LEU | 456 | LEU | 0.864 | 0.460 | 0.404 | 0.404 |
| 43 | TYR | 48 | THR | 2.283 | 2.687 | -0.404 | 0.404 |
| 69 | VAL | 438 | PRO | 1.551 | 1.147 | 0.404 | 0.404 |
| 59 | MET | 98 | ALA | 3.147 | 2.745 | 0.403 | 0.403 |
| 383 | ARG | 447 | ASP | 0.000 | 0.402 | -0.402 | 0.402 |
| 105 | SER | 431 | TYR | 2.161 | 2.562 | -0.401 | 0.401 |
| 146 | ARG | 234 | ILE | 0.268 | 0.667 | -0.399 | 0.399 |
| 133 | THR | 137 | VAL | 0.000 | 0.399 | -0.399 | 0.399 |
| 118 | LYS | 191 | GLY | 0.000 | 0.394 | -0.394 | 0.394 |
| 51 | LEU | 106 | LEU | 0.550 | 0.943 | -0.393 | 0.393 |
| 70 | ILE | 91 | ALA | 1.411 | 1.020 | 0.391 | 0.391 |
| 316 | HIS | 317 | ALA | 0.390 | 0.000 | 0.390 | 0.390 |
| 102 | ILE | 431 | TYR | 1.779 | 2.169 | -0.390 | 0.390 |
| 414 | VAL | 416 | CYS | 0.000 | 0.389 | -0.389 | 0.389 |
| 337 | ARG | 338 | ALA | 1.188 | 0.800 | 0.388 | 0.388 |
| 279 | ALA | 280 | GLU | 2.789 | 2.403 | 0.386 | 0.386 |
| 63 | VAL | 95 | ILE | 0.149 | 0.532 | -0.383 | 0.383 |
| 132 | CYS | 136 | ILE | 0.000 | 0.383 | -0.383 | 0.383 |
| 330 | PRO | 331 | ARG | 0.378 | 0.000 | 0.378 | 0.378 |
| 220 | PHE | 402 | TRP | 2.521 | 2.898 | -0.378 | 0.378 |
| 87 | LEU | 142 | ILE | 0.714 | 0.337 | 0.377 | 0.377 |
| 404 | PRO | 426 | PHE | 7.671 | 8.048 | -0.377 | 0.377 |
| 411 | LEU | 416 | CYS | 6.047 | 6.423 | -0.377 | 0.377 |
| 59 | MET | 103 | PRO | 1.837 | 2.213 | -0.376 | 0.376 |
| 231 | TYR | 234 | ILE | 0.642 | 0.268 | 0.375 | 0.375 |
| 83 | GLN | 145 | ASP | 0.493 | 0.867 | -0.374 | 0.374 |
| 75 | THR | 455 | ILE | 0.737 | 0.363 | 0.374 | 0.374 |
| 58 | LEU | 435 | SER | 1.302 | 1.674 | -0.372 | 0.372 |
| 419 | PRO | 422 | LEU | 1.121 | 0.755 | 0.366 | 0.366 |
| 403 | PHE | 404 | PRO | 1.051 | 1.417 | -0.366 | 0.366 |
| 220 | PHE | 403 | PHE | 4.398 | 4.034 | 0.364 | 0.364 |
| 58 | LEU | 428 | TRP | 0.602 | 0.240 | 0.362 | 0.362 |
| 99 | THR | 100 | LEU | 0.654 | 1.015 | -0.361 | 0.361 |
| 227 | MET | 441 | TYR | 0.359 | 0.000 | 0.359 | 0.359 |
| 397 | VAL | 440 | ILE | 1.845 | 1.488 | 0.357 | 0.357 |
| 340 | GLN | 341 | VAL | 0.000 | 0.354 | -0.354 | 0.354 |
| 97 | VAL | 431 | TYR | 1.502 | 1.148 | 0.354 | 0.354 |
| 97 | VAL | 434 | SER | 0.131 | 0.484 | -0.353 | 0.353 |
| 263 | ARG | 264 | ARG | 0.351 | 0.000 | 0.351 | 0.351 |
| 104 | PHE | 116 | PHE | 4.284 | 3.933 | 0.351 | 0.351 |
| 64 | PHE | 456 | LEU | 0.316 | 0.666 | -0.351 | 0.351 |
| 345 | ASP | 346 | SER | 0.606 | 0.956 | -0.350 | 0.350 |
| 42 | PRO | 109 | GLU | 1.061 | 0.711 | 0.350 | 0.350 |
| 140 | CYS | 144 | LEU | 0.348 | 0.000 | 0.348 | 0.348 |
| 394 | VAL | 440 | ILE | 1.346 | 1.693 | -0.348 | 0.348 |
| 66 | ASN | 95 | ILE | 2.073 | 1.726 | 0.347 | 0.347 |
| 135 | SER | 434 | SER | 0.344 | 0.000 | 0.344 | 0.344 |
| 241 | ARG | 380 | ARG | 0.341 | 0.000 | 0.341 | 0.341 |
