AA2AR
752
Total Contact Pairs
92
Significant Changes
7.22
Max Increase
-6.82
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 | ILE3 (1.29x29) | GLN157 | 7.216 | 0.000 | +7.216 | HIGH |
| 2 | GLN89 (3.37x37) | PHE93 (3.41x41) | 0.624 | 7.446 | -6.822 | HIGH |
| 3 | ASN377 | THR378 | 0.000 | 6.199 | -6.199 | HIGH |
| 4 | THR88 (3.36x36) | TRP246 (6.48x48) | 1.865 | 7.958 | -6.093 | HIGH |
| 5 | ALA289 (7.54x54) | PHE295 (8.50x50) | 5.856 | 0.000 | +5.856 | HIGH |
| 6 | LYS233 (6.35x35) | ARG291 (7.56x56) | 5.733 | 0.000 | +5.733 | HIGH |
| 7 | VAL345 | TRP346 | 0.000 | 5.431 | -5.431 | HIGH |
| 8 | LEU48 (2.46x46) | PRO285 (7.50x50) | 5.430 | 0.000 | +5.430 | HIGH |
| 9 | TYR290 (7.55x55) | ARG296 (8.51x51) | 6.488 | 1.228 | +5.260 | HIGH |
| 10 | GLU169 | HIS264 | 0.000 | 5.215 | -5.215 | HIGH |
| 11 | ALA289 (7.54x54) | ARG296 (8.51x51) | 0.000 | 5.069 | -5.069 | HIGH |
| 12 | TYR43 (2.41x41) | LYS122 (4.43x43) | 5.117 | 0.068 | +5.049 | HIGH |
| 13 | ARG304 (8.59x59) | GLN310 (8.65x65) | 0.000 | 4.907 | -4.907 | MED |
| 14 | PHE180 (5.41x42) | CYS185 (5.46x461) | 0.070 | 4.944 | -4.874 | MED |
| 15 | LEU267 (7.32x31) | TYR271 (7.36x35) | 5.669 | 0.828 | +4.841 | MED |
| 16 | ARG296 (8.51x51) | ARG300 (8.55x55) | 0.368 | 5.116 | -4.748 | MED |
| 17 | TRP29 (1.55x55) | HIS306 (8.61x61) | 0.000 | 4.649 | -4.649 | MED |
| 18 | MET1 (1.27x27) | SER6 (1.32x32) | 0.000 | 4.476 | -4.476 | MED |
| 19 | ILE303 (8.58x58) | LEU308 (8.63x63) | 0.000 | 4.390 | -4.390 | MED |
| 20 | GLY23 (1.49x49) | PRO285 (7.50x50) | 0.000 | 4.370 | -4.370 | MED |
| 21 | ALA204 (5.65x65) | GLU228 (6.30x30) | 4.008 | 0.000 | +4.008 | MED |
| 22 | PHE182 (5.43x44) | HIS250 (6.52x52) | 7.088 | 11.087 | -3.998 | MED |
| 23 | ARG293 (8.48x48) | GLU294 (8.49x49) | 5.148 | 1.150 | +3.997 | MED |
| 24 | MET193 (5.54x54) | PHE242 (6.44x44) | 3.875 | 0.000 | +3.875 | MED |
| 25 | PHE62 (2.60x59) | ILE80 (3.28x28) | 2.845 | 6.710 | -3.865 | MED |
| 26 | ASP52 (2.50x50) | SER91 (3.39x39) | 3.836 | 0.032 | +3.803 | MED |
| 27 | GLU212 (5.73x73) | ARG222 (6.24x24) | 0.000 | 3.733 | -3.733 | MED |
| 28 | PHE242 (6.44x44) | ASN280 (7.45x45) | 2.043 | 5.763 | -3.720 | MED |
| 29 | PHE44 (2.42x42) | ASP101 (3.49x49) | 3.666 | 0.000 | +3.666 | MED |
| 30 | GLN89 (3.37x37) | GLY136 (4.57x57) | 3.657 | 0.000 | +3.657 | MED |
| 31 | ASN181 (5.42x43) | VAL186 (5.47x47) | 0.522 | 4.130 | -3.608 | MED |
| 32 | GLY23 (1.49x49) | PHE286 (7.51x51) | 3.518 | 0.000 | +3.518 | MED |
| 33 | SER90 (3.38x38) | TRP129 (4.50x50) | 4.751 | 8.173 | -3.422 | MED |
| 34 | ILE92 (3.40x40) | TRP246 (6.48x48) | 3.384 | 0.000 | +3.384 | MED |
| 35 | MET1 (1.27x27) | TYR271 (7.36x35) | 0.000 | 3.332 | -3.332 | MED |
| 36 | TYR197 (5.58x58) | ALA236 (6.38x38) | 3.835 | 7.053 | -3.218 | MED |
| 37 | GLN207 (5.68x68) | LEU225 (6.27x27) | 0.362 | 3.576 | -3.214 | MED |
| 38 | SER305 (8.60x60) | ARG309 (8.64x64) | 3.206 | 0.000 | +3.206 | MED |
| 39 | LEU48 (2.46x46) | LEU95 (3.43x43) | 3.918 | 0.772 | +3.147 | MED |
| 40 | ARG293 (8.48x48) | GLN297 (8.52x52) | 2.464 | 5.587 | -3.122 | MED |
| 41 | ALA99 (3.47x47) | TYR197 (5.58x58) | 0.000 | 3.115 | -3.115 | MED |
| 42 | HIS306 (8.61x61) | GLN310 (8.65x65) | 3.043 | 0.000 | +3.043 | MED |
| 43 | TYR103 (3.51x51) | ILE200 (5.61x61) | 0.808 | 3.818 | -3.010 | MED |
| 44 | SER47 (2.45x45) | TRP129 (4.50x50) | 0.000 | 3.004 | -3.004 | MED |
| 45 | SER329 | ASP330 | 2.997 | 0.000 | +2.997 | MED |
| 46 | ALA203 | GLU228 (6.30x30) | 2.895 | 0.000 | +2.895 | MED |
| 47 | ASN280 (7.45x45) | ASN284 | 2.832 | 0.000 | +2.832 | MED |
| 48 | VAL178 | PHE183 | 3.133 | 5.951 | -2.818 | MED |
| 49 | TRP246 (6.48x48) | ASN280 (7.45x45) | 4.416 | 1.625 | +2.790 | MED |
| 50 | TYR197 (5.58x58) | LEU235 | 1.147 | 3.927 | -2.780 | MED |
| 51 | SER305 (8.60x60) | HIS306 (8.61x61) | 0.000 | 2.772 | -2.772 | MED |
| 52 | PHE182 (5.43x44) | PHE183 | 0.499 | 3.230 | -2.731 | MED |
| 53 | LEU96 | MET193 (5.54x54) | 1.299 | 3.987 | -2.688 | MED |
| 54 | TYR9 | TYR271 (7.36x35) | 10.963 | 8.292 | +2.671 | MED |
| 55 | GLY69 | GLN157 | 1.992 | 4.618 | -2.625 | MED |
| 56 | LEU58 | PHE83 | 0.709 | 3.312 | -2.604 | MED |
| 57 | ARG102 | TYR288 | 2.598 | 0.000 | +2.598 | MED |
| 58 | TYR176 | ASN181 (5.42x43) | 5.888 | 3.333 | +2.554 | MED |
| 59 | TYR43 (2.41x41) | SER47 (2.45x45) | 2.546 | 0.000 | +2.546 | MED |
| 60 | LEU115 | ARG120 | 7.056 | 4.539 | +2.517 | MED |
| 61 | VAL45 | TYR288 | 0.961 | 3.460 | -2.499 | MED |
| 62 | ILE106 | GLN207 (5.68x68) | 0.000 | 2.469 | -2.469 | MED |
| 63 | SER234 | ARG291 (7.56x56) | 5.543 | 3.104 | +2.440 | MED |
| 64 | LEU85 | GLN89 (3.37x37) | 2.420 | 0.000 | +2.420 | MED |
| 65 | LEU48 (2.46x46) | ASP52 (2.50x50) | 3.083 | 0.678 | +2.405 | MED |
| 66 | TYR43 (2.41x41) | ALA121 | 2.625 | 0.230 | +2.395 | MED |
| 67 | PRO352 | HIS353 | 0.000 | 2.391 | -2.391 | MED |
| 68 | LEU95 (3.43x43) | MET193 (5.54x54) | 0.706 | 3.037 | -2.331 | MED |
| 69 | ASN24 | PRO285 (7.50x50) | 1.618 | 3.948 | -2.330 | MED |
| 70 | ILE66 | LEU167 | 3.200 | 0.899 | +2.301 | MED |
| 71 | PHE70 | CYS166 | 8.558 | 6.289 | +2.269 | MED |
| 72 | GLN207 (5.68x68) | GLN210 | 2.255 | 0.000 | +2.255 | MED |
| 73 | PHE44 (2.42x42) | ALA97 | 0.913 | 3.155 | -2.242 | MED |
| 74 | TYR179 | ALA184 | 0.000 | 2.236 | -2.236 | MED |
| 75 | GLN89 (3.37x37) | ASN181 (5.42x43) | 2.216 | 0.000 | +2.216 | MED |
| 76 | THR41 | ARG102 | 7.096 | 4.908 | +2.188 | MED |
| 77 | ARG304 (8.59x59) | ARG309 (8.64x64) | 0.000 | 2.187 | -2.187 | MED |
| 78 | LEU95 (3.43x43) | ASN284 | 2.118 | 0.000 | +2.118 | MED |
| 79 | ILE92 (3.40x40) | CYS185 (5.46x461) | 3.243 | 1.130 | +2.114 | MED |
| 80 | THR41 | TYR112 | 2.564 | 0.457 | +2.106 | MED |
| 81 | PHE242 (6.44x44) | TRP246 (6.48x48) | 4.678 | 6.778 | -2.100 | MED |
| 82 | ARG102 | GLU228 (6.30x30) | 0.000 | 2.091 | -2.091 | MED |
| 83 | ARG222 (6.24x24) | GLN226 | 0.000 | 2.069 | -2.069 | MED |
| 84 | ALA51 | TRP129 (4.50x50) | 0.071 | 2.136 | -2.066 | MED |
| 85 | PHE201 | LYS233 (6.35x35) | 0.000 | 2.054 | -2.054 | MED |
| 86 | ARG357 | PRO358 | 2.335 | 0.282 | +2.053 | MED |
| 87 | LEU78 | MET140 | 2.430 | 0.391 | +2.040 | MED |
| 88 | PHE44 (2.42x42) | ALA121 | 3.845 | 1.820 | +2.024 | MED |
| 89 | TYR288 | PHE295 (8.50x50) | 0.000 | 2.024 | -2.024 | MED |
| 90 | GLU13 | VAL275 | 4.904 | 2.884 | +2.019 | MED |
| 91 | TRP143 | ASN175 | 7.255 | 5.252 | +2.004 | MED |
| 92 | THR41 | ASP101 (3.49x49) | 4.127 | 6.108 | -1.982 | MED |
| 93 | CYS82 | GLY136 (4.57x57) | 4.737 | 2.779 | +1.958 | LOW |
| 94 | ALA51 | LEU87 | 0.000 | 1.950 | -1.950 | LOW |
| 95 | TYR9 | SER67 | 3.326 | 1.378 | +1.948 | LOW |
| 96 | ILE66 | PHE168 | 2.742 | 0.795 | +1.947 | LOW |
| 97 | SER47 (2.45x45) | ILE125 | 3.907 | 1.980 | +1.927 | LOW |
| 98 | ARG291 (7.56x56) | ARG296 (8.51x51) | 1.921 | 0.000 | +1.921 | LOW |
| 99 | ALA54 | LEU87 | 1.392 | 3.310 | -1.918 | LOW |
| 100 | LEU249 | ALA273 | 3.472 | 1.568 | +1.903 | 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| ≥ 1.97 are shown (per-receptor significance threshold = max(mean(|Δ|) + σ, 0.2)).
