TRFR
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 | ASN347 | TYR348 | 18.386 | 0.000 | +18.386 | HIGH |
| 2 | ARG185 (5.32x32) | TYR192 (5.39x39) | 9.638 | 0.000 | +9.638 | HIGH |
| 3 | GLU122 (3.49x49) | ARG123 (3.50x50) | 0.000 | 8.263 | -8.263 | HIGH |
| 4 | TYR181 (45.52x52) | TYR188 (5.35x35) | 10.421 | 2.958 | +7.463 | HIGH |
| 5 | TYR181 (45.52x52) | ARG185 (5.32x32) | 7.302 | 0.000 | +7.302 | HIGH |
| 6 | GLU122 (3.49x49) | ARG141 (4.41x41) | 7.050 | 0.000 | +7.050 | HIGH |
| 7 | ILE183 (5.30x30) | TYR188 (5.35x35) | 8.397 | 1.882 | +6.516 | HIGH |
| 8 | TYR211 (5.58x58) | ALA269 (6.38x38) | 0.000 | 6.481 | -6.481 | HIGH |
| 9 | PHE119 (3.46x46) | LEU268 (6.37x37) | 0.000 | 6.188 | -6.188 | HIGH |
| 10 | TYR63 (2.42x42) | GLU122 (3.49x49) | 6.989 | 0.855 | +6.134 | HIGH |
| 11 | TRP279 (6.48x48) | ILE309 (7.42x41) | 1.159 | 7.194 | -6.035 | HIGH |
| 12 | ASN321 (7.54x54) | ARG328 (8.51x51) | 0.000 | 6.031 | -6.031 | HIGH |
| 13 | TYR156 (4.56x56) | PHE199 (5.46x46) | 0.900 | 6.772 | -5.872 | HIGH |
| 14 | ARG185 (5.32x32) | TYR188 (5.35x35) | 0.000 | 5.568 | -5.568 | HIGH |
| 15 | SER189 (5.36x36) | SER290 (6.59x59) | 7.336 | 1.854 | +5.482 | HIGH |
| 16 | LEU163 (4.63x63) | TYR188 (5.35x35) | 5.371 | 0.000 | +5.371 | HIGH |
| 17 | ASN321 (7.54x54) | PHE327 (8.50x50) | 9.151 | 3.988 | +5.162 | HIGH |
| 18 | LEU14 | TYR171 | 0.000 | 4.946 | -4.946 | MED |
| 19 | MET73 (2.52x52) | LEU104 (3.31x31) | 0.684 | 5.605 | -4.921 | MED |
| 20 | TYR106 (3.33x33) | TRP160 (4.60x60) | 15.867 | 20.653 | -4.786 | MED |
| 21 | LEU64 (2.43x43) | ASN321 (7.54x54) | 4.637 | 0.000 | +4.637 | MED |
| 22 | LEU14 | THR170 | 0.000 | 4.528 | -4.528 | MED |
| 23 | THR60 (2.39x39) | ARG123 (3.50x50) | 0.000 | 4.462 | -4.462 | MED |
| 24 | PHE139 (4.39x39) | LYS143 (4.43x43) | 0.000 | 4.434 | -4.434 | MED |
| 25 | ASN221 (5.68x68) | ARG261 (6.30x30) | 4.424 | 0.000 | +4.424 | MED |
| 26 | TRP300 (7.33x32) | PHE301 (7.34x33) | 4.410 | 0.000 | +4.410 | MED |
| 27 | VAL46 (1.53x53) | ASN321 (7.54x54) | 4.331 | 0.000 | +4.331 | MED |
| 28 | PHE275 (6.44x44) | ASN312 (7.45x45) | 0.354 | 4.616 | -4.263 | MED |
| 29 | SER360 | ASP361 | 4.758 | 0.560 | +4.198 | MED |
| 30 | ASP368 | ASP369 | 4.075 | 0.000 | +4.075 | MED |
| 31 | THR53 (1.60x60) | HIS55 (12.49x49) | 0.000 | 4.046 | -4.046 | MED |
| 32 | ASP165 | LYS182 | 2.955 | 6.916 | -3.961 | MED |
| 33 | THR60 (2.39x39) | GLU122 (3.49x49) | 0.000 | 3.957 | -3.957 | MED |
| 34 | ASN186 (5.33x33) | SER290 (6.59x59) | 3.928 | 0.000 | +3.928 | MED |
| 35 | ASP85 (2.64x63) | TRP91 (23.50x50) | 3.908 | 0.000 | +3.908 | MED |
| 36 | TRP91 (23.50x50) | TYR93 (23.52x52) | 7.254 | 3.414 | +3.840 | MED |
| 37 | LEU163 (4.63x63) | TYR181 (45.52x52) | 0.929 | 4.686 | -3.756 | MED |
| 38 | PRO222 (5.69x69) | ARG261 (6.30x30) | 3.698 | 0.000 | +3.698 | MED |
| 39 | LEU218 (5.65x65) | LYS262 (6.31x31) | 0.000 | 3.575 | -3.575 | MED |
| 40 | TYR156 (4.56x56) | ILE191 (5.38x38) | 4.056 | 0.495 | +3.561 | MED |
| 41 | VAL318 (7.51x51) | MET323 (7.56x56) | 3.557 | 0.000 | +3.557 | MED |
| 42 | ARG185 (5.32x32) | VAL286 (6.55x55) | 3.548 | 0.000 | +3.548 | MED |
| 43 | TYR156 (4.56x56) | MET194 (5.41x41) | 5.094 | 1.548 | +3.545 | MED |
| 44 | LEU136 (34.56x56) | ARG141 (4.41x41) | 10.024 | 6.507 | +3.517 | MED |
| 45 | TYR320 (7.53x53) | PHE327 (8.50x50) | 0.000 | 3.502 | -3.502 | MED |
| 46 | ILE223 (5.70x70) | LYS262 (6.31x31) | 0.000 | 3.483 | -3.483 | MED |
| 47 | TYR181 (45.52x52) | TYR192 (5.39x39) | 4.138 | 7.556 | -3.418 | MED |
| 48 | TYR354 | SER355 | 3.414 | 0.000 | +3.414 | MED |