| 439 | VAL | 443 | ILE | 0.395 | 0.732 | -0.337 | 0.337 |
| 92 | SER | 173 | TRP | 0.335 | 0.000 | 0.335 | 0.335 |
| 220 | PHE | 221 | PHE | 2.686 | 2.351 | 0.334 | 0.334 |
| 107 | ALA | 116 | PHE | 0.718 | 0.384 | 0.334 | 0.334 |
| 405 | PHE | 406 | PHE | 0.747 | 1.081 | -0.334 | 0.334 |
| 405 | PHE | 409 | TYR | 0.653 | 0.987 | -0.334 | 0.334 |
| 147 | TYR | 148 | TRP | 1.085 | 1.415 | -0.330 | 0.330 |
| 14 | ALA | 15 | PRO | 0.431 | 0.761 | -0.330 | 0.330 |
| 152 | GLN | 156 | TYR | 0.031 | 0.360 | -0.329 | 0.329 |
| 124 | TYR | 203 | CYS | 0.565 | 0.893 | -0.327 | 0.327 |
| 86 | PHE | 141 | ALA | 0.156 | 0.481 | -0.325 | 0.325 |
| 138 | HIS | 172 | VAL | 4.426 | 4.751 | -0.325 | 0.325 |
| 436 | LEU | 440 | ILE | 0.502 | 0.178 | 0.324 | 0.324 |
| 69 | VAL | 448 | PHE | 0.415 | 0.739 | -0.324 | 0.324 |
| 377 | TRP | 378 | ARG | 0.000 | 0.323 | -0.323 | 0.323 |
| 130 | LEU | 173 | TRP | 0.207 | 0.527 | -0.321 | 0.321 |
| 20 | GLN | 21 | PRO | 0.060 | 0.380 | -0.320 | 0.320 |
| 143 | SER | 144 | LEU | 0.320 | 0.000 | 0.320 | 0.320 |
| 111 | MET | 116 | PHE | 0.000 | 0.319 | -0.319 | 0.319 |
| 437 | ASN | 441 | TYR | 0.000 | 0.319 | -0.319 | 0.319 |
| 297 | PRO | 298 | ALA | 0.319 | 0.000 | 0.319 | 0.319 |
| 71 | ILE | 75 | THR | 0.692 | 1.008 | -0.316 | 0.316 |
| 208 | GLN | 211 | TYR | 0.976 | 0.662 | 0.314 | 0.314 |
| 87 | LEU | 391 | LEU | 0.000 | 0.313 | -0.313 | 0.313 |
| 42 | PRO | 43 | TYR | 1.405 | 1.717 | -0.312 | 0.312 |
| 101 | VAL | 127 | LEU | 0.218 | 0.529 | -0.311 | 0.311 |
| 105 | SER | 124 | TYR | 6.152 | 6.461 | -0.309 | 0.309 |
| 209 | LYS | 415 | GLY | 0.308 | 0.000 | 0.308 | 0.308 |
| 219 | SER | 220 | PHE | 0.010 | 0.317 | -0.307 | 0.307 |
| 448 | PHE | 452 | PHE | 1.682 | 1.988 | -0.306 | 0.306 |
| 101 | VAL | 431 | TYR | 2.132 | 2.438 | -0.306 | 0.306 |
| 85 | LEU | 166 | LYS | 0.168 | 0.473 | -0.304 | 0.304 |
| 79 | LEU | 447 | ASP | 0.869 | 1.172 | -0.303 | 0.303 |
| 87 | LEU | 448 | PHE | 0.939 | 1.240 | -0.301 | 0.301 |
| 418 | VAL | 422 | LEU | 0.000 | 0.301 | -0.301 | 0.301 |
| 152 | GLN | 157 | ASN | 0.018 | 0.316 | -0.298 | 0.298 |
| 147 | TYR | 237 | ILE | 0.000 | 0.296 | -0.296 | 0.296 |
| 134 | SER | 176 | SER | 4.101 | 4.393 | -0.292 | 0.292 |
| 82 | PRO | 161 | THR | 0.045 | 0.336 | -0.292 | 0.292 |
| 402 | TRP | 431 | TYR | 0.000 | 0.291 | -0.291 | 0.291 |
| 399 | VAL | 403 | PHE | 0.395 | 0.105 | 0.290 | 0.290 |
| 124 | TYR | 427 | PHE | 0.446 | 0.157 | 0.289 | 0.289 |
| 154 | ILE | 158 | LEU | 0.000 | 0.287 | -0.287 | 0.287 |
| 149 | SER | 156 | TYR | 2.417 | 2.703 | -0.286 | 0.286 |
| 319 | ARG | 320 | PRO | 0.818 | 1.103 | -0.286 | 0.286 |
| 148 | TRP | 153 | ALA | 0.615 | 0.334 | 0.282 | 0.282 |
| 68 | LEU | 455 | ILE | 0.762 | 1.043 | -0.281 | 0.281 |
| 102 | ILE | 428 | TRP | 1.172 | 1.445 | -0.274 | 0.274 |