| Segment | Range | Active-favoring residues | Count | Inactive-favoring residues | Count |
|---|---|---|---|---|---|
| TM1 | 1-29 | 3 (7.2) | 1 | 29 (-4.6), 1 (-4.5), 6 (-4.5), 23 (-4.4) | 4 |
| TM2 | 43-62 | 48 (5.4), 43 (5.0), 52 (3.8), 44 (3.7) | 4 | 62 (-3.9), 47 (-3.0) | 2 |
| TM3 | 80-103 | 91 (3.8), 101 (3.7), 92 (3.4), 95 (3.1) | 4 | 89 (-6.8), 93 (-6.8), 88 (-6.1), 80 (-3.9), 90 (-3.4), 99 (-3.1), 103 (-3.0) | 7 |
| TM4 | 122-136 | 122 (5.0), 136 (3.7) | 2 | 129 (-3.4) | 1 |
| TM5 | 180-212 | 204 (4.0), 193 (3.9) | 2 | 180 (-4.9), 185 (-4.9), 182 (-4.0), 212 (-3.7), 181 (-3.6), 186 (-3.6), 197 (-3.2), 207 (-3.2), 200 (-3.0) | 9 |
| TM6 | 222-250 | 233 (5.7), 228 (4.0), 242 (3.9) | 3 | 246 (-6.1), 250 (-4.0), 222 (-3.7), 236 (-3.2), 225 (-3.2) | 5 |
| TM7 | 267-291 | 289 (5.9), 291 (5.7), 285 (5.4), 290 (5.3), 267 (4.8), 271 (4.8), 286 (3.5) | 7 | 280 (-3.7) | 1 |
| Intracellular / Extracellular loops & H8 | |||||
| ICL1 | - | - | 0 | - | 0 |
| ICL2 | - | - | 0 | - | 0 |
| ICL3 | - | - | 0 | - | 0 |
| ECL1 | - | - | 0 | - | 0 |
| ECL2 | 157-169 | 157 (7.2) | 1 | 169 (-5.2) | 1 |
| ECL3 | 264-264 | - | 0 | 264 (-5.2) | 1 |
| H8 | 293-310 | 295 (5.9), 296 (5.3), 293 (4.0), 294 (4.0), 305 (3.2), 309 (3.2) | 6 | 304 (-4.9), 310 (-4.9), 300 (-4.7), 306 (-4.6), 303 (-4.4), 308 (-4.4), 297 (-3.1) | 7 |
Interactive visualizations
ΔRRCS distribution
Active vs inactive comparison
Residue-wise changes
TM domain breakdown
Variants of interest
82 variants mapped to contact positions, sorted by |ΔRRCS| impact.
| Position | Protein change | DNA change | Allele freq | Het / Hom | ΔRRCS | AM score | Pathogenicity | Conservation | dbSNP |
|---|---|---|---|---|---|---|---|---|---|
| 157 | p.Gln157Arg | c.470A>G | 6.84e-07 | 1 / 0 | 7.22 | 0.062 | BENIGN | 0.35 | |
| 3 | p.Ile3Val | c.7A>G | 6.57e-06 | 1 / 0 | 7.22 | 0.060 | BENIGN | 0.41 | rs2043092958 |
| 89 | p.Gln89His | c.267G>C | 6.85e-07 | 1 / 0 | 6.82 | 0.987 | PATHOGENIC | 0.84 | rs780974436 |
| 377 | p.Asn377Thr | c.1130A>C | 7.04e-07 | 1 / 0 | 6.20 | 0.082 | BENIGN | 0.54 | |
| 378 | p.Thr378Met | c.1133C>T | 5.64e-06 | 8 / 0 | 6.20 | 0.069 | BENIGN | 0.31 | rs767866615 |
| 378 | p.Thr378Arg | c.1133C>G | 6.57e-06 | 1 / 0 | 6.20 | - | nan | - | rs767866615 |
| 246 | p.Trp246Arg | c.736T>C | 6.84e-07 | 1 / 0 | 6.09 | 0.999 | PATHOGENIC | 0.99 | |
| 88 | p.Thr88Arg | c.263C>G | 6.85e-07 | 1 / 0 | 6.09 | 0.990 | PATHOGENIC | 0.94 | rs746738083 |
| 88 | p.Thr88Met | c.263C>T | 1.37e-06 | 2 / 0 | 6.09 | - | nan | - | rs746738083 |
| 246 | p.Trp246Leu | c.737G>T | 6.84e-07 | 1 / 0 | 6.09 | - | nan | - | |
| 295 | p.Phe295Leu | c.885C>G | 6.84e-07 | 1 / 0 | 5.86 | 0.999 | PATHOGENIC | 0.90 | rs17650937 |
| 289 | p.Ala289Thr | c.865G>A | 4.10e-06 | 6 / 0 | 5.86 | 0.881 | PATHOGENIC | 0.95 | rs201077707 |
| 289 | p.Ala289Val | c.866C>T | 6.84e-07 | 1 / 0 | 5.86 | - | nan | - | rs1266338168 |
| 233 | p.Lys233Glu | c.697A>G | 6.84e-07 | 1 / 0 | 5.73 | 0.964 | PATHOGENIC | 0.75 | |
| 291 | p.Arg291Cys | c.871C>T | 1.37e-06 | 2 / 0 | 5.73 | 0.685 | PATHOGENIC | 0.78 | rs745714462 |
| 291 | p.Arg291His | c.872G>A | 8.89e-06 | 13 / 0 | 5.73 | - | nan | - | rs769621641 |
| 346 | p.Trp346Arg | c.1036T>C | 6.85e-07 | 1 / 0 | 5.43 | 0.358 | AMBIGUOUS | 0.68 | rs374971289 |
| 345 | p.Val345Met | c.1033G>A | 2.74e-06 | 4 / 0 | 5.43 | 0.100 | BENIGN | 0.65 | rs201030658 |
| 345 | p.Val345Leu | c.1033G>C | 3.42e-06 | 5 / 0 | 5.43 | - | nan | - | rs201030658 |
| 345 | p.Val345Gly | c.1034T>G | 6.85e-07 | 1 / 0 | 5.43 | - | nan | - | rs1568953992 |
| 48 | p.Leu48Pro | c.143T>C | 2.05e-06 | 3 / 0 | 5.43 | 1.000 | PATHOGENIC | 1.00 | rs1270949962 |
| 285 | p.Pro285His | c.854C>A | 6.84e-07 | 1 / 0 | 5.43 | 0.999 | PATHOGENIC | 1.00 | |
| 290 | p.Tyr290Asn | c.868T>A | 6.84e-07 | 1 / 0 | 5.26 | 0.868 | PATHOGENIC | 0.80 | rs1268412903 |
| 296 | p.Arg296Cys | c.886C>T | 2.74e-06 | 4 / 0 | 5.26 | 0.715 | PATHOGENIC | 0.88 | rs201181215 |
| 290 | p.Tyr290Phe | c.869A>T | 2.67e-05 | 39 / 0 | 5.26 | - | nan | - | rs202222894 |
| 296 | p.Arg296His | c.887G>A | 6.84e-06 | 10 / 0 | 5.26 | - | nan | - | rs199792438 |
| 296 | p.Arg296Leu | c.887G>T | 6.84e-07 | 1 / 0 | 5.26 | - | nan | - | rs199792438 |
| 264 | p.His264Tyr | c.790C>T | 6.84e-07 | 1 / 0 | 5.22 | 0.142 | BENIGN | 0.50 | rs1169156621 |
| 264 | p.His264Pro | c.791A>C | 6.84e-07 | 1 / 0 | 5.22 | - | nan | - | |
| 122 | p.Lys122Glu | c.364A>G | 6.57e-06 | 1 / 0 | 5.05 | 0.531 | AMBIGUOUS | 0.46 | rs1380049038 |
| 43 | p.Tyr43Cys | c.128A>G | 4.10e-06 | 6 / 0 | 5.05 | 0.241 | BENIGN | 0.69 | rs2043099509 |
| 43 | p.Tyr43Ser | c.128A>C | 3.42e-06 | 5 / 0 | 5.05 | - | nan | - | |
| 304 | p.Arg304Cys | c.910C>T | 1.37e-05 | 20 / 0 | 4.91 | 0.116 | BENIGN | 0.42 | rs201666195 |
| 310 | p.Gln310Lys | c.928C>A | 6.84e-07 | 1 / 0 | 4.91 | 0.077 | BENIGN | 0.59 | |
| 304 | p.Arg304His | c.911G>A | 1.08e-04 | 158 / 0 | 4.91 | - | nan | - | rs199666600 |
| 310 | p.Gln310Glu | c.928C>G | 6.84e-07 | 1 / 0 | 4.91 | - | nan | - | |
| 310 | p.Gln310Arg | c.929A>G | 6.84e-07 | 1 / 0 | 4.91 | - | nan | - | rs1240519378 |
| 185 | p.Cys185Arg | c.553T>C | 1.37e-06 | 2 / 0 | 4.87 | 0.995 | PATHOGENIC | 0.74 | |
| 185 | p.Cys185Tyr | c.554G>A | 1.37e-06 | 2 / 0 | 4.87 | - | nan | - | |
| 300 | p.Arg300Cys | c.898C>T | 4.10e-06 | 6 / 0 | 4.75 | 0.139 | BENIGN | 0.54 | rs2043329529 |
| 300 | p.Arg300His | c.899G>A | 1.44e-05 | 21 / 0 | 4.75 | - | nan | - | rs4990 |
| 300 | p.Arg300Leu | c.899G>T | 6.84e-07 | 1 / 0 | 4.75 | - | nan | - | rs4990 |
| 29 | p.Trp29Cys | c.87G>C | 3.42e-06 | 5 / 0 | 4.65 | 0.676 | PATHOGENIC | 0.62 | |
| 306 | p.His306Tyr | c.916C>T | 1.37e-06 | 2 / 0 | 4.65 | 0.106 | BENIGN | 0.65 | rs878978641 |
| 306 | p.His306Asp | c.916C>G | 6.84e-07 | 1 / 0 | 4.65 | - | nan | - | rs878978641 |
| 306 | p.His306Arg | c.917A>G | 1.37e-06 | 2 / 0 | 4.65 | - | nan | - | rs778398772 |
| 306 | p.His306Gln | c.918C>A | 6.84e-07 | 1 / 0 | 4.65 | - | nan | - | rs200799056 |
| 306 | p.His306Gln | c.918C>G | 6.84e-07 | 1 / 0 | 4.65 | - | nan | - | |
| 6 | p.Ser6Phe | c.17C>T | 6.85e-07 | 1 / 0 | 4.48 | 0.122 | BENIGN | 0.49 | rs752957802 |
| 308 | p.Leu308Arg | c.923T>G | 6.57e-06 | 1 / 0 | 4.39 | 0.130 | BENIGN | 0.73 | rs781051901 |
| 308 | p.Leu308Pro | c.923T>C | 1.30e-05 | 19 / 0 | 4.39 | - | nan | - | rs781051901 |
| 23 | p.Gly23Asp | c.68G>A | 1.09e-05 | 16 / 0 | 4.37 | 0.998 | PATHOGENIC | 0.97 | rs759676605 |
| 228 | p.Glu228Asp | c.684G>C | 2.05e-06 | 3 / 0 | 4.01 | 0.949 | PATHOGENIC | 0.97 | rs138352666 |
| 204 | p.Ala204Thr | c.610G>A | 6.84e-07 | 1 / 0 | 4.01 | 0.888 | PATHOGENIC | 0.67 | |
| 204 | p.Ala204Val | c.611C>T | 1.37e-06 | 2 / 0 | 4.01 | - | nan | - | rs2043322046 |
| 182 | p.Phe182Leu | c.546C>A | 3.42e-06 | 5 / 0 | 4.00 | 0.996 | PATHOGENIC | 1.00 | rs1267910757 |
| 294 | p.Glu294Lys | c.880G>A | 2.74e-06 | 4 / 0 | 4.00 | 0.949 | PATHOGENIC | 0.57 | rs1390389374 |
| 293 | p.Arg293Cys | c.877C>T | 1.30e-05 | 19 / 0 | 4.00 | 0.399 | AMBIGUOUS | 0.65 | rs142560733 |
| 293 | p.Arg293His | c.878G>A | 2.12e-05 | 31 / 0 | 4.00 | - | nan | - | rs201025926 |
| 294 | p.Glu294Gln | c.880G>C | 6.84e-07 | 1 / 0 | 4.00 | - | nan | - | rs1390389374 |
| 294 | p.Glu294Asp | c.882G>C | 6.16e-06 | 9 / 0 | 4.00 | - | nan | - | rs773303136 |
| 242 | p.Phe242Ser | c.725T>C | 6.84e-07 | 1 / 0 | 3.88 | 0.999 | PATHOGENIC | 0.99 | rs760407585 |
| 193 | p.Met193Thr | c.578T>C | 1.37e-06 | 2 / 0 | 3.88 | 0.989 | PATHOGENIC | 0.98 | |
| 80 | p.Ile80Val | c.238A>G | 6.84e-07 | 1 / 0 | 3.86 | 0.126 | BENIGN | 0.59 | rs2043102637 |
| 52 | p.Asp52Asn | c.154G>A | 6.84e-06 | 10 / 0 | 3.80 | 0.996 | PATHOGENIC | 0.96 | rs199999926 |
| 52 | p.Asp52Gly | c.155A>G | 6.84e-07 | 1 / 0 | 3.80 | - | nan | - | |
| 222 | p.Arg222Trp | c.664C>T | 9.58e-06 | 12 / 1 | 3.73 | 0.241 | BENIGN | 0.60 | rs781339364 |
| 212 | p.Glu212Lys | c.634G>A | 3.42e-06 | 5 / 0 | 3.73 | 0.226 | BENIGN | 0.56 | rs201891365 |
| 222 | p.Arg222Gly | c.664C>G | 6.84e-07 | 1 / 0 | 3.73 | - | nan | - | rs781339364 |
| 222 | p.Arg222Gln | c.665G>A | 1.92e-05 | 28 / 0 | 3.73 | - | nan | - | rs201346032 |
| 280 | p.Asn280Ser | c.839A>G | 1.37e-06 | 2 / 0 | 3.72 | 0.813 | PATHOGENIC | 0.99 | rs779344683 |
| 136 | p.Gly136Ser | c.406G>A | 1.99e-05 | 29 / 0 | 3.66 | 0.931 | PATHOGENIC | 0.94 | rs757137296 |
| 136 | p.Gly136Cys | c.406G>T | 1.37e-06 | 2 / 0 | 3.66 | - | nan | - | |
| 186 | p.Val186Met | c.556G>A | 6.84e-07 | 1 / 0 | 3.61 | 0.890 | PATHOGENIC | 0.83 | rs747066875 |
| 181 | p.Asn181Ser | c.542A>G | 6.84e-07 | 1 / 0 | 3.61 | 0.378 | AMBIGUOUS | 0.89 | |
| 92 | p.Ile92Val | c.274A>G | 6.85e-07 | 1 / 0 | 3.38 | 0.381 | AMBIGUOUS | 0.88 | |
| 225 | p.Leu225Pro | c.674T>C | 6.84e-07 | 1 / 0 | 3.21 | 0.921 | PATHOGENIC | 0.62 | |
| 309 | p.Arg309Lys | c.926G>A | 6.84e-07 | 1 / 0 | 3.21 | 0.115 | BENIGN | 0.49 | rs149670419 |
| 309 | p.Arg309Ser | c.927G>T | 6.84e-07 | 1 / 0 | 3.21 | - | nan | - | |
| 95 | p.Leu95Phe | c.283C>T | 1.37e-06 | 2 / 0 | 3.15 | 0.996 | PATHOGENIC | 0.92 | |
| 99 | p.Ala99Thr | c.295G>A | 1.37e-06 | 2 / 0 | 3.11 | 0.941 | PATHOGENIC | 0.94 | rs1261102428 |
| 103 | p.Tyr103Asp | c.307T>G | 2.75e-06 | 4 / 0 | 3.01 | 0.975 | PATHOGENIC | 0.87 |
Complete RRCS results
Top 1000 contact pairs by |ΔRRCS|. Significance threshold: |ΔRRCS| ≥ 1.97, computed as max(mean(|Δ|) + σ, 0.2). Highlighted rows indicate significant changes.