| 49 | ALA77 (2.56x551) | GLN105 (3.32x32) | 4.594 | 1.220 | +3.374 | MED |
| 50 | ILE223 (5.70x70) | ARG261 (6.30x30) | 3.238 | 0.000 | +3.238 | MED |
| 51 | LEU218 (5.65x65) | ARG261 (6.30x30) | 3.209 | 0.000 | +3.209 | MED |
| 52 | TYR103 (3.30x30) | MET158 (4.58x58) | 1.736 | 4.887 | -3.151 | MED |
| 53 | ASN321 (7.54x54) | PHE331 (8.54x54) | 0.000 | 3.107 | -3.107 | MED |
| 54 | PRO295 | GLN297 | 0.034 | 3.134 | -3.099 | MED |
| 55 | GLU298 (7.31x30) | TRP300 (7.33x32) | 3.093 | 0.000 | +3.093 | MED |
| 56 | MET56 (12.50x50) | ASN61 (2.40x40) | 9.927 | 6.845 | +3.082 | MED |
| 57 | MET51 (1.58x58) | ARG57 (12.51x51) | 0.000 | 3.071 | -3.071 | MED |
| 58 | MET267 (6.36x36) | MET323 (7.56x56) | 1.495 | 4.533 | -3.038 | MED |
| 59 | ILE116 | PHE119 (3.46x46) | 0.000 | 2.993 | -2.993 | MED |
| 60 | GLN263 | MET323 (7.56x56) | 0.000 | 2.987 | -2.987 | MED |
| 61 | LEU159 | TRP160 (4.60x60) | 0.000 | 2.965 | -2.965 | MED |
| 62 | LEU14 | LYS172 | 13.609 | 10.697 | +2.912 | MED |
| 63 | TYR93 (23.52x52) | ILE101 | 0.000 | 2.867 | -2.867 | MED |
| 64 | TYR156 (4.56x56) | LEU159 | 0.044 | 2.826 | -2.782 | MED |
| 65 | TYR24 | ASN299 | 2.731 | 5.458 | -2.728 | MED |
| 66 | MET267 (6.36x36) | TYR320 (7.53x53) | 0.000 | 2.722 | -2.722 | MED |
| 67 | LYS144 | PHE148 | 2.688 | 0.000 | +2.688 | MED |
| 68 | ASN110 | ARG283 | 3.545 | 0.863 | +2.682 | MED |
| 69 | LYS182 | TYR188 (5.35x35) | 2.649 | 0.000 | +2.649 | MED |
| 70 | GLN105 (3.32x32) | TYR106 (3.33x33) | 0.000 | 2.617 | -2.617 | MED |
| 71 | GLY42 | PRO317 | 2.137 | 4.749 | -2.612 | MED |
| 72 | TYR192 (5.39x39) | VAL286 (6.55x55) | 6.488 | 3.903 | +2.585 | MED |
| 73 | TYR124 | LEU210 | 5.643 | 3.075 | +2.568 | MED |
| 74 | ASP195 | ARG283 | 2.350 | 4.883 | -2.534 | MED |
| 75 | LYS266 | MET323 (7.56x56) | 0.000 | 2.460 | -2.460 | MED |
| 76 | PRO203 | PHE275 (6.44x44) | 2.399 | 0.000 | +2.399 | MED |
| 77 | ARG328 (8.51x51) | ARG332 | 0.000 | 2.397 | -2.397 | MED |
| 78 | ARG17 | TYR171 | 0.000 | 2.379 | -2.379 | LOW |
| 79 | ASP71 | ASN316 | 5.498 | 3.122 | +2.377 | LOW |
| 80 | MET73 (2.52x52) | LEU107 | 0.163 | 2.536 | -2.373 | LOW |
| 81 | ASN167 | TYR181 (45.52x52) | 4.101 | 1.764 | +2.337 | LOW |
| 82 | SER290 (6.59x59) | PHE291 | 2.332 | 0.000 | +2.332 | LOW |
| 83 | ARG123 (3.50x50) | TYR211 (5.58x58) | 2.332 | 0.000 | +2.332 | LOW |
| 84 | ARG123 (3.50x50) | THR265 | 0.000 | 2.316 | -2.316 | LOW |
| 85 | ILE370 | THR371 | 2.268 | 0.000 | +2.268 | LOW |
| 86 | TRP160 (4.60x60) | TYR181 (45.52x52) | 0.948 | 3.205 | -2.257 | LOW |
| 87 | THR375 | TYR376 | 2.216 | 0.000 | +2.216 | LOW |
| 88 | ASN43 | ALA68 | 7.275 | 5.073 | +2.202 | LOW |
| 89 | HIS55 (12.49x49) | MET56 (12.50x50) | 0.000 | 2.189 | -2.189 | LOW |
| 90 | ASN82 | TYR310 | 4.510 | 2.322 | +2.188 | LOW |
| 91 | VAL49 | PHE327 (8.50x50) | 4.025 | 1.839 | +2.187 | LOW |
| 92 | TRP160 (4.60x60) | TYR192 (5.39x39) | 4.088 | 1.902 | +2.186 | LOW |
| 93 | ALA78 | GLN105 (3.32x32) | 4.251 | 2.074 | +2.177 | LOW |
| 94 | PHE119 (3.46x46) | TYR320 (7.53x53) | 2.170 | 0.000 | +2.170 | LOW |
| 95 | VAL356 | ILE357 | 2.862 | 0.699 | +2.163 | LOW |
| 96 | ILE109 | ARG283 | 3.190 | 1.061 | +2.129 | LOW |
| 97 | GLN15 | TYR171 | 0.887 | 2.988 | -2.100 | LOW |
| 98 | ILE116 | PHE275 (6.44x44) | 1.287 | 3.385 | -2.098 | LOW |
| 99 | PRO317 | LEU322 | 2.091 | 0.000 | +2.091 | LOW |
| 100 | ASN312 (7.45x45) | ASN316 | 2.080 | 0.000 | +2.080 | 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| ≥ 2.39 are shown (per-receptor significance threshold = max(mean(|Δ|) + σ, 0.2)).