| 97 | VAL | 132 | CYS | 0.272 | 0.000 | 0.272 | 0.272 |
| 59 | MET | 102 | ILE | 2.216 | 2.485 | -0.270 | 0.270 |
| 440 | ILE | 445 | ASN | 0.000 | 0.269 | -0.269 | 0.269 |
| 93 | ALA | 135 | SER | 0.181 | 0.447 | -0.266 | 0.266 |
| 139 | LEU | 433 | ASN | 0.263 | 0.000 | 0.263 | 0.263 |
| 69 | VAL | 87 | LEU | 0.085 | 0.344 | -0.259 | 0.259 |
| 147 | TYR | 151 | THR | 3.550 | 3.292 | 0.257 | 0.257 |
| 113 | TYR | 201 | PRO | 1.663 | 1.916 | -0.254 | 0.254 |
| 72 | ALA | 452 | PHE | 1.520 | 1.269 | 0.251 | 0.251 |
| 232 | VAL | 236 | GLN | 0.916 | 1.167 | -0.251 | 0.251 |
| 141 | ALA | 168 | ILE | 0.000 | 0.248 | -0.248 | 0.248 |
| 397 | VAL | 433 | ASN | 0.971 | 1.219 | -0.248 | 0.248 |
| 409 | TYR | 412 | THR | 0.404 | 0.650 | -0.246 | 0.246 |
| 149 | SER | 157 | ASN | 0.118 | 0.364 | -0.246 | 0.246 |
| 320 | PRO | 321 | PRO | 0.861 | 0.618 | 0.243 | 0.243 |
| 384 | GLU | 388 | THR | 0.243 | 0.000 | 0.243 | 0.243 |
| 86 | PHE | 168 | ILE | 1.965 | 2.207 | -0.242 | 0.242 |
| 287 | GLN | 289 | ASN | 0.242 | 0.000 | 0.242 | 0.242 |
| 242 | THR | 385 | LYS | 0.000 | 0.242 | -0.242 | 0.242 |
| 404 | PRO | 429 | PHE | 0.000 | 0.241 | -0.241 | 0.241 |
| 221 | PHE | 403 | PHE | 0.072 | 0.312 | -0.239 | 0.239 |
| 76 | SER | 451 | ALA | 0.733 | 0.494 | 0.239 | 0.239 |
| 136 | ILE | 223 | PRO | 1.210 | 1.446 | -0.236 | 0.236 |
| 281 | ALA | 282 | GLU | 0.000 | 0.230 | -0.230 | 0.230 |
| 114 | TRP | 121 | CYS | 7.150 | 7.378 | -0.228 | 0.228 |
| 55 | ALA | 106 | LEU | 1.216 | 1.443 | -0.227 | 0.227 |
| 89 | SER | 92 | SER | 0.226 | 0.000 | 0.226 | 0.226 |
| 129 | VAL | 133 | THR | 0.368 | 0.593 | -0.225 | 0.225 |
| 395 | ILE | 398 | PHE | 0.224 | 0.000 | 0.224 | 0.224 |
| 110 | VAL | 111 | MET | 0.000 | 0.221 | -0.221 | 0.221 |
| 434 | SER | 437 | ASN | 0.217 | 0.000 | 0.217 | 0.217 |
| 58 | LEU | 102 | ILE | 0.197 | 0.413 | -0.217 | 0.217 |
| 57 | LEU | 61 | LEU | 1.523 | 1.306 | 0.216 | 0.216 |
| 96 | LEU | 173 | TRP | 0.231 | 0.447 | -0.216 | 0.216 |
| 407 | PHE | 411 | LEU | 2.822 | 3.037 | -0.215 | 0.215 |
| 245 | PRO | 246 | PRO | 0.871 | 0.656 | 0.215 | 0.215 |
| 218 | GLY | 223 | PRO | 1.915 | 2.129 | -0.214 | 0.214 |
| 55 | ALA | 102 | ILE | 0.214 | 0.000 | 0.214 | 0.214 |
| 172 | VAL | 176 | SER | 0.054 | 0.267 | -0.213 | 0.213 |
| 453 | LYS | 457 | CYS | 0.367 | 0.577 | -0.210 | 0.210 |
| 63 | VAL | 99 | THR | 0.644 | 0.435 | 0.209 | 0.209 |
| 216 | CYS | 406 | PHE | 2.175 | 1.967 | 0.208 | 0.208 |
| 89 | SER | 169 | ILE | 2.021 | 2.228 | -0.207 | 0.207 |
| 130 | LEU | 177 | ALA | 1.821 | 2.025 | -0.204 | 0.204 |
| 181 | PHE | 182 | PRO | 0.718 | 0.515 | 0.203 | 0.203 |
| 165 | ILE | 168 | ILE | 0.000 | 0.203 | -0.203 | 0.203 |
| 150 | ILE | 234 | ILE | 1.067 | 0.865 | 0.202 | 0.202 |