| Res1 | AA1 | Res2 | AA2 | Active RRCS | Inactive RRCS | ΔRRCS | |ΔRRCS| |
|---|---|---|---|---|---|---|---|
| 3 | ILE | 157 | GLN | 7.216 | 0.000 | 7.216 | 7.216 |
| 89 | GLN | 93 | PHE | 0.624 | 7.446 | -6.822 | 6.822 |
| 377 | ASN | 378 | THR | 0.000 | 6.199 | -6.199 | 6.199 |
| 88 | THR | 246 | TRP | 1.865 | 7.958 | -6.093 | 6.093 |
| 289 | ALA | 295 | PHE | 5.856 | 0.000 | 5.856 | 5.856 |
| 233 | LYS | 291 | ARG | 5.733 | 0.000 | 5.733 | 5.733 |
| 345 | VAL | 346 | TRP | 0.000 | 5.431 | -5.431 | 5.431 |
| 48 | LEU | 285 | PRO | 5.430 | 0.000 | 5.430 | 5.430 |
| 290 | TYR | 296 | ARG | 6.488 | 1.228 | 5.260 | 5.260 |
| 169 | GLU | 264 | HIS | 0.000 | 5.215 | -5.215 | 5.215 |
| 289 | ALA | 296 | ARG | 0.000 | 5.069 | -5.069 | 5.069 |
| 43 | TYR | 122 | LYS | 5.117 | 0.068 | 5.049 | 5.049 |
| 304 | ARG | 310 | GLN | 0.000 | 4.907 | -4.907 | 4.907 |
| 180 | PHE | 185 | CYS | 0.070 | 4.944 | -4.874 | 4.874 |
| 267 | LEU | 271 | TYR | 5.669 | 0.828 | 4.841 | 4.841 |
| 296 | ARG | 300 | ARG | 0.368 | 5.116 | -4.748 | 4.748 |
| 29 | TRP | 306 | HIS | 0.000 | 4.649 | -4.649 | 4.649 |
| 1 | MET | 6 | SER | 0.000 | 4.476 | -4.476 | 4.476 |
| 303 | ILE | 308 | LEU | 0.000 | 4.390 | -4.390 | 4.390 |
| 23 | GLY | 285 | PRO | 0.000 | 4.370 | -4.370 | 4.370 |
| 204 | ALA | 228 | GLU | 4.008 | 0.000 | 4.008 | 4.008 |
| 182 | PHE | 250 | HIS | 7.088 | 11.087 | -3.998 | 3.998 |
| 293 | ARG | 294 | GLU | 5.148 | 1.150 | 3.997 | 3.997 |
| 193 | MET | 242 | PHE | 3.875 | 0.000 | 3.875 | 3.875 |
| 62 | PHE | 80 | ILE | 2.845 | 6.710 | -3.865 | 3.865 |
| 52 | ASP | 91 | SER | 3.836 | 0.032 | 3.803 | 3.803 |
| 212 | GLU | 222 | ARG | 0.000 | 3.733 | -3.733 | 3.733 |
| 242 | PHE | 280 | ASN | 2.043 | 5.763 | -3.720 | 3.720 |
| 44 | PHE | 101 | ASP | 3.666 | 0.000 | 3.666 | 3.666 |
| 89 | GLN | 136 | GLY | 3.657 | 0.000 | 3.657 | 3.657 |
| 181 | ASN | 186 | VAL | 0.522 | 4.130 | -3.608 | 3.608 |
| 23 | GLY | 286 | PHE | 3.518 | 0.000 | 3.518 | 3.518 |
| 90 | SER | 129 | TRP | 4.751 | 8.173 | -3.422 | 3.422 |
| 92 | ILE | 246 | TRP | 3.384 | 0.000 | 3.384 | 3.384 |
| 1 | MET | 271 | TYR | 0.000 | 3.332 | -3.332 | 3.332 |
| 197 | TYR | 236 | ALA | 3.835 | 7.053 | -3.218 | 3.218 |
| 207 | GLN | 225 | LEU | 0.362 | 3.576 | -3.214 | 3.214 |
| 305 | SER | 309 | ARG | 3.206 | 0.000 | 3.206 | 3.206 |
| 48 | LEU | 95 | LEU | 3.918 | 0.772 | 3.147 | 3.147 |
| 293 | ARG | 297 | GLN | 2.464 | 5.587 | -3.122 | 3.122 |
| 99 | ALA | 197 | TYR | 0.000 | 3.115 | -3.115 | 3.115 |
| 306 | HIS | 310 | GLN | 3.043 | 0.000 | 3.043 | 3.043 |
| 103 | TYR | 200 | ILE | 0.808 | 3.818 | -3.010 | 3.010 |
| 47 | SER | 129 | TRP | 0.000 | 3.004 | -3.004 | 3.004 |
| 329 | SER | 330 | ASP | 2.997 | 0.000 | 2.997 | 2.997 |
| 203 | ALA | 228 | GLU | 2.895 | 0.000 | 2.895 | 2.895 |
| 280 | ASN | 284 | ASN | 2.832 | 0.000 | 2.832 | 2.832 |
| 178 | VAL | 183 | PHE | 3.133 | 5.951 | -2.818 | 2.818 |
| 246 | TRP | 280 | ASN | 4.416 | 1.625 | 2.790 | 2.790 |
| 197 | TYR | 235 | LEU | 1.147 | 3.927 | -2.780 | 2.780 |
| 305 | SER | 306 | HIS | 0.000 | 2.772 | -2.772 | 2.772 |
| 182 | PHE | 183 | PHE | 0.499 | 3.230 | -2.731 | 2.731 |
| 96 | LEU | 193 | MET | 1.299 | 3.987 | -2.688 | 2.688 |
| 9 | TYR | 271 | TYR | 10.963 | 8.292 | 2.671 | 2.671 |
| 69 | GLY | 157 | GLN | 1.992 | 4.618 | -2.625 | 2.625 |
| 58 | LEU | 83 | PHE | 0.709 | 3.312 | -2.604 | 2.604 |
| 102 | ARG | 288 | TYR | 2.598 | 0.000 | 2.598 | 2.598 |
| 176 | TYR | 181 | ASN | 5.888 | 3.333 | 2.554 | 2.554 |
| 43 | TYR | 47 | SER | 2.546 | 0.000 | 2.546 | 2.546 |
| 115 | LEU | 120 | ARG | 7.056 | 4.539 | 2.517 | 2.517 |
| 45 | VAL | 288 | TYR | 0.961 | 3.460 | -2.499 | 2.499 |
| 106 | ILE | 207 | GLN | 0.000 | 2.469 | -2.469 | 2.469 |
| 234 | SER | 291 | ARG | 5.543 | 3.104 | 2.440 | 2.440 |
| 85 | LEU | 89 | GLN | 2.420 | 0.000 | 2.420 | 2.420 |
| 48 | LEU | 52 | ASP | 3.083 | 0.678 | 2.405 | 2.405 |
| 43 | TYR | 121 | ALA | 2.625 | 0.230 | 2.395 | 2.395 |
| 352 | PRO | 353 | HIS | 0.000 | 2.391 | -2.391 | 2.391 |
| 95 | LEU | 193 | MET | 0.706 | 3.037 | -2.331 | 2.331 |
| 24 | ASN | 285 | PRO | 1.618 | 3.948 | -2.330 | 2.330 |
| 66 | ILE | 167 | LEU | 3.200 | 0.899 | 2.301 | 2.301 |
| 70 | PHE | 166 | CYS | 8.558 | 6.289 | 2.269 | 2.269 |
| 207 | GLN | 210 | GLN | 2.255 | 0.000 | 2.255 | 2.255 |
| 44 | PHE | 97 | ALA | 0.913 | 3.155 | -2.242 | 2.242 |
| 179 | TYR | 184 | ALA | 0.000 | 2.236 | -2.236 | 2.236 |
| 89 | GLN | 181 | ASN | 2.216 | 0.000 | 2.216 | 2.216 |
| 41 | THR | 102 | ARG | 7.096 | 4.908 | 2.188 | 2.188 |
| 304 | ARG | 309 | ARG | 0.000 | 2.187 | -2.187 | 2.187 |
| 95 | LEU | 284 | ASN | 2.118 | 0.000 | 2.118 | 2.118 |
| 92 | ILE | 185 | CYS | 3.243 | 1.130 | 2.114 | 2.114 |
| 41 | THR | 112 | TYR | 2.564 | 0.457 | 2.106 | 2.106 |
| 242 | PHE | 246 | TRP | 4.678 | 6.778 | -2.100 | 2.100 |
| 102 | ARG | 228 | GLU | 0.000 | 2.091 | -2.091 | 2.091 |
| 222 | ARG | 226 | GLN | 0.000 | 2.069 | -2.069 | 2.069 |
| 51 | ALA | 129 | TRP | 0.071 | 2.136 | -2.066 | 2.066 |
| 201 | PHE | 233 | LYS | 0.000 | 2.054 | -2.054 | 2.054 |
| 357 | ARG | 358 | PRO | 2.335 | 0.282 | 2.053 | 2.053 |
| 78 | LEU | 140 | MET | 2.430 | 0.391 | 2.040 | 2.040 |
| 44 | PHE | 121 | ALA | 3.845 | 1.820 | 2.024 | 2.024 |
| 288 | TYR | 295 | PHE | 0.000 | 2.024 | -2.024 | 2.024 |
| 13 | GLU | 275 | VAL | 4.904 | 2.884 | 2.019 | 2.019 |
| 143 | TRP | 175 | ASN | 7.255 | 5.252 | 2.004 | 2.004 |
| 41 | THR | 101 | ASP | 4.127 | 6.108 | -1.982 | 1.982 |
| 82 | CYS | 136 | GLY | 4.737 | 2.779 | 1.958 | 1.958 |
| 51 | ALA | 87 | LEU | 0.000 | 1.950 | -1.950 | 1.950 |
| 9 | TYR | 67 | SER | 3.326 | 1.378 | 1.948 | 1.948 |
| 66 | ILE | 168 | PHE | 2.742 | 0.795 | 1.947 | 1.947 |
| 47 | SER | 125 | ILE | 3.907 | 1.980 | 1.927 | 1.927 |
| 291 | ARG | 296 | ARG | 1.921 | 0.000 | 1.921 | 1.921 |
| 54 | ALA | 87 | LEU | 1.392 | 3.310 | -1.918 | 1.918 |
| 249 | LEU | 273 | ALA | 3.472 | 1.568 | 1.903 | 1.903 |
| 98 | ILE | 235 | LEU | 0.000 | 1.898 | -1.898 | 1.898 |
| 154 | ASN | 164 | VAL | 6.034 | 4.160 | 1.874 | 1.874 |
| 194 | LEU | 239 | VAL | 1.872 | 0.000 | 1.872 | 1.872 |
| 89 | GLN | 185 | CYS | 2.024 | 3.892 | -1.868 | 1.868 |
| 103 | TYR | 196 | VAL | 3.172 | 1.314 | 1.858 | 1.858 |
| 359 | ASN | 361 | TYR | 0.000 | 1.828 | -1.828 | 1.828 |
| 59 | ALA | 87 | LEU | 2.295 | 0.474 | 1.821 | 1.821 |
| 29 | TRP | 302 | ILE | 2.552 | 4.367 | -1.815 | 1.815 |
| 211 | MET | 225 | LEU | 2.515 | 0.715 | 1.799 | 1.799 |
| 207 | GLN | 228 | GLU | 1.772 | 0.000 | 1.772 | 1.772 |
| 13 | GLU | 60 | ILE | 4.077 | 5.848 | -1.771 | 1.771 |
| 211 | MET | 221 | ALA | 2.682 | 0.927 | 1.755 | 1.755 |
| 341 | HIS | 342 | PRO | 0.061 | 1.814 | -1.753 | 1.753 |
| 222 | ARG | 390 | LEU | 1.752 | 0.000 | 1.752 | 1.752 |
| 34 | ASN | 36 | ASN | 2.699 | 4.439 | -1.741 | 1.741 |
| 3 | ILE | 68 | THR | 1.728 | 0.000 | 1.728 | 1.728 |
| 289 | ALA | 299 | PHE | 0.409 | 2.129 | -1.720 | 1.720 |
| 190 | LEU | 242 | PHE | 2.122 | 0.415 | 1.707 | 1.707 |
| 43 | TYR | 118 | GLY | 0.000 | 1.685 | -1.685 | 1.685 |
| 65 | THR | 70 | PHE | 5.613 | 3.934 | 1.680 | 1.680 |
| 2 | PRO | 157 | GLN | 1.678 | 0.000 | 1.678 | 1.678 |
| 411 | VAL | 412 | SER | 0.000 | 1.677 | -1.677 | 1.677 |
| 6 | SER | 271 | TYR | 1.635 | 0.000 | 1.635 | 1.635 |
| 186 | VAL | 246 | TRP | 1.610 | 0.000 | 1.610 | 1.610 |
| 51 | ALA | 90 | SER | 2.045 | 0.439 | 1.606 | 1.606 |