| Segment | Range | Active-favoring residues | Count | Inactive-favoring residues | Count |
|---|---|---|---|---|---|
| TM1 | 46-53 | 46 (4.3) | 1 | 53 (-4.0), 51 (-3.1) | 2 |
| TM2 | 60-85 | 63 (6.1), 64 (4.6), 85 (3.9), 77 (3.4), 61 (3.1) | 5 | 73 (-4.9), 60 (-4.5) | 2 |
| TM3 | 103-123 | 105 (3.4) | 1 | 122 (-8.3), 123 (-8.3), 119 (-6.2), 104 (-4.9), 106 (-4.8), 103 (-3.2) | 6 |
| TM4 | 139-163 | 141 (7.1), 163 (5.4) | 2 | 156 (-5.9), 160 (-4.8), 139 (-4.4), 143 (-4.4), 158 (-3.2) | 5 |
| TM5 | 183-223 | 185 (9.6), 192 (9.6), 188 (7.5), 183 (6.5), 189 (5.5), 221 (4.4), 186 (3.9), 222 (3.7), 191 (3.6), 194 (3.5) | 10 | 211 (-6.5), 199 (-5.9), 218 (-3.6), 223 (-3.5) | 4 |
| TM6 | 261-290 | 290 (5.5), 261 (4.4), 286 (3.5) | 3 | 269 (-6.5), 268 (-6.2), 279 (-6.0), 275 (-4.3), 262 (-3.6), 267 (-3.0) | 6 |
| TM7 | 298-323 | 300 (4.4), 301 (4.4), 318 (3.6), 323 (3.6), 298 (3.1) | 5 | 309 (-6.0), 321 (-6.0), 312 (-4.3), 320 (-3.5) | 4 |
| Intracellular / Extracellular loops & H8 | |||||
| ICL1 | 55-57 | 56 (3.1) | 1 | 55 (-4.0), 57 (-3.1) | 2 |
| ICL2 | 136-136 | 136 (3.5) | 1 | - | 0 |
| ICL3 | - | - | 0 | - | 0 |
| ECL1 | 91-93 | 91 (3.9), 93 (3.8) | 2 | - | 0 |
| ECL2 | 165-182 | 181 (7.5) | 1 | 171 (-4.9), 170 (-4.5), 165 (-4.0), 182 (-4.0) | 4 |
| ECL3 | 295-297 | - | 0 | 295 (-3.1), 297 (-3.1) | 2 |
| H8 | 327-331 | 327 (5.2) | 1 | 328 (-6.0), 331 (-3.1) | 2 |
Interactive visualizations
ΔRRCS distribution
Active vs inactive comparison
Residue-wise changes
TM domain breakdown
Variants of interest
85 variants mapped to contact positions, sorted by |ΔRRCS| impact.
| Position | Protein change | DNA change | Allele freq | Het / Hom | ΔRRCS | AM score | Pathogenicity | Conservation | dbSNP |
|---|---|---|---|---|---|---|---|---|---|
| 348 | p.Tyr348His | c.1042T>C | 4.79e-06 | 7 / 0 | 18.39 | 0.265 | BENIGN | 0.57 | |
| 347 | p.Asn347Lys | c.1041C>A | 6.85e-07 | 1 / 0 | 18.39 | 0.149 | BENIGN | 0.41 | rs779373913 |
| 348 | p.Tyr348Asp | c.1042T>G | 4.79e-06 | 7 / 0 | 18.39 | - | nan | - | rs1305735496 |
| 348 | p.Tyr348Cys | c.1043A>G | 3.42e-06 | 5 / 0 | 18.39 | - | nan | - | |
| 185 | p.Arg185Gly | c.553A>G | 2.05e-06 | 3 / 0 | 9.64 | 0.929 | PATHOGENIC | 0.69 | |
| 185 | p.Arg185Trp | c.553A>T | 6.84e-07 | 1 / 0 | 9.64 | - | nan | - | |
| 185 | p.Arg185Lys | c.554G>A | 1.37e-06 | 2 / 0 | 9.64 | - | nan | - | rs777722173 |
| 185 | p.Arg185Ser | c.555G>C | 6.84e-07 | 1 / 0 | 9.64 | - | nan | - | |
| 123 | p.Arg123Gly | c.367A>G | 8.21e-06 | 12 / 0 | 8.26 | 0.996 | PATHOGENIC | 1.00 | |
| 188 | p.Tyr188Cys | c.563A>G | 6.84e-07 | 1 / 0 | 7.46 | 0.969 | PATHOGENIC | 0.79 | rs1351851219 |
| 141 | p.Arg141Lys | c.422G>A | 1.37e-06 | 2 / 0 | 7.05 | 0.714 | PATHOGENIC | 0.87 | |
| 141 | p.Arg141Ser | c.423A>C | 6.84e-07 | 1 / 0 | 7.05 | - | nan | - | |
| 183 | p.Ile183Asn | c.548T>A | 6.84e-07 | 1 / 0 | 6.52 | 0.713 | PATHOGENIC | 0.53 | rs1163112416 |
| 211 | p.Tyr211Cys | c.632A>G | 1.37e-06 | 2 / 0 | 6.48 | 0.959 | PATHOGENIC | 0.98 | rs753608641 |
| 269 | p.Ala269Thr | c.805G>A | 6.85e-07 | 1 / 0 | 6.48 | 0.397 | AMBIGUOUS | 0.55 | rs1811961519 |
| 269 | p.Ala269Val | c.806C>T | 6.85e-07 | 1 / 0 | 6.48 | - | nan | - | rs2129941740 |