| 168 | ILE | 172 | VAL | 0.091 | 0.293 | -0.202 | 0.202 |
| 401 | CYS | 426 | PHE | 0.120 | 0.321 | -0.201 | 0.201 |
| 394 | VAL | 441 | TYR | 1.496 | 1.296 | 0.200 | 0.200 |
| 100 | LEU | 124 | TYR | 0.000 | 0.199 | -0.199 | 0.199 |
| 216 | CYS | 410 | THR | 1.568 | 1.372 | 0.196 | 0.196 |
| 124 | TYR | 125 | LEU | 1.520 | 1.715 | -0.195 | 0.195 |
| 74 | PHE | 85 | LEU | 0.000 | 0.194 | -0.194 | 0.194 |
| 148 | TRP | 151 | THR | 0.000 | 0.194 | -0.194 | 0.194 |
| 398 | PHE | 399 | VAL | 0.319 | 0.125 | 0.194 | 0.194 |
| 132 | CYS | 406 | PHE | 0.000 | 0.192 | -0.192 | 0.192 |
| 256 | ALA | 257 | PRO | 0.130 | 0.319 | -0.190 | 0.190 |
| 447 | ASP | 450 | ARG | 0.188 | 0.000 | 0.188 | 0.188 |
| 85 | LEU | 169 | ILE | 2.264 | 2.081 | 0.183 | 0.183 |
| 458 | ARG | 461 | ARG | 0.000 | 0.180 | -0.180 | 0.180 |
| 217 | ILE | 221 | PHE | 0.180 | 0.000 | 0.180 | 0.180 |
| 125 | LEU | 205 | ILE | 0.618 | 0.797 | -0.180 | 0.180 |
| 212 | VAL | 410 | THR | 0.000 | 0.179 | -0.179 | 0.179 |
| 408 | THR | 426 | PHE | 2.246 | 2.423 | -0.177 | 0.177 |
| 341 | VAL | 343 | PRO | 0.175 | 0.000 | 0.175 | 0.175 |
| 95 | ILE | 99 | THR | 0.490 | 0.316 | 0.174 | 0.174 |
| 86 | PHE | 142 | ILE | 2.152 | 1.981 | 0.171 | 0.171 |
| 97 | VAL | 103 | PRO | 0.000 | 0.171 | -0.171 | 0.171 |
| 362 | ALA | 366 | GLU | 0.000 | 0.169 | -0.169 | 0.169 |
| 389 | PHE | 393 | VAL | 1.769 | 1.604 | 0.164 | 0.164 |
| 393 | VAL | 444 | PHE | 0.398 | 0.561 | -0.163 | 0.163 |
| 224 | CYS | 399 | VAL | 0.437 | 0.600 | -0.163 | 0.163 |
| 161 | THR | 163 | ARG | 0.497 | 0.335 | 0.162 | 0.162 |
| 257 | PRO | 258 | PRO | 0.717 | 0.559 | 0.158 | 0.158 |
| 262 | GLU | 263 | ARG | 0.000 | 0.157 | -0.157 | 0.157 |
| 85 | LEU | 165 | ILE | 0.853 | 0.701 | 0.152 | 0.152 |
| 386 | ARG | 390 | VAL | 0.151 | 0.000 | 0.151 | 0.151 |
| 84 | ASN | 87 | LEU | 0.316 | 0.463 | -0.147 | 0.147 |
| 6 | GLN | 7 | PRO | 4.321 | 4.176 | 0.146 | 0.146 |
| 221 | PHE | 410 | THR | 0.875 | 1.018 | -0.142 | 0.142 |
| 41 | THR | 42 | PRO | 0.683 | 0.823 | -0.140 | 0.140 |
| 401 | CYS | 402 | TRP | 0.000 | 0.140 | -0.140 | 0.140 |
| 175 | ILE | 179 | ILE | 0.555 | 0.691 | -0.137 | 0.137 |
| 63 | VAL | 67 | VAL | 0.406 | 0.270 | 0.135 | 0.135 |
| 207 | ASP | 208 | GLN | 0.000 | 0.134 | -0.134 | 0.134 |
| 182 | PRO | 183 | PRO | 1.733 | 1.864 | -0.131 | 0.131 |
| 310 | GLU | 311 | SER | 0.131 | 0.000 | 0.131 | 0.131 |
| 311 | SER | 312 | SER | 0.130 | 0.000 | 0.130 | 0.130 |
| 9 | ALA | 10 | GLU | 0.000 | 0.128 | -0.128 | 0.128 |
| 411 | LEU | 414 | VAL | 0.000 | 0.128 | -0.128 | 0.128 |
| 86 | PHE | 138 | HIS | 0.316 | 0.443 | -0.127 | 0.127 |
| 453 | LYS | 458 | ARG | 0.000 | 0.127 | -0.127 | 0.127 |
| 421 | THR | 422 | LEU | 0.126 | 0.000 | 0.126 | 0.126 |
| 444 | PHE | 449 | ARG | 0.126 | 0.000 | 0.126 | 0.126 |