| 92 | ILE | 186 | VAL | 0.075 | 1.665 | -1.590 | 1.590 |
| 256 | THR | 264 | HIS | 0.904 | 2.493 | -1.588 | 1.588 |
| 154 | ASN | 159 | CYS | 4.409 | 2.851 | 1.558 | 1.558 |
| 297 | GLN | 300 | ARG | 1.554 | 0.000 | 1.554 | 1.554 |
| 208 | LEU | 212 | GLU | 1.545 | 0.000 | 1.545 | 1.545 |
| 179 | TYR | 258 | PHE | 1.362 | 2.902 | -1.540 | 1.540 |
| 176 | TYR | 180 | PHE | 1.965 | 3.496 | -1.531 | 1.531 |
| 135 | ILE | 180 | PHE | 2.867 | 1.339 | 1.528 | 1.528 |
| 168 | PHE | 172 | VAL | 3.905 | 2.388 | 1.517 | 1.517 |
| 183 | PHE | 258 | PHE | 0.000 | 1.511 | -1.511 | 1.511 |
| 150 | LYS | 153 | LYS | 1.739 | 0.240 | 1.499 | 1.499 |
| 62 | PHE | 84 | VAL | 1.495 | 0.000 | 1.495 | 1.495 |
| 204 | ALA | 225 | LEU | 2.290 | 0.797 | 1.493 | 1.493 |
| 144 | ASN | 146 | CYS | 1.835 | 3.322 | -1.486 | 1.486 |
| 135 | ILE | 176 | TYR | 4.010 | 2.530 | 1.480 | 1.480 |
| 47 | SER | 94 | SER | 0.619 | 2.088 | -1.470 | 1.470 |
| 238 | ILE | 287 | ILE | 0.000 | 1.455 | -1.455 | 1.455 |
| 44 | PHE | 125 | ILE | 1.392 | 2.828 | -1.436 | 1.436 |
| 9 | TYR | 274 | ILE | 2.039 | 0.617 | 1.421 | 1.421 |
| 186 | VAL | 242 | PHE | 1.416 | 0.000 | 1.416 | 1.416 |
| 27 | VAL | 285 | PRO | 0.000 | 1.410 | -1.410 | 1.410 |
| 27 | VAL | 288 | TYR | 0.000 | 1.405 | -1.405 | 1.405 |
| 44 | PHE | 94 | SER | 0.024 | 1.421 | -1.397 | 1.397 |
| 241 | LEU | 280 | ASN | 0.223 | 1.600 | -1.376 | 1.376 |
| 177 | MET | 181 | ASN | 1.919 | 0.544 | 1.375 | 1.375 |
| 179 | TYR | 183 | PHE | 0.048 | 1.380 | -1.332 | 1.332 |
| 55 | VAL | 87 | LEU | 1.467 | 2.797 | -1.330 | 1.330 |
| 145 | ASN | 173 | PRO | 6.499 | 5.173 | 1.325 | 1.325 |
| 307 | VAL | 311 | GLN | 1.323 | 0.000 | 1.323 | 1.323 |
| 48 | LEU | 98 | ILE | 1.314 | 0.000 | 1.314 | 1.314 |
| 45 | VAL | 285 | PRO | 1.313 | 0.000 | 1.313 | 1.313 |
| 211 | MET | 217 | PRO | 1.309 | 0.000 | 1.309 | 1.309 |
| 24 | ASN | 52 | ASP | 3.519 | 4.828 | -1.309 | 1.309 |
| 48 | LEU | 94 | SER | 3.349 | 2.058 | 1.291 | 1.291 |
| 154 | ASN | 163 | GLN | 2.826 | 1.537 | 1.288 | 1.288 |
| 81 | ALA | 168 | PHE | 1.506 | 2.793 | -1.288 | 1.288 |
| 52 | ASP | 285 | PRO | 1.287 | 0.000 | 1.287 | 1.287 |
| 186 | VAL | 250 | HIS | 3.300 | 2.017 | 1.284 | 1.284 |
| 137 | LEU | 140 | MET | 0.098 | 1.381 | -1.282 | 1.282 |
| 290 | TYR | 299 | PHE | 1.281 | 0.000 | 1.281 | 1.281 |
| 183 | PHE | 188 | VAL | 4.254 | 2.996 | 1.258 | 1.258 |
| 197 | TYR | 198 | LEU | 1.255 | 0.000 | 1.255 | 1.255 |
| 153 | LYS | 170 | ASP | 5.263 | 4.013 | 1.251 | 1.251 |
| 102 | ARG | 235 | LEU | 0.202 | 1.452 | -1.249 | 1.249 |
| 63 | ALA | 84 | VAL | 1.245 | 0.000 | 1.245 | 1.245 |
| 20 | ALA | 281 | SER | 1.070 | 2.309 | -1.239 | 1.239 |
| 238 | ILE | 288 | TYR | 1.516 | 2.755 | -1.238 | 1.238 |
| 58 | LEU | 87 | LEU | 1.238 | 0.000 | 1.238 | 1.238 |
| 157 | GLN | 165 | ALA | 0.681 | 1.916 | -1.235 | 1.235 |
| 49 | ALA | 285 | PRO | 1.224 | 0.000 | 1.224 | 1.224 |
| 101 | ASP | 112 | TYR | 6.036 | 4.816 | 1.221 | 1.221 |
| 26 | LEU | 299 | PHE | 5.336 | 6.547 | -1.211 | 1.211 |
| 106 | ILE | 200 | ILE | 2.142 | 0.958 | 1.184 | 1.184 |
| 88 | THR | 242 | PHE | 0.000 | 1.182 | -1.182 | 1.182 |
| 96 | LEU | 189 | PRO | 1.323 | 0.144 | 1.179 | 1.179 |
| 283 | VAL | 287 | ILE | 1.178 | 0.000 | 1.178 | 1.178 |
| 82 | CYS | 140 | MET | 1.175 | 0.000 | 1.175 | 1.175 |
| 75 | HIS | 146 | CYS | 1.477 | 0.303 | 1.174 | 1.174 |
| 143 | TRP | 176 | TYR | 7.700 | 6.541 | 1.159 | 1.159 |
| 197 | TYR | 239 | VAL | 0.204 | 1.358 | -1.154 | 1.154 |
| 86 | VAL | 133 | PHE | 3.902 | 5.053 | -1.151 | 1.151 |
| 272 | LEU | 276 | LEU | 1.146 | 0.000 | 1.146 | 1.146 |
| 86 | VAL | 132 | SER | 4.692 | 5.834 | -1.142 | 1.142 |
| 9 | TYR | 63 | ALA | 0.879 | 2.020 | -1.141 | 1.141 |
| 85 | LEU | 168 | PHE | 1.136 | 0.000 | 1.136 | 1.136 |
| 67 | SER | 271 | TYR | 0.876 | 2.012 | -1.136 | 1.136 |
| 314 | PHE | 316 | ALA | 0.000 | 1.134 | -1.134 | 1.134 |
| 190 | LEU | 247 | LEU | 1.132 | 0.000 | 1.132 | 1.132 |
| 93 | PHE | 184 | ALA | 1.120 | 0.000 | 1.120 | 1.120 |
| 24 | ASN | 49 | ALA | 6.371 | 5.255 | 1.116 | 1.116 |
| 200 | ILE | 235 | LEU | 1.114 | 0.000 | 1.114 | 1.114 |
| 6 | SER | 8 | VAL | 1.109 | 0.000 | 1.109 | 1.109 |
| 40 | VAL | 117 | THR | 0.584 | 1.681 | -1.097 | 1.097 |
| 184 | ALA | 189 | PRO | 2.278 | 1.184 | 1.094 | 1.094 |
| 380 | LEU | 381 | PRO | 0.210 | 1.291 | -1.082 | 1.082 |
| 79 | PHE | 83 | PHE | 0.054 | 1.135 | -1.081 | 1.081 |
| 106 | ILE | 231 | ALA | 1.076 | 0.000 | 1.076 | 1.076 |
| 37 | LEU | 295 | PHE | 5.042 | 3.974 | 1.068 | 1.068 |
| 182 | PHE | 187 | LEU | 4.657 | 3.594 | 1.064 | 1.064 |
| 96 | LEU | 192 | LEU | 1.267 | 0.218 | 1.050 | 1.050 |
| 95 | LEU | 242 | PHE | 0.887 | 1.936 | -1.048 | 1.048 |
| 366 | VAL | 367 | SER | 1.047 | 0.000 | 1.047 | 1.047 |
| 174 | MET | 257 | PHE | 1.891 | 2.923 | -1.032 | 1.032 |
| 183 | PHE | 187 | LEU | 1.345 | 0.333 | 1.012 | 1.012 |
| 59 | ALA | 84 | VAL | 2.057 | 1.066 | 0.991 | 0.991 |
| 44 | PHE | 98 | ILE | 2.913 | 1.927 | 0.986 | 0.986 |
| 45 | VAL | 98 | ILE | 1.952 | 0.968 | 0.983 | 0.983 |
| 111 | ARG | 115 | LEU | 0.000 | 0.983 | -0.983 | 0.983 |
| 304 | ARG | 308 | LEU | 1.021 | 0.051 | 0.970 | 0.970 |
| 79 | PHE | 140 | MET | 1.913 | 2.883 | -0.970 | 0.970 |
| 3 | ILE | 167 | LEU | 0.967 | 0.000 | 0.967 | 0.967 |
| 52 | ASP | 281 | SER | 10.660 | 11.626 | -0.966 | 0.966 |
| 71 | CYS | 163 | GLN | 2.114 | 1.149 | 0.965 | 0.965 |
| 284 | ASN | 285 | PRO | 0.000 | 0.964 | -0.964 | 0.964 |
| 95 | LEU | 239 | VAL | 0.000 | 0.953 | -0.953 | 0.953 |
| 138 | THR | 180 | PHE | 1.989 | 1.039 | 0.950 | 0.950 |
| 99 | ALA | 235 | LEU | 0.950 | 0.000 | 0.950 | 0.950 |
| 92 | ILE | 242 | PHE | 1.796 | 2.731 | -0.935 | 0.935 |
| 129 | TRP | 133 | PHE | 1.349 | 0.416 | 0.933 | 0.933 |
| 13 | GLU | 274 | ILE | 2.153 | 1.223 | 0.930 | 0.930 |
| 182 | PHE | 247 | LEU | 0.167 | 1.096 | -0.930 | 0.930 |
| 66 | ILE | 80 | ILE | 2.274 | 3.201 | -0.928 | 0.928 |
| 112 | TYR | 116 | VAL | 3.190 | 4.117 | -0.927 | 0.927 |
| 21 | ILE | 56 | GLY | 1.431 | 2.352 | -0.921 | 0.921 |
| 302 | ILE | 307 | VAL | 0.000 | 0.918 | -0.918 | 0.918 |
| 38 | GLN | 43 | TYR | 0.000 | 0.905 | -0.905 | 0.905 |
| 334 | VAL | 335 | SER | 1.082 | 1.984 | -0.901 | 0.901 |
| 405 | ALA | 406 | GLN | 0.000 | 0.900 | -0.900 | 0.900 |
| 305 | SER | 310 | GLN | 0.000 | 0.880 | -0.880 | 0.880 |
| 246 | TRP | 277 | SER | 3.733 | 4.601 | -0.868 | 0.868 |
| 94 | SER | 128 | CYS | 0.866 | 0.000 | 0.866 | 0.866 |
| 200 | ILE | 232 | ALA | 1.304 | 0.439 | 0.866 | 0.866 |
| 89 | GLN | 92 | ILE | 0.000 | 0.865 | -0.865 | 0.865 |
| 85 | LEU | 136 | GLY | 0.952 | 1.816 | -0.864 | 0.864 |
| 91 | SER | 281 | SER | 0.861 | 0.000 | 0.861 | 0.861 |
| 117 | THR | 120 | ARG | 1.897 | 2.750 | -0.853 | 0.853 |
| 69 | GLY | 166 | CYS | 4.565 | 3.714 | 0.851 | 0.851 |
| 354 | PRO | 355 | GLU | 0.848 | 0.000 | 0.848 | 0.848 |
| 95 | LEU | 238 | ILE | 1.520 | 0.679 | 0.841 | 0.841 |
| 114 | GLY | 120 | ARG | 1.159 | 1.996 | -0.837 | 0.837 |
| 42 | ASN | 295 | PHE | 3.135 | 2.301 | 0.834 | 0.834 |
| 74 | CYS | 146 | CYS | 7.423 | 6.590 | 0.833 | 0.833 |
| 238 | ILE | 284 | ASN | 2.412 | 1.581 | 0.831 | 0.831 |
| 404 | LEU | 405 | ALA | 0.000 | 0.830 | -0.830 | 0.830 |
| 89 | GLN | 135 | ILE | 2.131 | 2.957 | -0.826 | 0.826 |
| 403 | PRO | 404 | LEU | 1.263 | 0.436 | 0.826 | 0.826 |