| 309 | p.Ile309Val | c.925A>G | 6.84e-07 | 1 / 0 | 6.04 | 0.119 | BENIGN | 0.58 | rs1166237248 |
| 309 | p.Ile309Asn | c.926T>A | 6.84e-07 | 1 / 0 | 6.04 | - | nan | - | |
| 309 | p.Ile309Met | c.927T>G | 9.58e-06 | 14 / 0 | 6.04 | - | nan | - | rs755236670 |
| 328 | p.Arg328Cys | c.982C>T | 5.48e-06 | 8 / 0 | 6.03 | 0.914 | PATHOGENIC | 0.93 | rs745344271 |
| 321 | p.Asn321His | c.961A>C | 6.84e-07 | 1 / 0 | 6.03 | 0.495 | AMBIGUOUS | 0.77 | rs1811965612 |
| 321 | p.Asn321Ser | c.962A>G | 1.37e-06 | 2 / 0 | 6.03 | - | nan | - | |
| 328 | p.Arg328His | c.983G>A | 3.29e-05 | 48 / 0 | 6.03 | - | nan | - | rs769413252 |
| 199 | p.Phe199Leu | c.597T>G | 2.05e-06 | 3 / 0 | 5.87 | 0.997 | PATHOGENIC | 0.91 | rs1231037824 |
| 327 | p.Phe327Leu | c.979T>C | 6.84e-07 | 1 / 0 | 5.16 | 1.000 | PATHOGENIC | 0.96 | rs1200189208 |
| 14 | p.Leu14Pro | c.41T>C | 6.84e-07 | 1 / 0 | 4.95 | 0.083 | BENIGN | 0.62 | rs770577046 |
| 104 | p.Leu104Pro | c.311T>C | 6.84e-07 | 1 / 0 | 4.92 | 0.987 | PATHOGENIC | 0.67 | |
| 73 | p.Met73Leu | c.217A>C | 1.31e-04 | 190 / 0 | 4.92 | 0.158 | BENIGN | 0.59 | rs1811457976 |
| 73 | p.Met73Thr | c.218T>C | 2.74e-06 | 2 / 1 | 4.92 | - | nan | - | |
| 73 | p.Met73Ile | c.219G>A | 2.05e-06 | 3 / 0 | 4.92 | - | nan | - | rs761093674 |
| 106 | p.Tyr106His | c.316T>C | 3.42e-06 | 5 / 0 | 4.79 | 0.983 | PATHOGENIC | 0.60 | rs1806679667 |
| 160 | p.Trp160Ser | c.479G>C | 2.05e-06 | 3 / 0 | 4.79 | 0.960 | PATHOGENIC | 0.68 | |
| 170 | p.Thr170Ile | c.509C>T | 6.84e-07 | 1 / 0 | 4.53 | 0.077 | BENIGN | 0.28 | |
| 60 | p.Thr60Pro | c.178A>C | 6.84e-07 | 1 / 0 | 4.46 | 0.956 | PATHOGENIC | 0.99 | |
| 60 | p.Thr60Ile | c.179C>T | 1.37e-06 | 2 / 0 | 4.46 | - | nan | - | |
| 60 | p.Thr60Arg | c.179C>G | 6.84e-07 | 1 / 0 | 4.46 | - | nan | - | |
| 143 | p.Lys143Glu | c.427A>G | 6.84e-07 | 1 / 0 | 4.43 | 0.722 | PATHOGENIC | 0.67 | |
| 139 | p.Phe139Ile | c.415T>A | 6.84e-07 | 1 / 0 | 4.43 | 0.123 | BENIGN | 0.47 | rs1811463196 |
| 143 | p.Lys143Gln | c.427A>C | 1.23e-05 | 18 / 0 | 4.43 | - | nan | - | rs765710756 |
| 300 | p.Trp300Arg | c.898T>A | 6.16e-06 | 9 / 0 | 4.41 | 0.912 | PATHOGENIC | 0.57 | rs1389665014 |
| 301 | p.Phe301Val | c.901T>G | 6.84e-07 | 1 / 0 | 4.41 | 0.422 | AMBIGUOUS | 0.62 | rs754143691 |
| 300 | p.Trp300Ser | c.899G>C | 1.37e-06 | 2 / 0 | 4.41 | - | nan | - | |
| 300 | p.Trp300Cys | c.900G>T | 4.79e-06 | 7 / 0 | 4.41 | - | nan | - | |
| 312 | p.Asn312Ser | c.935A>G | 6.84e-07 | 1 / 0 | 4.26 | 0.816 | PATHOGENIC | 0.82 | |
| 361 | p.Asp361Gly | c.1082A>G | 2.74e-06 | 4 / 0 | 4.20 | 0.128 | BENIGN | 0.60 | rs1811969603 |
| 360 | p.Ser360Pro | c.1078T>C | 6.85e-07 | 1 / 0 | 4.20 | 0.115 | BENIGN | 0.59 | rs768273826 |
| 369 | p.Asp369Asn | c.1105G>A | 7.53e-06 | 11 / 0 | 4.08 | 0.104 | BENIGN | 0.75 | rs773072164 |
| 369 | p.Asp369Tyr | c.1105G>T | 6.85e-07 | 1 / 0 | 4.08 | - | nan | - | |
| 369 | p.Asp369Val | c.1106A>T | 6.85e-07 | 1 / 0 | 4.08 | - | nan | - | |
| 55 | p.His55Tyr | c.163C>T | 6.84e-07 | 1 / 0 | 4.05 | 0.289 | BENIGN | 0.44 | |
| 53 | p.Thr53Ser | c.158C>G | 1.37e-06 | 2 / 0 | 4.05 | 0.211 | BENIGN | 0.52 | |
| 165 | p.Asp165Asn | c.493G>A | 3.42e-06 | 5 / 0 | 3.96 | 0.340 | AMBIGUOUS | 0.54 | rs779945451 |