| 83 | GLN | 165 | ILE | 0.000 | 0.126 | -0.126 | 0.126 |
| 284 | LEU | 286 | THR | 0.125 | 0.000 | 0.125 | 0.125 |
| 108 | ASN | 113 | TYR | 1.808 | 1.932 | -0.124 | 0.124 |
| 94 | ASP | 438 | PRO | 0.120 | 0.000 | 0.120 | 0.120 |
| 101 | VAL | 131 | PHE | 0.754 | 0.874 | -0.120 | 0.120 |
| 90 | LEU | 437 | ASN | 0.607 | 0.727 | -0.120 | 0.120 |
| 441 | TYR | 449 | ARG | 0.000 | 0.118 | -0.118 | 0.118 |
| 271 | GLU | 272 | ARG | 1.291 | 1.409 | -0.117 | 0.117 |
| 124 | TYR | 431 | TYR | 0.330 | 0.443 | -0.113 | 0.113 |
| 107 | ALA | 113 | TYR | 0.123 | 0.011 | 0.112 | 0.112 |
| 137 | VAL | 223 | PRO | 0.112 | 0.000 | 0.112 | 0.112 |
| 129 | VAL | 215 | SER | 0.111 | 0.000 | 0.111 | 0.111 |
| 179 | ILE | 218 | GLY | 0.111 | 0.000 | 0.111 | 0.111 |
| 452 | PHE | 456 | LEU | 0.111 | 0.000 | 0.111 | 0.111 |
| 58 | LEU | 62 | THR | 0.634 | 0.744 | -0.110 | 0.110 |
| 82 | PRO | 160 | ARG | 1.348 | 1.240 | 0.108 | 0.108 |
| 96 | LEU | 101 | VAL | 0.855 | 0.748 | 0.107 | 0.107 |
| 455 | ILE | 458 | ARG | 0.106 | 0.000 | 0.106 | 0.106 |
| 43 | TYR | 110 | VAL | 0.000 | 0.105 | -0.105 | 0.105 |
| 197 | GLN | 198 | PRO | 0.626 | 0.521 | 0.105 | 0.105 |
| 335 | LYS | 336 | ALA | 0.380 | 0.484 | -0.104 | 0.104 |
| 52 | VAL | 110 | VAL | 0.442 | 0.338 | 0.104 | 0.104 |
| 225 | LEU | 229 | LEU | 1.164 | 1.060 | 0.104 | 0.104 |
| 85 | LEU | 162 | PRO | 0.052 | 0.156 | -0.103 | 0.103 |
| 134 | SER | 172 | VAL | 0.299 | 0.399 | -0.101 | 0.101 |
| 200 | GLU | 202 | ARG | 0.000 | 0.097 | -0.097 | 0.097 |
| 150 | ILE | 237 | ILE | 0.314 | 0.410 | -0.097 | 0.097 |
| 61 | LEU | 435 | SER | 0.000 | 0.096 | -0.096 | 0.096 |
| 151 | THR | 241 | ARG | 0.000 | 0.096 | -0.096 | 0.096 |
| 174 | VAL | 178 | VAL | 0.038 | 0.133 | -0.095 | 0.095 |
| 136 | ILE | 140 | CYS | 0.000 | 0.094 | -0.094 | 0.094 |
| 212 | VAL | 413 | ALA | 1.224 | 1.317 | -0.093 | 0.093 |
| 169 | ILE | 173 | TRP | 0.932 | 1.025 | -0.093 | 0.093 |
| 452 | PHE | 457 | CYS | 0.092 | 0.000 | 0.092 | 0.092 |
| 445 | ASN | 447 | ASP | 1.282 | 1.192 | 0.090 | 0.090 |
| 96 | LEU | 100 | LEU | 0.614 | 0.704 | -0.090 | 0.090 |
| 407 | PHE | 408 | THR | 0.000 | 0.088 | -0.088 | 0.088 |
| 66 | ASN | 437 | ASN | 0.000 | 0.088 | -0.088 | 0.088 |
| 131 | PHE | 134 | SER | 0.088 | 0.000 | 0.088 | 0.088 |
| 124 | TYR | 128 | ASP | 0.088 | 0.000 | 0.088 | 0.088 |
| 72 | ALA | 455 | ILE | 1.669 | 1.581 | 0.088 | 0.088 |
| 394 | VAL | 444 | PHE | 0.088 | 0.000 | 0.088 | 0.088 |
| 206 | ASN | 212 | VAL | 1.367 | 1.280 | 0.088 | 0.088 |
| 97 | VAL | 101 | VAL | 0.083 | 0.171 | -0.088 | 0.088 |
| 123 | ILE | 127 | LEU | 0.859 | 0.773 | 0.087 | 0.087 |
| 418 | VAL | 419 | PRO | 1.140 | 1.054 | 0.086 | 0.086 |
| 170 | ILE | 174 | VAL | 0.268 | 0.183 | 0.086 | 0.086 |
| 44 | SER | 46 | GLN | 0.316 | 0.401 | -0.085 | 0.085 |