| 182 | PHE | 186 | VAL | 1.423 | 0.628 | 0.795 | 0.795 |
| 78 | LEU | 146 | CYS | 0.374 | 1.166 | -0.793 | 0.793 |
| 48 | LEU | 284 | ASN | 0.407 | 1.199 | -0.792 | 0.792 |
| 197 | TYR | 200 | ILE | 0.000 | 0.787 | -0.787 | 0.787 |
| 106 | ILE | 228 | GLU | 1.648 | 0.862 | 0.786 | 0.786 |
| 201 | PHE | 236 | ALA | 0.000 | 0.782 | -0.782 | 0.782 |
| 182 | PHE | 254 | CYS | 0.675 | 1.454 | -0.779 | 0.779 |
| 55 | VAL | 60 | ILE | 4.303 | 5.076 | -0.773 | 0.773 |
| 103 | TYR | 107 | ARG | 2.497 | 3.268 | -0.771 | 0.771 |
| 249 | LEU | 277 | SER | 0.899 | 0.130 | 0.768 | 0.768 |
| 93 | PHE | 185 | CYS | 0.766 | 0.000 | 0.766 | 0.766 |
| 282 | VAL | 286 | PHE | 0.000 | 0.761 | -0.761 | 0.761 |
| 346 | TRP | 347 | ALA | 0.000 | 0.757 | -0.757 | 0.757 |
| 43 | TYR | 125 | ILE | 1.256 | 2.005 | -0.750 | 0.750 |
| 234 | SER | 288 | TYR | 0.749 | 0.000 | 0.749 | 0.749 |
| 6 | SER | 9 | TYR | 0.740 | 0.000 | 0.740 | 0.740 |
| 29 | TRP | 33 | LEU | 3.579 | 4.315 | -0.736 | 0.736 |
| 40 | VAL | 101 | ASP | 0.000 | 0.736 | -0.736 | 0.736 |
| 181 | ASN | 185 | CYS | 0.730 | 0.000 | 0.730 | 0.730 |
| 16 | ILE | 275 | VAL | 2.152 | 1.424 | 0.727 | 0.727 |
| 48 | LEU | 91 | SER | 3.515 | 2.790 | 0.725 | 0.725 |
| 139 | PRO | 176 | TYR | 6.156 | 6.876 | -0.720 | 0.720 |
| 285 | PRO | 299 | PHE | 0.000 | 0.711 | -0.711 | 0.711 |
| 32 | TRP | 38 | GLN | 1.541 | 2.250 | -0.709 | 0.709 |
| 230 | HIS | 234 | SER | 1.737 | 1.030 | 0.707 | 0.707 |
| 31 | VAL | 38 | GLN | 2.446 | 3.142 | -0.695 | 0.695 |
| 186 | VAL | 190 | LEU | 0.000 | 0.692 | -0.692 | 0.692 |
| 27 | VAL | 286 | PHE | 0.691 | 0.000 | 0.691 | 0.691 |
| 55 | VAL | 88 | THR | 0.689 | 0.000 | 0.689 | 0.689 |
| 230 | HIS | 291 | ARG | 3.260 | 2.573 | 0.687 | 0.687 |
| 246 | TRP | 250 | HIS | 1.637 | 0.950 | 0.687 | 0.687 |
| 20 | ALA | 282 | VAL | 2.343 | 1.658 | 0.685 | 0.685 |
| 406 | GLN | 407 | ASP | 1.349 | 0.664 | 0.685 | 0.685 |
| 66 | ILE | 166 | CYS | 3.074 | 3.759 | -0.684 | 0.684 |
| 5 | GLY | 271 | TYR | 0.674 | 0.000 | 0.674 | 0.674 |
| 190 | LEU | 193 | MET | 0.000 | 0.672 | -0.672 | 0.672 |
| 99 | ALA | 200 | ILE | 0.000 | 0.664 | -0.664 | 0.664 |
| 197 | TYR | 232 | ALA | 2.320 | 1.659 | 0.661 | 0.661 |
| 284 | ASN | 288 | TYR | 0.000 | 0.653 | -0.653 | 0.653 |
| 143 | TRP | 180 | PHE | 0.760 | 1.411 | -0.651 | 0.651 |
| 99 | ALA | 193 | MET | 0.976 | 0.325 | 0.651 | 0.651 |
| 200 | ILE | 228 | GLU | 0.645 | 0.000 | 0.645 | 0.645 |
| 62 | PHE | 79 | PHE | 0.000 | 0.643 | -0.643 | 0.643 |
| 268 | TRP | 269 | LEU | 2.878 | 3.508 | -0.630 | 0.630 |
| 78 | LEU | 171 | VAL | 3.785 | 3.162 | 0.624 | 0.624 |
| 40 | VAL | 116 | VAL | 2.181 | 2.804 | -0.623 | 0.623 |
| 196 | VAL | 235 | LEU | 0.621 | 0.000 | 0.621 | 0.621 |
| 208 | LEU | 222 | ARG | 0.000 | 0.618 | -0.618 | 0.618 |
| 149 | PRO | 154 | ASN | 0.096 | 0.712 | -0.616 | 0.616 |
| 249 | LEU | 274 | ILE | 0.972 | 0.359 | 0.613 | 0.613 |
| 145 | ASN | 172 | VAL | 1.722 | 1.111 | 0.610 | 0.610 |
| 237 | ILE | 291 | ARG | 2.667 | 2.063 | 0.603 | 0.603 |
| 371 | ALA | 372 | GLN | 0.269 | 0.870 | -0.601 | 0.601 |
| 44 | PHE | 116 | VAL | 0.591 | 0.000 | 0.591 | 0.591 |
| 125 | ILE | 129 | TRP | 0.592 | 1.182 | -0.590 | 0.590 |
| 245 | CYS | 276 | LEU | 6.879 | 6.293 | 0.586 | 0.586 |
| 83 | PHE | 87 | LEU | 2.595 | 2.014 | 0.581 | 0.581 |
| 24 | ASN | 53 | ILE | 2.301 | 2.876 | -0.576 | 0.576 |
| 99 | ALA | 196 | VAL | 1.770 | 2.345 | -0.575 | 0.575 |
| 353 | HIS | 354 | PRO | 0.000 | 0.564 | -0.564 | 0.564 |
| 107 | ARG | 199 | ARG | 0.564 | 0.000 | 0.564 | 0.564 |
| 178 | VAL | 254 | CYS | 2.046 | 1.482 | 0.564 | 0.564 |
| 77 | CYS | 171 | VAL | 2.189 | 1.628 | 0.561 | 0.561 |
| 98 | ILE | 288 | TYR | 0.560 | 0.000 | 0.560 | 0.560 |
| 183 | PHE | 254 | CYS | 0.000 | 0.552 | -0.552 | 0.552 |
| 48 | LEU | 288 | TYR | 0.000 | 0.551 | -0.551 | 0.551 |
| 102 | ARG | 112 | TYR | 1.367 | 1.918 | -0.551 | 0.551 |
| 234 | SER | 287 | ILE | 0.000 | 0.548 | -0.548 | 0.548 |
| 9 | TYR | 13 | GLU | 6.327 | 6.872 | -0.545 | 0.545 |
| 145 | ASN | 169 | GLU | 1.154 | 0.611 | 0.543 | 0.543 |
| 51 | ALA | 91 | SER | 1.314 | 0.772 | 0.542 | 0.542 |
| 13 | GLU | 64 | ILE | 1.434 | 0.896 | 0.538 | 0.538 |
| 224 | THR | 228 | GLU | 0.537 | 0.000 | 0.537 | 0.537 |
| 79 | PHE | 137 | LEU | 0.000 | 0.534 | -0.534 | 0.534 |
| 92 | ILE | 193 | MET | 0.000 | 0.528 | -0.528 | 0.528 |
| 208 | LEU | 225 | LEU | 1.769 | 2.291 | -0.522 | 0.522 |
| 193 | MET | 239 | VAL | 2.287 | 1.765 | 0.522 | 0.522 |
| 41 | THR | 98 | ILE | 0.000 | 0.520 | -0.520 | 0.520 |
| 135 | ILE | 184 | ALA | 0.519 | 0.000 | 0.519 | 0.519 |
| 40 | VAL | 44 | PHE | 0.256 | 0.773 | -0.517 | 0.517 |
| 37 | LEU | 42 | ASN | 6.200 | 6.717 | -0.517 | 0.517 |
| 101 | ASP | 102 | ARG | 5.183 | 5.699 | -0.516 | 0.516 |
| 78 | LEU | 139 | PRO | 1.448 | 0.937 | 0.510 | 0.510 |
| 241 | LEU | 283 | VAL | 1.033 | 0.524 | 0.509 | 0.509 |
| 14 | LEU | 64 | ILE | 1.314 | 0.806 | 0.508 | 0.508 |
| 1 | MET | 2 | PRO | 0.756 | 1.263 | -0.507 | 0.507 |
| 215 | PRO | 216 | LEU | 0.000 | 0.503 | -0.503 | 0.503 |
| 82 | CYS | 172 | VAL | 0.000 | 0.500 | -0.500 | 0.500 |
| 75 | HIS | 140 | MET | 0.314 | 0.812 | -0.498 | 0.498 |
| 29 | TRP | 32 | TRP | 1.211 | 0.719 | 0.492 | 0.492 |
| 181 | ASN | 250 | HIS | 1.275 | 1.761 | -0.485 | 0.485 |
| 84 | VAL | 85 | LEU | 0.000 | 0.481 | -0.481 | 0.481 |
| 102 | ARG | 200 | ILE | 0.841 | 1.320 | -0.478 | 0.478 |
| 400 | LEU | 401 | ASP | 0.000 | 0.477 | -0.477 | 0.477 |
| 97 | ALA | 124 | ILE | 0.472 | 0.000 | 0.472 | 0.472 |
| 17 | ALA | 56 | GLY | 2.561 | 3.034 | -0.472 | 0.472 |
| 386 | LEU | 388 | HIS | 0.472 | 0.000 | 0.472 | 0.472 |
| 135 | ILE | 181 | ASN | 0.464 | 0.000 | 0.464 | 0.464 |
| 190 | LEU | 239 | VAL | 0.874 | 0.411 | 0.463 | 0.463 |
| 39 | ASN | 41 | THR | 1.963 | 1.500 | 0.462 | 0.462 |
| 145 | ASN | 171 | VAL | 4.878 | 4.429 | 0.448 | 0.448 |
| 40 | VAL | 118 | GLY | 0.685 | 1.131 | -0.446 | 0.446 |
| 308 | LEU | 310 | GLN | 0.000 | 0.445 | -0.445 | 0.445 |
| 63 | ALA | 278 | HIS | 1.273 | 0.829 | 0.444 | 0.444 |
| 96 | LEU | 100 | ILE | 1.362 | 0.920 | 0.441 | 0.441 |
| 62 | PHE | 83 | PHE | 2.042 | 2.483 | -0.440 | 0.440 |
| 85 | LEU | 181 | ASN | 1.340 | 1.779 | -0.439 | 0.439 |
| 245 | CYS | 277 | SER | 3.508 | 3.071 | 0.437 | 0.437 |
| 44 | PHE | 124 | ILE | 1.419 | 0.985 | 0.434 | 0.434 |
| 89 | GLN | 132 | SER | 5.710 | 5.277 | 0.433 | 0.433 |
| 82 | CYS | 139 | PRO | 1.803 | 1.372 | 0.431 | 0.431 |
| 254 | CYS | 258 | PHE | 0.680 | 1.111 | -0.431 | 0.431 |
| 30 | ALA | 37 | LEU | 1.541 | 1.969 | -0.428 | 0.428 |
| 91 | SER | 242 | PHE | 0.000 | 0.428 | -0.428 | 0.428 |
| 225 | LEU | 229 | VAL | 0.883 | 0.460 | 0.423 | 0.423 |
| 178 | VAL | 258 | PHE | 1.095 | 1.516 | -0.421 | 0.421 |
| 105 | ALA | 112 | TYR | 5.215 | 4.797 | 0.418 | 0.418 |
| 204 | ALA | 229 | VAL | 0.514 | 0.932 | -0.418 | 0.418 |
| 396 | GLU | 397 | PRO | 0.759 | 1.175 | -0.416 | 0.416 |
| 266 | PRO | 268 | TRP | 3.985 | 4.398 | -0.413 | 0.413 |
| 104 | ILE | 115 | LEU | 0.636 | 0.226 | 0.411 | 0.411 |
| 78 | LEU | 82 | CYS | 0.604 | 0.195 | 0.409 | 0.409 |
| 54 | ALA | 59 | ALA | 1.286 | 1.693 | -0.408 | 0.408 |
| 92 | ILE | 189 | PRO | 0.932 | 1.338 | -0.406 | 0.406 |
| 345 | VAL | 347 | ALA | 0.403 | 0.000 | 0.403 | 0.403 |
| 164 | VAL | 171 | VAL | 0.000 | 0.403 | -0.403 | 0.403 |