| 182 | p.Lys182Arg | c.545A>G | 6.84e-07 | 1 / 0 | 3.96 | 0.076 | BENIGN | 0.53 | |
| 186 | p.Asn186Lys | c.558T>G | 1.64e-05 | 24 / 0 | 3.93 | 0.120 | BENIGN | 0.40 | rs747217985 |
| 186 | p.Asn186Lys | c.558T>A | 1.37e-06 | 2 / 0 | 3.93 | - | nan | - | |
| 91 | p.Trp91Cys | c.273G>T | 6.84e-07 | 1 / 0 | 3.91 | 0.999 | PATHOGENIC | 0.85 | |
| 85 | p.Asp85Glu | c.255C>A | 6.84e-07 | 1 / 0 | 3.91 | 0.143 | BENIGN | 0.40 | rs1811459246 |
| 191 | p.Ile191Val | c.571A>G | 6.84e-07 | 1 / 0 | 3.56 | 0.094 | BENIGN | 0.56 | |
| 323 | p.Met323Val | c.967A>G | 6.84e-07 | 1 / 0 | 3.56 | 0.925 | PATHOGENIC | 0.88 | |
| 318 | p.Val318Met | c.952G>A | 6.84e-07 | 1 / 0 | 3.56 | 0.339 | BENIGN | 0.73 | rs1369849189 |
| 286 | p.Val286Met | c.856G>A | 6.84e-07 | 1 / 0 | 3.55 | 0.946 | PATHOGENIC | 0.63 | rs1268692700 |
| 194 | p.Met194Thr | c.581T>C | 1.09e-05 | 16 / 0 | 3.55 | 0.143 | BENIGN | 0.41 | rs961397728 |
| 194 | p.Met194Ile | c.582G>A | 6.84e-07 | 1 / 0 | 3.55 | - | nan | - | |
| 320 | p.Tyr320Ser | c.959A>C | 6.84e-07 | 1 / 0 | 3.50 | 0.987 | PATHOGENIC | 0.99 | |
| 320 | p.Tyr320Cys | c.959A>G | 3.42e-06 | 5 / 0 | 3.50 | - | nan | - | rs1811965555 |
| 223 | p.Ile223Val | c.667A>G | 1.09e-05 | 16 / 0 | 3.48 | 0.085 | BENIGN | 0.49 | rs758302656 |
| 223 | p.Ile223Met | c.669T>G | 6.84e-07 | 1 / 0 | 3.48 | - | nan | - | rs777865512 |
| 105 | p.Gln105Lys | c.313C>A | 6.57e-06 | 1 / 0 | 3.37 | 0.977 | PATHOGENIC | 0.58 | rs1811460739 |
| 77 | p.Ala77Gly | c.230C>G | 6.84e-07 | 1 / 0 | 3.37 | 0.577 | PATHOGENIC | 0.57 | |
| 77 | p.Ala77Val | c.230C>T | 6.84e-07 | 1 / 0 | 3.37 | - | nan | - | rs1415204106 |
| 103 | p.Tyr103His | c.307T>C | 2.74e-06 | 4 / 0 | 3.15 | 0.955 | PATHOGENIC | 0.72 | rs1171639399 |
| 331 | p.Phe331Val | c.991T>G | 6.59e-06 | 1 / 0 | 3.11 | 0.953 | PATHOGENIC | 0.93 | rs1811966707 |
| 295 | p.Pro295Ser | c.883C>T | 4.79e-06 | 7 / 0 | 3.10 | 0.194 | BENIGN | 0.51 | rs756257265 |
| 295 | p.Pro295Thr | c.883C>A | 6.84e-07 | 1 / 0 | 3.10 | - | nan | - | |
| 295 | p.Pro295Arg | c.884C>G | 4.18e-05 | 61 / 0 | 3.10 | - | nan | - | rs780131397 |
| 298 | p.Glu298Lys | c.892G>A | 6.84e-07 | 1 / 0 | 3.09 | 0.237 | BENIGN | 0.51 | rs1392795394 |
| 61 | p.Asn61Asp | c.181A>G | 1.34e-04 | 194 / 1 | 3.08 | 0.981 | PATHOGENIC | 0.89 | rs145365134 |
| 56 | p.Met56Val | c.166A>G | 6.57e-06 | 1 / 0 | 3.08 | 0.964 | PATHOGENIC | 0.89 | rs1214964830 |
| 56 | p.Met56Ile | c.168G>A | 1.37e-06 | 2 / 0 | 3.08 | - | nan | - | rs1811456262 |
| 57 | p.Arg57Lys | c.170G>A | 6.84e-07 | 1 / 0 | 3.07 | 0.160 | BENIGN | 0.52 | rs1323544142 |
| 51 | p.Met51Val | c.151A>G | 1.37e-06 | 2 / 0 | 3.07 | 0.070 | BENIGN | 0.46 | |
| 51 | p.Met51Leu | c.151A>C | 1.37e-06 | 2 / 0 | 3.07 | - | nan | - | rs908519851 |
| 51 | p.Met51Arg | c.152T>G | 1.37e-06 | 2 / 0 | 3.07 | - | nan | - | rs144587571 |
| 51 | p.Met51Lys | c.152T>A | 6.84e-07 | 1 / 0 | 3.07 | - | nan | - | |
| 57 | p.Arg57Met | c.170G>T | 6.84e-07 | 1 / 0 | 3.07 | - | nan | - |
Complete RRCS results
Top 1000 contact pairs by |ΔRRCS|. Significance threshold: |ΔRRCS| ≥ 2.39, computed as max(mean(|Δ|) + σ, 0.2). Highlighted rows indicate significant changes.