| 411 | LEU | 418 | VAL | 0.158 | 0.073 | 0.085 | 0.085 |
| 127 | LEU | 130 | LEU | 0.311 | 0.226 | 0.084 | 0.084 |
| 59 | MET | 106 | LEU | 0.000 | 0.084 | -0.084 | 0.084 |
| 138 | HIS | 169 | ILE | 0.567 | 0.483 | 0.083 | 0.083 |
| 180 | SER | 211 | TYR | 0.081 | 0.000 | 0.081 | 0.081 |
| 33 | ALA | 34 | PRO | 0.743 | 0.821 | -0.078 | 0.078 |
| 398 | PHE | 403 | PHE | 0.078 | 0.000 | 0.078 | 0.078 |
| 71 | ILE | 76 | SER | 0.000 | 0.078 | -0.078 | 0.078 |
| 101 | VAL | 105 | SER | 0.681 | 0.604 | 0.077 | 0.077 |
| 135 | SER | 139 | LEU | 0.076 | 0.000 | 0.076 | 0.076 |
| 215 | SER | 220 | PHE | 0.018 | 0.094 | -0.076 | 0.076 |
| 62 | THR | 98 | ALA | 1.219 | 1.295 | -0.076 | 0.076 |
| 165 | ILE | 169 | ILE | 0.494 | 0.569 | -0.075 | 0.075 |
| 144 | LEU | 230 | VAL | 0.504 | 0.578 | -0.074 | 0.074 |
| 48 | THR | 52 | VAL | 0.076 | 0.150 | -0.074 | 0.074 |
| 139 | LEU | 142 | ILE | 0.000 | 0.074 | -0.074 | 0.074 |
| 81 | ALA | 84 | ASN | 0.434 | 0.362 | 0.072 | 0.072 |
| 103 | PRO | 104 | PHE | 0.000 | 0.072 | -0.072 | 0.072 |
| 135 | SER | 398 | PHE | 0.000 | 0.071 | -0.071 | 0.071 |
| 216 | CYS | 409 | TYR | 1.474 | 1.542 | -0.068 | 0.068 |
| 55 | ALA | 59 | MET | 0.000 | 0.067 | -0.067 | 0.067 |
| 226 | ILE | 230 | VAL | 0.272 | 0.207 | 0.065 | 0.065 |
| 70 | ILE | 95 | ILE | 0.641 | 0.704 | -0.064 | 0.064 |
| 213 | ILE | 217 | ILE | 0.578 | 0.641 | -0.063 | 0.063 |
| 227 | MET | 395 | ILE | 0.895 | 0.958 | -0.063 | 0.063 |
| 127 | LEU | 131 | PHE | 1.726 | 1.787 | -0.062 | 0.062 |
| 153 | ALA | 157 | ASN | 0.000 | 0.061 | -0.061 | 0.061 |
| 314 | SER | 315 | ASP | 0.056 | 0.000 | 0.056 | 0.056 |
| 78 | ALA | 84 | ASN | 0.000 | 0.055 | -0.055 | 0.055 |
| 63 | VAL | 98 | ALA | 0.459 | 0.514 | -0.055 | 0.055 |
| 307 | ASP | 309 | GLU | 0.000 | 0.054 | -0.054 | 0.054 |
| 143 | SER | 227 | MET | 1.707 | 1.653 | 0.054 | 0.054 |
| 244 | VAL | 245 | PRO | 0.715 | 0.661 | 0.054 | 0.054 |
| 245 | PRO | 247 | SER | 0.053 | 0.000 | 0.053 | 0.053 |
| 61 | LEU | 66 | ASN | 0.000 | 0.053 | -0.053 | 0.053 |
| 1 | MET | 2 | PHE | 0.051 | 0.000 | 0.051 | 0.051 |
| 242 | THR | 243 | ARG | 0.051 | 0.000 | 0.051 | 0.051 |
| 452 | PHE | 455 | ILE | 0.000 | 0.050 | -0.050 | 0.050 |
| 107 | ALA | 112 | GLY | 0.046 | 0.096 | -0.050 | 0.050 |
| 140 | CYS | 143 | SER | 0.049 | 0.000 | 0.049 | 0.049 |
| 239 | LYS | 242 | THR | 0.000 | 0.048 | -0.048 | 0.048 |
| 98 | ALA | 102 | ILE | 0.153 | 0.106 | 0.047 | 0.047 |
| 88 | VAL | 92 | SER | 0.000 | 0.047 | -0.047 | 0.047 |
| 130 | LEU | 131 | PHE | 0.925 | 0.972 | -0.046 | 0.046 |
| 145 | ASP | 165 | ILE | 0.234 | 0.188 | 0.046 | 0.046 |
| 142 | ILE | 231 | TYR | 0.000 | 0.046 | -0.046 | 0.046 |
| 207 | ASP | 212 | VAL | 0.861 | 0.907 | -0.045 | 0.045 |
| 62 | THR | 66 | ASN | 0.773 | 0.818 | -0.045 | 0.045 |