| 302 | ILE | 306 | HIS | 0.000 | 0.401 | -0.401 | 0.401 |
| 93 | PHE | 189 | PRO | 0.400 | 0.000 | 0.400 | 0.400 |
| 242 | PHE | 284 | ASN | 0.400 | 0.000 | 0.400 | 0.400 |
| 84 | VAL | 246 | TRP | 0.000 | 0.396 | -0.396 | 0.396 |
| 177 | MET | 250 | HIS | 0.396 | 0.001 | 0.395 | 0.395 |
| 16 | ILE | 278 | HIS | 1.586 | 1.977 | -0.391 | 0.391 |
| 27 | VAL | 289 | ALA | 0.385 | 0.000 | 0.385 | 0.385 |
| 190 | LEU | 243 | ALA | 1.118 | 0.735 | 0.383 | 0.383 |
| 402 | ASP | 403 | PRO | 1.847 | 1.464 | 0.383 | 0.383 |
| 74 | CYS | 171 | VAL | 0.967 | 0.589 | 0.379 | 0.379 |
| 90 | SER | 132 | SER | 4.224 | 4.602 | -0.378 | 0.378 |
| 72 | ALA | 77 | CYS | 0.009 | 0.387 | -0.378 | 0.378 |
| 66 | ILE | 84 | VAL | 0.377 | 0.000 | 0.377 | 0.377 |
| 167 | LEU | 170 | ASP | 2.605 | 2.229 | 0.376 | 0.376 |
| 100 | ILE | 196 | VAL | 0.000 | 0.373 | -0.373 | 0.373 |
| 241 | LEU | 284 | ASN | 0.373 | 0.000 | 0.373 | 0.373 |
| 41 | THR | 288 | TYR | 0.373 | 0.000 | 0.373 | 0.373 |
| 21 | ILE | 53 | ILE | 0.357 | 0.728 | -0.371 | 0.371 |
| 248 | PRO | 273 | ALA | 0.564 | 0.193 | 0.371 | 0.371 |
| 71 | CYS | 157 | GLN | 0.820 | 0.450 | 0.370 | 0.370 |
| 243 | ALA | 248 | PRO | 0.563 | 0.195 | 0.367 | 0.367 |
| 193 | MET | 238 | ILE | 0.367 | 0.000 | 0.367 | 0.367 |
| 98 | ILE | 197 | TYR | 0.000 | 0.366 | -0.366 | 0.366 |
| 274 | ILE | 278 | HIS | 1.622 | 1.983 | -0.361 | 0.361 |
| 370 | SER | 371 | ALA | 0.000 | 0.358 | -0.358 | 0.358 |
| 31 | VAL | 42 | ASN | 0.250 | 0.609 | -0.358 | 0.358 |
| 31 | VAL | 295 | PHE | 1.549 | 1.194 | 0.355 | 0.355 |
| 165 | ALA | 170 | ASP | 0.386 | 0.033 | 0.353 | 0.353 |
| 185 | CYS | 242 | PHE | 0.351 | 0.000 | 0.351 | 0.351 |
| 106 | ILE | 232 | ALA | 0.000 | 0.349 | -0.349 | 0.349 |
| 93 | PHE | 128 | CYS | 4.594 | 4.943 | -0.348 | 0.348 |
| 55 | VAL | 59 | ALA | 0.762 | 0.414 | 0.348 | 0.348 |
| 71 | CYS | 159 | CYS | 6.921 | 6.573 | 0.348 | 0.348 |
| 372 | GLN | 373 | GLU | 0.347 | 0.000 | 0.347 | 0.347 |
| 67 | SER | 167 | LEU | 0.346 | 0.000 | 0.346 | 0.346 |
| 248 | PRO | 276 | LEU | 0.424 | 0.770 | -0.346 | 0.346 |
| 335 | SER | 336 | LEU | 0.000 | 0.345 | -0.345 | 0.345 |
| 88 | THR | 92 | ILE | 0.000 | 0.344 | -0.344 | 0.344 |
| 144 | ASN | 173 | PRO | 3.414 | 3.071 | 0.343 | 0.343 |
| 82 | CYS | 137 | LEU | 0.647 | 0.990 | -0.342 | 0.342 |
| 136 | GLY | 176 | TYR | 1.867 | 2.208 | -0.341 | 0.341 |
| 124 | ILE | 128 | CYS | 0.168 | 0.509 | -0.341 | 0.341 |
| 172 | VAL | 176 | TYR | 1.095 | 0.755 | 0.340 | 0.340 |
| 208 | LEU | 226 | GLN | 0.000 | 0.338 | -0.338 | 0.338 |
| 133 | PHE | 137 | LEU | 0.874 | 0.538 | 0.337 | 0.337 |
| 213 | SER | 214 | GLN | 0.335 | 0.000 | 0.335 | 0.335 |
| 205 | ARG | 209 | LYS | 0.335 | 0.000 | 0.335 | 0.335 |
| 244 | LEU | 276 | LEU | 0.888 | 0.556 | 0.332 | 0.332 |
| 194 | LEU | 197 | TYR | 0.332 | 0.000 | 0.332 | 0.332 |
| 157 | GLN | 159 | CYS | 0.609 | 0.277 | 0.332 | 0.332 |
| 41 | THR | 42 | ASN | 0.369 | 0.048 | 0.322 | 0.322 |
| 94 | SER | 125 | ILE | 0.319 | 0.000 | 0.319 | 0.319 |
| 151 | GLU | 155 | HIS | 0.000 | 0.315 | -0.315 | 0.315 |
| 77 | CYS | 167 | LEU | 0.672 | 0.360 | 0.312 | 0.312 |
| 112 | TYR | 113 | ASN | 1.468 | 1.778 | -0.310 | 0.310 |
| 280 | ASN | 283 | VAL | 0.025 | 0.333 | -0.308 | 0.308 |
| 397 | PRO | 398 | PRO | 0.704 | 0.398 | 0.306 | 0.306 |
| 66 | ILE | 81 | ALA | 2.212 | 2.517 | -0.305 | 0.305 |
| 251 | ILE | 255 | PHE | 1.486 | 1.183 | 0.303 | 0.303 |
| 292 | ILE | 294 | GLU | 0.956 | 0.654 | 0.302 | 0.302 |
| 194 | LEU | 198 | LEU | 0.729 | 1.027 | -0.298 | 0.298 |
| 12 | VAL | 16 | ILE | 0.271 | 0.569 | -0.298 | 0.298 |
| 241 | LEU | 287 | ILE | 0.711 | 1.006 | -0.295 | 0.295 |
| 197 | TYR | 201 | PHE | 1.320 | 1.028 | 0.292 | 0.292 |
| 143 | TRP | 173 | PRO | 4.243 | 3.952 | 0.291 | 0.291 |
| 355 | GLU | 356 | ARG | 0.286 | 0.000 | 0.286 | 0.286 |
| 356 | ARG | 357 | ARG | 0.285 | 0.000 | 0.285 | 0.285 |
| 287 | ILE | 292 | ILE | 0.000 | 0.282 | -0.282 | 0.282 |
| 69 | GLY | 165 | ALA | 1.939 | 1.657 | 0.282 | 0.282 |
| 10 | ILE | 64 | ILE | 0.831 | 1.113 | -0.282 | 0.282 |
| 74 | CYS | 164 | VAL | 2.134 | 1.854 | 0.280 | 0.280 |
| 237 | ILE | 241 | LEU | 1.020 | 0.744 | 0.276 | 0.276 |
| 40 | VAL | 112 | TYR | 0.015 | 0.288 | -0.273 | 0.273 |
| 91 | SER | 280 | ASN | 0.271 | 0.000 | 0.271 | 0.271 |
| 41 | THR | 235 | LEU | 0.000 | 0.270 | -0.270 | 0.270 |
| 75 | HIS | 144 | ASN | 0.000 | 0.270 | -0.270 | 0.270 |
| 31 | VAL | 37 | LEU | 2.027 | 2.296 | -0.269 | 0.269 |
| 211 | MET | 222 | ARG | 0.865 | 1.125 | -0.260 | 0.260 |
| 69 | GLY | 167 | LEU | 1.558 | 1.299 | 0.260 | 0.260 |
| 71 | CYS | 158 | GLY | 0.644 | 0.388 | 0.256 | 0.256 |
| 98 | ILE | 285 | PRO | 0.255 | 0.000 | 0.255 | 0.255 |
| 216 | LEU | 217 | PRO | 0.148 | 0.400 | -0.252 | 0.252 |
| 312 | GLU | 313 | PRO | 0.141 | 0.393 | -0.251 | 0.251 |
| 52 | ASP | 284 | ASN | 2.485 | 2.736 | -0.251 | 0.251 |
| 250 | HIS | 253 | ASN | 0.299 | 0.049 | 0.250 | 0.250 |
| 72 | ALA | 164 | VAL | 6.713 | 6.466 | 0.247 | 0.247 |
| 37 | LEU | 294 | GLU | 0.968 | 1.214 | -0.246 | 0.246 |
| 183 | PHE | 189 | PRO | 0.246 | 0.000 | 0.246 | 0.246 |
| 83 | PHE | 137 | LEU | 0.000 | 0.245 | -0.245 | 0.245 |
| 100 | ILE | 104 | ILE | 0.524 | 0.769 | -0.245 | 0.245 |
| 26 | LEU | 303 | ILE | 0.376 | 0.132 | 0.244 | 0.244 |
| 101 | ASP | 116 | VAL | 0.692 | 0.936 | -0.244 | 0.244 |
| 168 | PHE | 169 | GLU | 0.005 | 0.247 | -0.242 | 0.242 |
| 50 | ALA | 129 | TRP | 0.000 | 0.240 | -0.240 | 0.240 |
| 72 | ALA | 166 | CYS | 0.104 | 0.342 | -0.238 | 0.238 |
| 186 | VAL | 247 | LEU | 0.237 | 0.000 | 0.237 | 0.237 |
| 55 | VAL | 278 | HIS | 0.000 | 0.237 | -0.237 | 0.237 |
| 245 | CYS | 279 | THR | 0.236 | 0.000 | 0.236 | 0.236 |
| 74 | CYS | 162 | GLY | 0.000 | 0.235 | -0.235 | 0.235 |
| 200 | ILE | 231 | ALA | 0.230 | 0.000 | 0.230 | 0.230 |
| 292 | ILE | 295 | PHE | 1.835 | 2.064 | -0.228 | 0.228 |
| 55 | VAL | 281 | SER | 2.652 | 2.880 | -0.228 | 0.228 |
| 249 | LEU | 253 | ASN | 0.342 | 0.115 | 0.227 | 0.227 |
| 68 | THR | 157 | GLN | 0.322 | 0.549 | -0.227 | 0.227 |
| 138 | THR | 176 | TYR | 1.501 | 1.728 | -0.227 | 0.227 |
| 176 | TYR | 177 | MET | 1.539 | 1.313 | 0.226 | 0.226 |
| 247 | LEU | 251 | ILE | 0.495 | 0.269 | 0.225 | 0.225 |
| 95 | LEU | 280 | ASN | 0.225 | 0.000 | 0.225 | 0.225 |
| 34 | ASN | 298 | THR | 3.078 | 3.302 | -0.224 | 0.224 |
| 108 | ILE | 111 | ARG | 1.644 | 1.420 | 0.224 | 0.224 |
| 21 | ILE | 57 | VAL | 1.935 | 2.158 | -0.223 | 0.223 |
| 288 | TYR | 292 | ILE | 0.975 | 0.752 | 0.223 | 0.223 |
| 85 | LEU | 177 | MET | 0.810 | 1.033 | -0.222 | 0.222 |
| 20 | ALA | 56 | GLY | 0.222 | 0.000 | 0.222 | 0.222 |
| 26 | LEU | 286 | PHE | 0.220 | 0.000 | 0.220 | 0.220 |
| 13 | GLU | 278 | HIS | 6.360 | 6.579 | -0.219 | 0.219 |
| 169 | GLU | 174 | MET | 0.849 | 1.068 | -0.218 | 0.218 |
| 16 | ILE | 60 | ILE | 0.957 | 1.174 | -0.218 | 0.218 |
| 83 | PHE | 133 | PHE | 0.000 | 0.216 | -0.216 | 0.216 |
| 16 | ILE | 282 | VAL | 1.851 | 2.066 | -0.215 | 0.215 |
| 265 | ALA | 270 | MET | 0.802 | 1.016 | -0.214 | 0.214 |
| 24 | ASN | 281 | SER | 2.104 | 2.314 | -0.210 | 0.210 |
| 187 | LEU | 191 | LEU | 1.087 | 0.877 | 0.210 | 0.210 |
| 10 | ILE | 14 | LEU | 0.603 | 0.813 | -0.210 | 0.210 |
| 264 | HIS | 265 | ALA | 0.000 | 0.210 | -0.210 | 0.210 |
| 298 | THR | 302 | ILE | 0.501 | 0.711 | -0.210 | 0.210 |
| 19 | LEU | 282 | VAL | 1.883 | 1.675 | 0.207 | 0.207 |