| Res1 | AA1 | Res2 | AA2 | Active RRCS | Inactive RRCS | ΔRRCS | |ΔRRCS| |
|---|---|---|---|---|---|---|---|
| 347 | ASN | 348 | TYR | 18.386 | 0.000 | 18.386 | 18.386 |
| 185 | ARG | 192 | TYR | 9.638 | 0.000 | 9.638 | 9.638 |
| 122 | GLU | 123 | ARG | 0.000 | 8.263 | -8.263 | 8.263 |
| 181 | TYR | 188 | TYR | 10.421 | 2.958 | 7.463 | 7.463 |
| 181 | TYR | 185 | ARG | 7.302 | 0.000 | 7.302 | 7.302 |
| 122 | GLU | 141 | ARG | 7.050 | 0.000 | 7.050 | 7.050 |
| 183 | ILE | 188 | TYR | 8.397 | 1.882 | 6.516 | 6.516 |
| 211 | TYR | 269 | ALA | 0.000 | 6.481 | -6.481 | 6.481 |
| 119 | PHE | 268 | LEU | 0.000 | 6.188 | -6.188 | 6.188 |
| 63 | TYR | 122 | GLU | 6.989 | 0.855 | 6.134 | 6.134 |
| 279 | TRP | 309 | ILE | 1.159 | 7.194 | -6.035 | 6.035 |
| 321 | ASN | 328 | ARG | 0.000 | 6.031 | -6.031 | 6.031 |
| 156 | TYR | 199 | PHE | 0.900 | 6.772 | -5.872 | 5.872 |
| 185 | ARG | 188 | TYR | 0.000 | 5.568 | -5.568 | 5.568 |
| 189 | SER | 290 | SER | 7.336 | 1.854 | 5.482 | 5.482 |
| 163 | LEU | 188 | TYR | 5.371 | 0.000 | 5.371 | 5.371 |
| 321 | ASN | 327 | PHE | 9.151 | 3.988 | 5.162 | 5.162 |
| 14 | LEU | 171 | TYR | 0.000 | 4.946 | -4.946 | 4.946 |
| 73 | MET | 104 | LEU | 0.684 | 5.605 | -4.921 | 4.921 |
| 106 | TYR | 160 | TRP | 15.867 | 20.653 | -4.786 | 4.786 |
| 64 | LEU | 321 | ASN | 4.637 | 0.000 | 4.637 | 4.637 |
| 14 | LEU | 170 | THR | 0.000 | 4.528 | -4.528 | 4.528 |
| 60 | THR | 123 | ARG | 0.000 | 4.462 | -4.462 | 4.462 |
| 139 | PHE | 143 | LYS | 0.000 | 4.434 | -4.434 | 4.434 |
| 221 | ASN | 261 | ARG | 4.424 | 0.000 | 4.424 | 4.424 |
| 300 | TRP | 301 | PHE | 4.410 | 0.000 | 4.410 | 4.410 |
| 46 | VAL | 321 | ASN | 4.331 | 0.000 | 4.331 | 4.331 |
| 275 | PHE | 312 | ASN | 0.354 | 4.616 | -4.263 | 4.263 |
| 360 | SER | 361 | ASP | 4.758 | 0.560 | 4.198 | 4.198 |
| 368 | ASP | 369 | ASP | 4.075 | 0.000 | 4.075 | 4.075 |
| 53 | THR | 55 | HIS | 0.000 | 4.046 | -4.046 | 4.046 |
| 165 | ASP | 182 | LYS | 2.955 | 6.916 | -3.961 | 3.961 |
| 60 | THR | 122 | GLU | 0.000 | 3.957 | -3.957 | 3.957 |
| 186 | ASN | 290 | SER | 3.928 | 0.000 | 3.928 | 3.928 |
| 85 | ASP | 91 | TRP | 3.908 | 0.000 | 3.908 | 3.908 |
| 91 | TRP | 93 | TYR | 7.254 | 3.414 | 3.840 | 3.840 |
| 163 | LEU | 181 | TYR | 0.929 | 4.686 | -3.756 | 3.756 |
| 222 | PRO | 261 | ARG | 3.698 | 0.000 | 3.698 | 3.698 |
| 218 | LEU | 262 | LYS | 0.000 | 3.575 | -3.575 | 3.575 |
| 156 | TYR | 191 | ILE | 4.056 | 0.495 | 3.561 | 3.561 |
| 318 | VAL | 323 | MET | 3.557 | 0.000 | 3.557 | 3.557 |
| 185 | ARG | 286 | VAL | 3.548 | 0.000 | 3.548 | 3.548 |
| 156 | TYR | 194 | MET | 5.094 | 1.548 | 3.545 | 3.545 |
| 136 | LEU | 141 | ARG | 10.024 | 6.507 | 3.517 | 3.517 |
| 320 | TYR | 327 | PHE | 0.000 | 3.502 | -3.502 | 3.502 |
| 223 | ILE | 262 | LYS | 0.000 | 3.483 | -3.483 | 3.483 |
| 181 | TYR | 192 | TYR | 4.138 | 7.556 | -3.418 | 3.418 |
| 354 | TYR | 355 | SER | 3.414 | 0.000 | 3.414 | 3.414 |
| 77 | ALA | 105 | GLN | 4.594 | 1.220 | 3.374 | 3.374 |
| 223 | ILE | 261 | ARG | 3.238 | 0.000 | 3.238 | 3.238 |
| 218 | LEU | 261 | ARG | 3.209 | 0.000 | 3.209 | 3.209 |
| 103 | TYR | 158 | MET | 1.736 | 4.887 | -3.151 | 3.151 |
| 321 | ASN | 331 | PHE | 0.000 | 3.107 | -3.107 | 3.107 |
| 295 | PRO | 297 | GLN | 0.034 | 3.134 | -3.099 | 3.099 |
| 298 | GLU | 300 | TRP | 3.093 | 0.000 | 3.093 | 3.093 |
| 56 | MET | 61 | ASN | 9.927 | 6.845 | 3.082 | 3.082 |
| 51 | MET | 57 | ARG | 0.000 | 3.071 | -3.071 | 3.071 |
| 267 | MET | 323 | MET | 1.495 | 4.533 | -3.038 | 3.038 |
| 116 | ILE | 119 | PHE | 0.000 | 2.993 | -2.993 | 2.993 |
| 263 | GLN | 323 | MET | 0.000 | 2.987 | -2.987 | 2.987 |