| 222 | ALA | 223 | PRO | 0.884 | 0.839 | 0.045 | 0.045 |
| 151 | THR | 152 | GLN | 0.730 | 0.689 | 0.041 | 0.041 |
| 338 | ALA | 339 | SER | 0.375 | 0.335 | 0.041 | 0.041 |
| 102 | ILE | 103 | PRO | 0.962 | 0.922 | 0.040 | 0.040 |
| 171 | THR | 175 | ILE | 0.824 | 0.863 | -0.038 | 0.038 |
| 100 | LEU | 127 | LEU | 0.000 | 0.037 | -0.037 | 0.037 |
| 106 | LEU | 110 | VAL | 0.779 | 0.743 | 0.036 | 0.036 |
| 47 | VAL | 51 | LEU | 0.741 | 0.705 | 0.035 | 0.035 |
| 161 | THR | 162 | PRO | 0.839 | 0.805 | 0.034 | 0.034 |
| 151 | THR | 237 | ILE | 0.685 | 0.652 | 0.033 | 0.033 |
| 58 | LEU | 431 | TYR | 0.753 | 0.721 | 0.033 | 0.033 |
| 230 | VAL | 234 | ILE | 0.642 | 0.674 | -0.033 | 0.033 |
| 60 | LEU | 65 | GLY | 0.000 | 0.032 | -0.032 | 0.032 |
| 66 | ASN | 69 | VAL | 0.000 | 0.032 | -0.032 | 0.032 |
| 67 | VAL | 95 | ILE | 1.267 | 1.237 | 0.031 | 0.031 |
| 120 | TRP | 124 | TYR | 0.000 | 0.030 | -0.030 | 0.030 |
| 81 | ALA | 82 | PRO | 0.638 | 0.608 | 0.030 | 0.030 |
| 348 | PRO | 349 | ARG | 0.029 | 0.000 | 0.029 | 0.029 |
| 70 | ILE | 74 | PHE | 1.156 | 1.185 | -0.029 | 0.029 |
| 212 | VAL | 216 | CYS | 0.380 | 0.409 | -0.029 | 0.029 |
| 121 | CYS | 125 | LEU | 0.762 | 0.733 | 0.028 | 0.028 |
| 87 | LEU | 90 | LEU | 0.027 | 0.000 | 0.027 | 0.027 |
| 456 | LEU | 457 | CYS | 0.027 | 0.000 | 0.027 | 0.027 |
| 96 | LEU | 99 | THR | 0.000 | 0.027 | -0.027 | 0.027 |
| 121 | CYS | 204 | GLU | 0.000 | 0.026 | -0.026 | 0.026 |
| 397 | VAL | 401 | CYS | 0.469 | 0.443 | 0.026 | 0.026 |
| 62 | THR | 95 | ILE | 0.000 | 0.024 | -0.024 | 0.024 |
| 89 | SER | 173 | TRP | 2.704 | 2.680 | 0.023 | 0.023 |
| 253 | ALA | 254 | VAL | 0.023 | 0.000 | 0.023 | 0.023 |
| 393 | VAL | 397 | VAL | 0.151 | 0.174 | -0.023 | 0.023 |
| 97 | VAL | 131 | PHE | 2.368 | 2.345 | 0.022 | 0.022 |
| 125 | LEU | 203 | CYS | 1.013 | 0.992 | 0.021 | 0.021 |
| 143 | SER | 226 | ILE | 0.020 | 0.000 | 0.020 | 0.020 |
| 412 | THR | 423 | PHE | 0.000 | 0.020 | -0.020 | 0.020 |
| 79 | LEU | 451 | ALA | 0.482 | 0.501 | -0.019 | 0.019 |
| 76 | SER | 78 | ALA | 0.513 | 0.532 | -0.019 | 0.019 |
| 141 | ALA | 172 | VAL | 0.300 | 0.318 | -0.018 | 0.018 |
| 228 | ILE | 232 | VAL | 0.242 | 0.260 | -0.018 | 0.018 |
| 437 | ASN | 438 | PRO | 1.000 | 1.018 | -0.018 | 0.018 |
| 125 | LEU | 204 | GLU | 1.017 | 1.034 | -0.017 | 0.017 |
| 200 | GLU | 201 | PRO | 0.326 | 0.343 | -0.016 | 0.016 |
| 373 | LYS | 377 | TRP | 0.015 | 0.000 | 0.015 | 0.015 |
| 129 | VAL | 179 | ILE | 0.013 | 0.000 | 0.013 | 0.013 |
| 113 | TYR | 202 | ARG | 0.011 | 0.000 | 0.011 | 0.011 |
| 213 | ILE | 414 | VAL | 0.000 | 0.010 | -0.010 | 0.010 |
| 376 | ARG | 383 | ARG | 0.010 | 0.000 | 0.010 | 0.010 |
| 325 | ARG | 326 | PRO | 0.791 | 0.781 | 0.010 | 0.010 |
| 186 | SER | 187 | ILE | 0.008 | 0.000 | 0.008 | 0.008 |