| 70 | PHE | 164 | VAL | 1.178 | 0.972 | 0.205 | 0.205 |
| 237 | ILE | 287 | ILE | 0.536 | 0.330 | 0.205 | 0.205 |
| 30 | ALA | 298 | THR | 2.490 | 2.695 | -0.205 | 0.205 |
| 214 | GLN | 215 | PRO | 0.592 | 0.387 | 0.205 | 0.205 |
| 68 | THR | 70 | PHE | 1.527 | 1.732 | -0.204 | 0.204 |
| 174 | MET | 177 | MET | 1.071 | 0.867 | 0.204 | 0.204 |
| 201 | PHE | 229 | VAL | 0.000 | 0.202 | -0.202 | 0.202 |
| 336 | LEU | 338 | LEU | 0.199 | 0.000 | 0.199 | 0.199 |
| 58 | LEU | 62 | PHE | 0.573 | 0.377 | 0.197 | 0.197 |
| 89 | GLN | 176 | TYR | 0.195 | 0.000 | 0.195 | 0.195 |
| 358 | PRO | 359 | ASN | 0.194 | 0.000 | 0.194 | 0.194 |
| 338 | LEU | 339 | ASN | 0.193 | 0.000 | 0.193 | 0.193 |
| 42 | ASN | 45 | VAL | 0.574 | 0.767 | -0.193 | 0.193 |
| 159 | CYS | 163 | GLN | 0.755 | 0.563 | 0.192 | 0.192 |
| 81 | ALA | 172 | VAL | 0.669 | 0.477 | 0.191 | 0.191 |
| 82 | CYS | 85 | LEU | 0.000 | 0.190 | -0.190 | 0.190 |
| 7 | SER | 8 | VAL | 0.190 | 0.000 | 0.190 | 0.190 |
| 34 | ASN | 37 | LEU | 2.347 | 2.537 | -0.190 | 0.190 |
| 177 | MET | 253 | ASN | 0.688 | 0.876 | -0.188 | 0.188 |
| 303 | ILE | 307 | VAL | 0.339 | 0.152 | 0.188 | 0.188 |
| 24 | ASN | 27 | VAL | 0.000 | 0.186 | -0.186 | 0.186 |
| 342 | PRO | 343 | PRO | 0.844 | 0.659 | 0.185 | 0.185 |
| 169 | GLU | 270 | MET | 0.945 | 0.763 | 0.182 | 0.182 |
| 104 | ILE | 112 | TYR | 1.392 | 1.211 | 0.181 | 0.181 |
| 243 | ALA | 247 | LEU | 0.685 | 0.505 | 0.181 | 0.181 |
| 117 | THR | 119 | THR | 0.390 | 0.210 | 0.180 | 0.180 |
| 17 | ALA | 60 | ILE | 2.660 | 2.839 | -0.179 | 0.179 |
| 86 | VAL | 137 | LEU | 1.264 | 1.442 | -0.178 | 0.178 |
| 70 | PHE | 72 | ALA | 1.497 | 1.674 | -0.177 | 0.177 |
| 249 | LEU | 270 | MET | 0.000 | 0.176 | -0.176 | 0.176 |
| 20 | ALA | 52 | ASP | 0.379 | 0.553 | -0.174 | 0.174 |
| 283 | VAL | 284 | ASN | 0.674 | 0.503 | 0.171 | 0.171 |
| 254 | CYS | 259 | CYS | 0.060 | 0.231 | -0.171 | 0.171 |
| 177 | MET | 182 | PHE | 3.313 | 3.144 | 0.169 | 0.169 |
| 27 | VAL | 49 | ALA | 0.574 | 0.743 | -0.168 | 0.168 |
| 84 | VAL | 278 | HIS | 0.019 | 0.187 | -0.168 | 0.168 |
| 188 | VAL | 192 | LEU | 0.691 | 0.524 | 0.167 | 0.167 |
| 178 | VAL | 179 | TYR | 0.000 | 0.167 | -0.167 | 0.167 |
| 295 | PHE | 299 | PHE | 2.368 | 2.202 | 0.166 | 0.166 |
| 144 | ASN | 171 | VAL | 1.850 | 1.685 | 0.165 | 0.165 |
| 97 | ALA | 128 | CYS | 0.165 | 0.000 | 0.165 | 0.165 |
| 55 | VAL | 91 | SER | 0.164 | 0.000 | 0.164 | 0.164 |
| 351 | ALA | 352 | PRO | 0.668 | 0.505 | 0.164 | 0.164 |
| 252 | ILE | 265 | ALA | 0.621 | 0.785 | -0.164 | 0.164 |
| 70 | PHE | 157 | GLN | 0.000 | 0.163 | -0.163 | 0.163 |
| 35 | SER | 38 | GLN | 0.000 | 0.160 | -0.160 | 0.160 |
| 266 | PRO | 269 | LEU | 1.362 | 1.203 | 0.160 | 0.160 |
| 277 | SER | 278 | HIS | 1.228 | 1.069 | 0.159 | 0.159 |
| 103 | TYR | 108 | ILE | 0.188 | 0.030 | 0.158 | 0.158 |
| 107 | ARG | 203 | ALA | 1.736 | 1.577 | 0.158 | 0.158 |
| 149 | PRO | 164 | VAL | 0.581 | 0.423 | 0.158 | 0.158 |
| 30 | ALA | 302 | ILE | 1.484 | 1.642 | -0.158 | 0.158 |
| 28 | CYS | 49 | ALA | 0.783 | 0.626 | 0.157 | 0.157 |
| 75 | HIS | 78 | LEU | 0.000 | 0.157 | -0.157 | 0.157 |
| 175 | ASN | 180 | PHE | 0.399 | 0.555 | -0.156 | 0.156 |
| 168 | PHE | 174 | MET | 0.267 | 0.423 | -0.156 | 0.156 |
| 184 | ALA | 185 | CYS | 0.271 | 0.119 | 0.153 | 0.153 |
| 28 | CYS | 50 | ALA | 0.153 | 0.000 | 0.153 | 0.153 |
| 314 | PHE | 317 | ALA | 0.152 | 0.000 | 0.152 | 0.152 |
| 291 | ARG | 292 | ILE | 0.000 | 0.152 | -0.152 | 0.152 |
| 288 | TYR | 296 | ARG | 0.000 | 0.152 | -0.152 | 0.152 |
| 37 | LEU | 298 | THR | 0.526 | 0.677 | -0.152 | 0.152 |
| 175 | ASN | 179 | TYR | 0.558 | 0.407 | 0.150 | 0.150 |
| 103 | TYR | 199 | ARG | 1.177 | 1.327 | -0.150 | 0.150 |
| 264 | HIS | 270 | MET | 0.000 | 0.150 | -0.150 | 0.150 |
| 78 | LEU | 172 | VAL | 0.371 | 0.519 | -0.148 | 0.148 |
| 73 | ALA | 163 | GLN | 0.020 | 0.167 | -0.147 | 0.147 |
| 33 | LEU | 306 | HIS | 0.000 | 0.146 | -0.146 | 0.146 |
| 47 | SER | 90 | SER | 0.000 | 0.146 | -0.146 | 0.146 |
| 154 | ASN | 165 | ALA | 2.448 | 2.304 | 0.144 | 0.144 |
| 153 | LYS | 156 | SER | 0.000 | 0.143 | -0.143 | 0.143 |
| 25 | VAL | 53 | ILE | 2.161 | 2.304 | -0.143 | 0.143 |
| 3 | ILE | 7 | SER | 0.000 | 0.142 | -0.142 | 0.142 |
| 288 | TYR | 299 | PHE | 0.000 | 0.142 | -0.142 | 0.142 |
| 70 | PHE | 165 | ALA | 1.080 | 0.940 | 0.141 | 0.141 |
| 31 | VAL | 46 | VAL | 1.877 | 1.737 | 0.140 | 0.140 |
| 88 | THR | 89 | GLN | 0.138 | 0.000 | 0.138 | 0.138 |
| 90 | SER | 94 | SER | 0.000 | 0.136 | -0.136 | 0.136 |
| 242 | PHE | 247 | LEU | 0.136 | 0.000 | 0.136 | 0.136 |
| 73 | ALA | 164 | VAL | 0.135 | 0.000 | 0.135 | 0.135 |
| 201 | PHE | 232 | ALA | 0.570 | 0.702 | -0.132 | 0.132 |
| 115 | LEU | 116 | VAL | 0.197 | 0.329 | -0.132 | 0.132 |
| 138 | THR | 143 | TRP | 1.225 | 1.094 | 0.130 | 0.130 |
| 81 | ALA | 171 | VAL | 0.381 | 0.251 | 0.130 | 0.130 |
| 287 | ILE | 291 | ARG | 0.222 | 0.351 | -0.128 | 0.128 |
| 179 | TYR | 257 | PHE | 4.710 | 4.584 | 0.126 | 0.126 |
| 60 | ILE | 61 | PRO | 1.304 | 1.430 | -0.126 | 0.126 |
| 9 | TYR | 275 | VAL | 1.110 | 0.986 | 0.125 | 0.125 |
| 93 | PHE | 132 | SER | 2.637 | 2.513 | 0.125 | 0.125 |
| 230 | HIS | 292 | ILE | 0.124 | 0.000 | 0.124 | 0.124 |
| 200 | ILE | 201 | PHE | 0.000 | 0.123 | -0.123 | 0.123 |
| 153 | LYS | 154 | ASN | 0.123 | 0.000 | 0.123 | 0.123 |
| 178 | VAL | 257 | PHE | 2.020 | 2.142 | -0.122 | 0.122 |
| 260 | PRO | 261 | ASP | 0.120 | 0.000 | 0.120 | 0.120 |
| 35 | SER | 36 | ASN | 0.244 | 0.124 | 0.120 | 0.120 |
| 66 | ILE | 77 | CYS | 0.000 | 0.117 | -0.117 | 0.117 |
| 249 | LEU | 250 | HIS | 0.116 | 0.000 | 0.116 | 0.116 |
| 2 | PRO | 4 | MET | 0.114 | 0.000 | 0.114 | 0.114 |
| 235 | LEU | 238 | ILE | 0.163 | 0.276 | -0.113 | 0.113 |
| 103 | TYR | 104 | ILE | 0.176 | 0.063 | 0.113 | 0.113 |
| 361 | TYR | 362 | ALA | 0.110 | 0.000 | 0.110 | 0.110 |
| 84 | VAL | 88 | THR | 0.113 | 0.223 | -0.110 | 0.110 |
| 107 | ARG | 108 | ILE | 0.357 | 0.467 | -0.110 | 0.110 |
| 3 | ILE | 67 | SER | 0.109 | 0.000 | 0.109 | 0.109 |
| 188 | VAL | 189 | PRO | 1.295 | 1.403 | -0.108 | 0.108 |
| 34 | ASN | 294 | GLU | 0.370 | 0.265 | 0.105 | 0.105 |
| 286 | PHE | 299 | PHE | 0.105 | 0.000 | 0.105 | 0.105 |
| 71 | CYS | 164 | VAL | 1.759 | 1.864 | -0.104 | 0.104 |
| 30 | ALA | 295 | PHE | 0.733 | 0.630 | 0.103 | 0.103 |
| 220 | ARG | 224 | THR | 0.103 | 0.000 | 0.103 | 0.103 |
| 235 | LEU | 288 | TYR | 0.000 | 0.101 | -0.101 | 0.101 |
| 189 | PRO | 242 | PHE | 0.099 | 0.000 | 0.099 | 0.099 |
| 92 | ILE | 93 | PHE | 0.098 | 0.000 | 0.098 | 0.098 |
| 106 | ILE | 225 | LEU | 0.000 | 0.096 | -0.096 | 0.096 |
| 241 | LEU | 244 | LEU | 0.000 | 0.095 | -0.095 | 0.095 |
| 139 | PRO | 144 | ASN | 4.087 | 4.182 | -0.094 | 0.094 |
| 172 | VAL | 177 | MET | 1.075 | 1.169 | -0.094 | 0.094 |
| 93 | PHE | 135 | ILE | 1.079 | 0.985 | 0.094 | 0.094 |
| 88 | THR | 278 | HIS | 0.093 | 0.000 | 0.093 | 0.093 |
| 286 | PHE | 290 | TYR | 0.047 | 0.139 | -0.092 | 0.092 |
| 173 | PRO | 176 | TYR | 0.357 | 0.266 | 0.092 | 0.092 |
| 65 | THR | 166 | CYS | 0.091 | 0.000 | 0.091 | 0.091 |
| 28 | CYS | 53 | ILE | 0.223 | 0.313 | -0.090 | 0.090 |
| 32 | TRP | 33 | LEU | 2.216 | 2.305 | -0.089 | 0.089 |
| 45 | VAL | 295 | PHE | 0.127 | 0.215 | -0.088 | 0.088 |
| 73 | ALA | 162 | GLY | 0.514 | 0.426 | 0.088 | 0.088 |