| 159 | LEU | 160 | TRP | 0.000 | 2.965 | -2.965 | 2.965 |
| 14 | LEU | 172 | LYS | 13.609 | 10.697 | 2.912 | 2.912 |
| 93 | TYR | 101 | ILE | 0.000 | 2.867 | -2.867 | 2.867 |
| 156 | TYR | 159 | LEU | 0.044 | 2.826 | -2.782 | 2.782 |
| 24 | TYR | 299 | ASN | 2.731 | 5.458 | -2.728 | 2.728 |
| 267 | MET | 320 | TYR | 0.000 | 2.722 | -2.722 | 2.722 |
| 144 | LYS | 148 | PHE | 2.688 | 0.000 | 2.688 | 2.688 |
| 110 | ASN | 283 | ARG | 3.545 | 0.863 | 2.682 | 2.682 |
| 182 | LYS | 188 | TYR | 2.649 | 0.000 | 2.649 | 2.649 |
| 105 | GLN | 106 | TYR | 0.000 | 2.617 | -2.617 | 2.617 |
| 42 | GLY | 317 | PRO | 2.137 | 4.749 | -2.612 | 2.612 |
| 192 | TYR | 286 | VAL | 6.488 | 3.903 | 2.585 | 2.585 |
| 124 | TYR | 210 | LEU | 5.643 | 3.075 | 2.568 | 2.568 |
| 195 | ASP | 283 | ARG | 2.350 | 4.883 | -2.534 | 2.534 |
| 266 | LYS | 323 | MET | 0.000 | 2.460 | -2.460 | 2.460 |
| 203 | PRO | 275 | PHE | 2.399 | 0.000 | 2.399 | 2.399 |
| 328 | ARG | 332 | ARG | 0.000 | 2.397 | -2.397 | 2.397 |
| 17 | ARG | 171 | TYR | 0.000 | 2.379 | -2.379 | 2.379 |
| 71 | ASP | 316 | ASN | 5.498 | 3.122 | 2.377 | 2.377 |
| 73 | MET | 107 | LEU | 0.163 | 2.536 | -2.373 | 2.373 |
| 167 | ASN | 181 | TYR | 4.101 | 1.764 | 2.337 | 2.337 |
| 290 | SER | 291 | PHE | 2.332 | 0.000 | 2.332 | 2.332 |
| 123 | ARG | 211 | TYR | 2.332 | 0.000 | 2.332 | 2.332 |
| 123 | ARG | 265 | THR | 0.000 | 2.316 | -2.316 | 2.316 |
| 370 | ILE | 371 | THR | 2.268 | 0.000 | 2.268 | 2.268 |
| 160 | TRP | 181 | TYR | 0.948 | 3.205 | -2.257 | 2.257 |
| 375 | THR | 376 | TYR | 2.216 | 0.000 | 2.216 | 2.216 |
| 43 | ASN | 68 | ALA | 7.275 | 5.073 | 2.202 | 2.202 |
| 55 | HIS | 56 | MET | 0.000 | 2.189 | -2.189 | 2.189 |
| 82 | ASN | 310 | TYR | 4.510 | 2.322 | 2.188 | 2.188 |
| 49 | VAL | 327 | PHE | 4.025 | 1.839 | 2.187 | 2.187 |
| 160 | TRP | 192 | TYR | 4.088 | 1.902 | 2.186 | 2.186 |
| 78 | ALA | 105 | GLN | 4.251 | 2.074 | 2.177 | 2.177 |
| 119 | PHE | 320 | TYR | 2.170 | 0.000 | 2.170 | 2.170 |
| 356 | VAL | 357 | ILE | 2.862 | 0.699 | 2.163 | 2.163 |
| 109 | ILE | 283 | ARG | 3.190 | 1.061 | 2.129 | 2.129 |
| 15 | GLN | 171 | TYR | 0.887 | 2.988 | -2.100 | 2.100 |
| 116 | ILE | 275 | PHE | 1.287 | 3.385 | -2.098 | 2.098 |
| 317 | PRO | 322 | LEU | 2.091 | 0.000 | 2.091 | 2.091 |
| 312 | ASN | 316 | ASN | 2.080 | 0.000 | 2.080 | 2.080 |
| 110 | ASN | 195 | ASP | 2.082 | 4.116 | -2.034 | 2.034 |
| 208 | THR | 272 | VAL | 2.010 | 0.000 | 2.010 | 2.010 |
| 369 | ASP | 370 | ILE | 0.257 | 2.264 | -2.007 | 2.007 |
| 15 | GLN | 172 | LYS | 0.000 | 1.974 | -1.974 | 1.974 |
| 160 | TRP | 191 | ILE | 1.969 | 0.000 | 1.969 | 1.969 |
| 311 | LEU | 315 | ILE | 1.979 | 0.016 | 1.963 | 1.963 |
| 62 | CYS | 146 | ILE | 0.720 | 2.679 | -1.959 | 1.959 |
| 278 | LEU | 308 | CYS | 5.234 | 7.174 | -1.940 | 1.940 |
| 138 | THR | 141 | ARG | 0.738 | 2.664 | -1.927 | 1.927 |
| 81 | PRO | 93 | TYR | 3.131 | 4.984 | -1.853 | 1.853 |
| 280 | MET | 284 | THR | 2.501 | 0.656 | 1.845 | 1.845 |
| 116 | ILE | 320 | TYR | 1.821 | 0.000 | 1.821 | 1.821 |
| 148 | PHE | 152 | PHE | 1.869 | 0.053 | 1.815 | 1.815 |
| 58 | THR | 139 | PHE | 2.159 | 0.365 | 1.794 | 1.794 |
| 113 | SER | 275 | PHE | 1.277 | 3.067 | -1.790 | 1.790 |
| 13 | GLN | 170 | THR | 1.725 | 0.000 | 1.725 | 1.725 |
| 44 | ILE | 72 | LEU | 0.201 | 1.899 | -1.697 | 1.697 |
| 107 | LEU | 154 | SER | 1.218 | 2.914 | -1.697 | 1.697 |
| 119 | PHE | 120 | THR | 0.000 | 1.696 | -1.696 | 1.696 |
| 56 | MET | 327 | PHE | 0.417 | 2.082 | -1.665 | 1.665 |
| 211 | TYR | 265 | THR | 0.000 | 1.658 | -1.658 | 1.658 |
| 206 | LEU | 210 | LEU | 0.218 | 1.870 | -1.651 | 1.651 |
| 17 | ARG | 89 | GLY | 5.589 | 3.948 | 1.641 | 1.641 |