| 51 | LEU | 110 | VAL | 0.000 | 0.007 | -0.007 | 0.007 |
| 69 | VAL | 73 | VAL | 0.006 | 0.000 | 0.006 | 0.006 |
| 213 | ILE | 413 | ALA | 0.399 | 0.393 | 0.006 | 0.006 |
| 432 | CYS | 435 | SER | 0.000 | 0.006 | -0.006 | 0.006 |
| 100 | LEU | 131 | PHE | 1.029 | 1.035 | -0.005 | 0.005 |
| 179 | ILE | 180 | SER | 0.000 | 0.004 | -0.004 | 0.004 |
| 437 | ASN | 440 | ILE | 0.000 | 0.004 | -0.004 | 0.004 |
| 130 | LEU | 176 | SER | 2.907 | 2.910 | -0.002 | 0.002 |
| 67 | VAL | 71 | ILE | 0.899 | 0.898 | 0.001 | 0.001 |
| 87 | LEU | 441 | TYR | 1.303 | 1.304 | -0.001 | 0.001 |
| 390 | VAL | 394 | VAL | 0.001 | 0.000 | 0.001 | 0.001 |
RRCS change distribution
-0.09
Mean ΔRRCS
1.51
Std Dev
-0.08
Median
Magnitude classification
14
High (|Δ| ≥ 5.0)
65
Medium (2.1 ≤ |Δ| < 5.0)
627
Low (|Δ| < 2.1)
Methods
RRCS analysis. Residue-Residue Contact Scores (RRCS) were calculated for each conformational state based on inter-atomic distances. Changes (ΔRRCS) were computed by comparing active and inactive structures predicted by AlphaFold multistate (del Alamo et al., 2022).
Significance threshold. |ΔRRCS| ≥ 2.11, computed as max(mean(|Δ|) + σ, 0.2). The 0.2 floor ensures receptors with very small overall change still surface their largest contacts.
Variant data. Population frequencies from gnomAD v4; pathogenicity predictions from AlphaMissense; conservation from ProtVar / UniProt.
Structural annotation. TM domain boundaries and generic numbering from GPCRdb.
What is RRCS?
Residue-Residue Contact Score (RRCS) measures how strongly two amino acids interact in a protein structure. When a protein changes shape (from inactive to active), these contact strengths change.
ΔRRCS (Delta RRCS) shows the difference in contact strength between states:
- Positive ΔRRCS. Contact is stronger in the active state.
- Negative ΔRRCS. Contact is stronger in the inactive state.
- Large |ΔRRCS|. Significant structural rearrangement.
Residues with large RRCS changes are critical for protein function. Mutations at these positions may disrupt the protein's ability to change shape properly.
Pathogenicity predictions
AlphaMissense predicts whether a mutation harms protein function:
- Pathogenic (score ≥ 0.564): mutation likely damages function.
- Ambiguous (0.34–0.563): effect uncertain.
- Benign (< 0.34): mutation likely tolerated.
Conservation & population data
Conservation score. How well-preserved a position is across species (0 = variable, 1 = conserved). High conservation suggests the position is critical for function.
Allele frequency. How often a variant appears in the population. Rare variants (low frequency) may be more likely to be harmful.
Sources: AlphaFold multistate · RRCS · gnomAD v4 · AlphaMissense · GPCRdb · UniProt / ProtVar