| 16 | ILE | 279 | THR | 2.146 | 2.233 | -0.087 | 0.087 |
| 259 | CYS | 262 | CYS | 3.578 | 3.664 | -0.086 | 0.086 |
| 77 | CYS | 166 | CYS | 6.949 | 7.035 | -0.086 | 0.086 |
| 64 | ILE | 67 | SER | 0.084 | 0.000 | 0.084 | 0.084 |
| 51 | ALA | 94 | SER | 0.083 | 0.000 | 0.083 | 0.083 |
| 104 | ILE | 109 | PRO | 0.498 | 0.415 | 0.083 | 0.083 |
| 275 | VAL | 279 | THR | 0.176 | 0.259 | -0.083 | 0.083 |
| 5 | GLY | 67 | SER | 0.081 | 0.000 | 0.081 | 0.081 |
| 207 | GLN | 211 | MET | 0.000 | 0.081 | -0.081 | 0.081 |
| 245 | CYS | 246 | TRP | 0.208 | 0.128 | 0.080 | 0.080 |
| 95 | LEU | 98 | ILE | 0.080 | 0.000 | 0.080 | 0.080 |
| 209 | LYS | 212 | GLU | 0.080 | 0.000 | 0.080 | 0.080 |
| 138 | THR | 139 | PRO | 1.066 | 0.988 | 0.078 | 0.078 |
| 97 | ALA | 125 | ILE | 0.077 | 0.000 | 0.077 | 0.077 |
| 145 | ASN | 170 | ASP | 3.225 | 3.148 | 0.077 | 0.077 |
| 81 | ALA | 82 | CYS | 0.000 | 0.076 | -0.076 | 0.076 |
| 40 | VAL | 121 | ALA | 0.787 | 0.863 | -0.076 | 0.076 |
| 53 | ILE | 57 | VAL | 0.376 | 0.452 | -0.076 | 0.076 |
| 252 | ILE | 270 | MET | 1.345 | 1.420 | -0.075 | 0.075 |
| 173 | PRO | 175 | ASN | 1.660 | 1.587 | 0.073 | 0.073 |
| 381 | PRO | 382 | ASP | 0.072 | 0.000 | 0.072 | 0.072 |
| 57 | VAL | 58 | LEU | 0.836 | 0.908 | -0.072 | 0.072 |
| 48 | LEU | 238 | ILE | 0.000 | 0.071 | -0.071 | 0.071 |
| 79 | PHE | 80 | ILE | 0.000 | 0.071 | -0.071 | 0.071 |
| 150 | LYS | 170 | ASP | 3.759 | 3.689 | 0.070 | 0.070 |
| 8 | VAL | 12 | VAL | 0.169 | 0.100 | 0.069 | 0.069 |
| 196 | VAL | 200 | ILE | 0.576 | 0.507 | 0.069 | 0.069 |
| 14 | LEU | 60 | ILE | 0.000 | 0.069 | -0.069 | 0.069 |
| 52 | ASP | 55 | VAL | 0.067 | 0.000 | 0.067 | 0.067 |
| 265 | ALA | 266 | PRO | 0.648 | 0.582 | 0.066 | 0.066 |
| 246 | TRP | 249 | LEU | 0.000 | 0.066 | -0.066 | 0.066 |
| 159 | CYS | 164 | VAL | 0.947 | 0.881 | 0.066 | 0.066 |
| 293 | ARG | 296 | ARG | 0.733 | 0.797 | -0.065 | 0.065 |
| 28 | CYS | 46 | VAL | 0.873 | 0.809 | 0.064 | 0.064 |
| 55 | VAL | 61 | PRO | 0.178 | 0.240 | -0.062 | 0.062 |
| 3 | ILE | 165 | ALA | 0.062 | 0.000 | 0.062 | 0.062 |
| 26 | LEU | 302 | ILE | 1.641 | 1.702 | -0.061 | 0.061 |
| 268 | TRP | 272 | LEU | 0.288 | 0.348 | -0.060 | 0.060 |
| 104 | ILE | 116 | VAL | 1.018 | 0.958 | 0.060 | 0.060 |
| 98 | ILE | 102 | ARG | 0.027 | 0.086 | -0.059 | 0.059 |
| 185 | CYS | 186 | VAL | 0.058 | 0.000 | 0.058 | 0.058 |
| 252 | ILE | 269 | LEU | 0.850 | 0.907 | -0.057 | 0.057 |
| 283 | VAL | 288 | TYR | 0.056 | 0.000 | 0.056 | 0.056 |
| 21 | ILE | 25 | VAL | 0.362 | 0.306 | 0.056 | 0.056 |
| 27 | VAL | 295 | PHE | 0.797 | 0.852 | -0.055 | 0.055 |
| 102 | ARG | 105 | ALA | 1.323 | 1.268 | 0.055 | 0.055 |
| 135 | ILE | 185 | CYS | 1.440 | 1.384 | 0.055 | 0.055 |
| 87 | LEU | 129 | TRP | 0.558 | 0.613 | -0.055 | 0.055 |
| 12 | VAL | 275 | VAL | 1.007 | 0.952 | 0.055 | 0.055 |
| 39 | ASN | 42 | ASN | 6.269 | 6.215 | 0.054 | 0.054 |
| 59 | ALA | 83 | PHE | 0.000 | 0.053 | -0.053 | 0.053 |
| 86 | VAL | 136 | GLY | 1.598 | 1.651 | -0.053 | 0.053 |
| 252 | ILE | 273 | ALA | 0.638 | 0.585 | 0.053 | 0.053 |
| 159 | CYS | 165 | ALA | 0.975 | 0.923 | 0.053 | 0.053 |
| 282 | VAL | 283 | VAL | 0.052 | 0.000 | 0.052 | 0.052 |
| 139 | PRO | 172 | VAL | 0.000 | 0.052 | -0.052 | 0.052 |
| 34 | ASN | 35 | SER | 0.159 | 0.109 | 0.050 | 0.050 |
| 175 | ASN | 176 | TYR | 0.285 | 0.334 | -0.050 | 0.050 |
| 171 | VAL | 172 | VAL | 0.435 | 0.485 | -0.049 | 0.049 |
| 193 | MET | 197 | TYR | 0.000 | 0.049 | -0.049 | 0.049 |
| 67 | SER | 68 | THR | 0.199 | 0.151 | 0.048 | 0.048 |
| 27 | VAL | 299 | PHE | 1.976 | 1.929 | 0.047 | 0.047 |
| 308 | LEU | 311 | GLN | 0.044 | 0.000 | 0.044 | 0.044 |
| 33 | LEU | 302 | ILE | 1.108 | 1.151 | -0.043 | 0.043 |
| 125 | ILE | 128 | CYS | 0.042 | 0.000 | 0.042 | 0.042 |
| 106 | ILE | 204 | ALA | 0.000 | 0.038 | -0.038 | 0.038 |
| 279 | THR | 283 | VAL | 0.189 | 0.150 | 0.038 | 0.038 |
| 85 | LEU | 176 | TYR | 1.409 | 1.447 | -0.038 | 0.038 |
| 18 | VAL | 22 | LEU | 0.889 | 0.851 | 0.038 | 0.038 |
| 9 | TYR | 10 | ILE | 0.245 | 0.283 | -0.038 | 0.038 |
| 30 | ALA | 299 | PHE | 1.476 | 1.439 | 0.036 | 0.036 |
| 178 | VAL | 253 | ASN | 1.574 | 1.608 | -0.034 | 0.034 |
| 9 | TYR | 64 | ILE | 0.483 | 0.517 | -0.033 | 0.033 |
| 233 | LYS | 237 | ILE | 0.074 | 0.106 | -0.032 | 0.032 |
| 301 | LYS | 306 | HIS | 0.000 | 0.031 | -0.031 | 0.031 |
| 175 | ASN | 257 | PHE | 3.598 | 3.629 | -0.031 | 0.031 |
| 54 | ALA | 83 | PHE | 0.000 | 0.029 | -0.029 | 0.029 |
| 72 | ALA | 163 | GLN | 3.914 | 3.885 | 0.029 | 0.029 |
| 27 | VAL | 45 | VAL | 0.665 | 0.637 | 0.027 | 0.027 |
| 247 | LEU | 248 | PRO | 0.739 | 0.766 | -0.027 | 0.027 |
| 189 | PRO | 193 | MET | 0.074 | 0.101 | -0.027 | 0.027 |
| 132 | SER | 137 | LEU | 0.097 | 0.072 | 0.025 | 0.025 |
| 290 | TYR | 291 | ARG | 0.000 | 0.023 | -0.023 | 0.023 |
| 127 | ILE | 131 | LEU | 0.804 | 0.827 | -0.023 | 0.023 |
| 153 | LYS | 165 | ALA | 0.023 | 0.000 | 0.023 | 0.023 |
| 393 | VAL | 395 | PRO | 0.000 | 0.023 | -0.023 | 0.023 |
| 245 | CYS | 280 | ASN | 3.011 | 3.033 | -0.022 | 0.022 |
| 174 | MET | 253 | ASN | 0.353 | 0.331 | 0.022 | 0.022 |
| 394 | CYS | 395 | PRO | 0.280 | 0.258 | 0.022 | 0.022 |
| 257 | PHE | 258 | PHE | 4.085 | 4.063 | 0.022 | 0.022 |
| 172 | VAL | 173 | PRO | 0.942 | 0.921 | 0.021 | 0.021 |
| 174 | MET | 256 | THR | 0.008 | 0.029 | -0.021 | 0.021 |
| 362 | ALA | 363 | LEU | 0.020 | 0.000 | 0.020 | 0.020 |
| 156 | SER | 157 | GLN | 0.058 | 0.078 | -0.020 | 0.020 |
| 45 | VAL | 289 | ALA | 0.020 | 0.000 | 0.020 | 0.020 |
| 148 | GLN | 149 | PRO | 0.110 | 0.091 | 0.019 | 0.019 |
| 70 | PHE | 80 | ILE | 0.553 | 0.535 | 0.019 | 0.019 |
| 56 | GLY | 61 | PRO | 1.426 | 1.442 | -0.016 | 0.016 |
| 133 | PHE | 138 | THR | 0.075 | 0.090 | -0.015 | 0.015 |
| 60 | ILE | 278 | HIS | 2.722 | 2.708 | 0.013 | 0.013 |
| 252 | ILE | 256 | THR | 0.412 | 0.400 | 0.013 | 0.013 |
| 271 | TYR | 274 | ILE | 0.044 | 0.031 | 0.013 | 0.013 |
| 78 | LEU | 144 | ASN | 3.198 | 3.186 | 0.011 | 0.011 |
| 326 | ALA | 327 | HIS | 0.011 | 0.000 | 0.011 | 0.011 |
| 108 | ILE | 109 | PRO | 0.076 | 0.087 | -0.011 | 0.011 |
| 20 | ALA | 53 | ILE | 0.005 | 0.015 | -0.010 | 0.010 |
| 146 | CYS | 171 | VAL | 0.010 | 0.000 | 0.010 | 0.010 |
| 72 | ALA | 162 | GLY | 0.135 | 0.126 | 0.009 | 0.009 |
| 20 | ALA | 24 | ASN | 0.136 | 0.128 | 0.008 | 0.008 |
| 153 | LYS | 167 | LEU | 0.130 | 0.123 | 0.007 | 0.007 |
| 2 | PRO | 156 | SER | 0.007 | 0.000 | 0.007 | 0.007 |
| 93 | PHE | 131 | LEU | 1.455 | 1.462 | -0.006 | 0.006 |
| 168 | PHE | 177 | MET | 2.832 | 2.838 | -0.006 | 0.006 |
| 245 | CYS | 273 | ALA | 0.252 | 0.246 | 0.006 | 0.006 |
| 60 | ILE | 64 | ILE | 0.540 | 0.535 | 0.005 | 0.005 |
| 191 | LEU | 194 | LEU | 0.004 | 0.000 | 0.004 | 0.004 |
| 269 | LEU | 272 | LEU | 0.077 | 0.074 | 0.004 | 0.004 |
| 223 | SER | 224 | THR | 0.344 | 0.347 | -0.003 | 0.003 |
| 285 | PRO | 288 | TYR | 0.002 | 0.000 | 0.002 | 0.002 |
| 265 | ALA | 269 | LEU | 0.178 | 0.176 | 0.001 | 0.001 |
| 259 | CYS | 260 | PRO | 0.129 | 0.129 | 0.001 | 0.001 |
| 24 | ASN | 284 | ASN | 0.158 | 0.158 | 0.000 | 0.000 |
RRCS change distribution
0.01
Mean ΔRRCS
1.41
Std Dev
0.01
Median
Magnitude classification
12
High (|Δ| ≥ 5.0)
80
Medium (2.0 ≤ |Δ| < 5.0)
660
Low (|Δ| < 2.0)
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| ≥ 1.97, 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