| 271 | VAL | 316 | ASN | 0.000 | 1.638 | -1.638 | 1.638 |
| 192 | TYR | 287 | VAL | 1.632 | 0.000 | 1.632 | 1.632 |
| 185 | ARG | 292 | LEU | 0.000 | 1.601 | -1.601 | 1.601 |
| 219 | PHE | 265 | THR | 1.601 | 0.000 | 1.601 | 1.601 |
| 141 | ARG | 145 | ILE | 1.594 | 0.000 | 1.594 | 1.594 |
| 17 | ARG | 88 | TYR | 0.449 | 2.037 | -1.588 | 1.588 |
| 103 | TYR | 161 | PHE | 4.836 | 6.409 | -1.574 | 1.574 |
| 183 | ILE | 187 | TYR | 1.292 | 2.866 | -1.573 | 1.573 |
| 361 | ASP | 362 | HIS | 1.563 | 0.000 | 1.563 | 1.563 |
| 257 | THR | 261 | ARG | 1.554 | 0.000 | 1.554 | 1.554 |
| 152 | PHE | 199 | PHE | 0.000 | 1.536 | -1.536 | 1.536 |
| 126 | ALA | 261 | ARG | 0.000 | 1.531 | -1.531 | 1.531 |
| 124 | TYR | 129 | HIS | 1.162 | 2.691 | -1.529 | 1.529 |
| 67 | LEU | 115 | SER | 2.246 | 0.724 | 1.521 | 1.521 |
| 199 | PHE | 283 | ARG | 1.798 | 0.277 | 1.521 | 1.521 |
| 160 | TRP | 188 | TYR | 1.515 | 0.000 | 1.515 | 1.515 |
| 242 | ASN | 243 | THR | 0.000 | 1.511 | -1.511 | 1.511 |
| 143 | LYS | 147 | ILE | 1.508 | 0.000 | 1.508 | 1.508 |
| 109 | ILE | 279 | TRP | 5.001 | 6.491 | -1.491 | 1.491 |
| 62 | CYS | 139 | PHE | 0.808 | 2.291 | -1.484 | 1.484 |
| 275 | PHE | 279 | TRP | 4.650 | 6.118 | -1.468 | 1.468 |
| 117 | THR | 203 | PRO | 3.571 | 2.105 | 1.466 | 1.466 |
| 73 | MET | 108 | GLY | 0.319 | 1.773 | -1.454 | 1.454 |
| 66 | SER | 146 | ILE | 3.598 | 2.149 | 1.449 | 1.449 |
| 25 | GLN | 86 | SER | 4.700 | 3.252 | 1.448 | 1.448 |
| 82 | ASN | 306 | ARG | 5.708 | 4.265 | 1.443 | 1.443 |
| 128 | CYS | 217 | ILE | 0.372 | 1.809 | -1.437 | 1.437 |
| 160 | TRP | 164 | LEU | 1.681 | 0.250 | 1.431 | 1.431 |
| 189 | SER | 291 | PHE | 1.425 | 0.000 | 1.425 | 1.425 |
| 73 | MET | 150 | TRP | 2.435 | 1.023 | 1.411 | 1.411 |
| 211 | TYR | 272 | VAL | 1.160 | 2.563 | -1.404 | 1.404 |
| 70 | ALA | 112 | SER | 1.740 | 3.142 | -1.402 | 1.402 |
| 127 | ILE | 265 | THR | 0.000 | 1.400 | -1.400 | 1.400 |
| 123 | ARG | 268 | LEU | 3.292 | 1.896 | 1.396 | 1.396 |
| 75 | LEU | 80 | LEU | 1.064 | 2.446 | -1.382 | 1.382 |
| 64 | LEU | 320 | TYR | 1.339 | 2.720 | -1.381 | 1.381 |
| 127 | ILE | 261 | ARG | 0.000 | 1.375 | -1.375 | 1.375 |
| 43 | ASN | 72 | LEU | 0.795 | 2.166 | -1.371 | 1.371 |
| 69 | VAL | 150 | TRP | 0.461 | 1.830 | -1.369 | 1.369 |
| 355 | SER | 356 | VAL | 1.366 | 0.000 | 1.366 | 1.366 |
| 186 | ASN | 292 | LEU | 1.362 | 0.000 | 1.362 | 1.362 |
| 200 | TYR | 279 | TRP | 2.395 | 1.037 | 1.358 | 1.358 |
| 31 | LEU | 35 | ILE | 1.334 | 0.000 | 1.334 | 1.334 |
| 362 | HIS | 363 | PHE | 0.000 | 1.321 | -1.321 | 1.321 |
| 221 | ASN | 262 | LYS | 0.000 | 1.319 | -1.319 | 1.319 |
| 167 | ASN | 178 | SER | 8.502 | 9.818 | -1.316 | 1.316 |
| 331 | PHE | 335 | CYS | 3.214 | 1.901 | 1.314 | 1.314 |
| 164 | LEU | 181 | TYR | 0.000 | 1.305 | -1.305 | 1.305 |
| 267 | MET | 319 | ILE | 0.120 | 1.421 | -1.302 | 1.302 |
| 29 | ILE | 86 | SER | 1.500 | 0.216 | 1.284 | 1.284 |
| 28 | THR | 86 | SER | 0.424 | 1.701 | -1.278 | 1.278 |
| 45 | MET | 334 | LEU | 0.000 | 1.277 | -1.277 | 1.277 |
| 60 | THR | 119 | PHE | 1.269 | 0.000 | 1.269 | 1.269 |
| 71 | ASP | 112 | SER | 2.838 | 1.572 | 1.266 | 1.266 |
| 76 | VAL | 81 | PRO | 0.669 | 1.929 | -1.261 | 1.261 |
| 46 | VAL | 320 | TYR | 0.000 | 1.259 | -1.259 | 1.259 |
| 56 | MET | 326 | LYS | 0.000 | 1.257 | -1.257 | 1.257 |
| 135 | PHE | 141 | ARG | 0.000 | 1.244 | -1.244 | 1.244 |
| 235 | LYS | 236 | ASN | 0.186 | 1.412 | -1.227 | 1.227 |
| 391 | SER | 392 | GLU | 1.226 | 0.000 | 1.226 | 1.226 |
| 279 | TRP | 283 | ARG | 1.978 | 0.755 | 1.224 | 1.224 |
| 122 | GLU | 137 | CYS | 1.775 | 2.989 | -1.214 | 1.214 |
| 62 | CYS | 142 | ALA | 1.320 | 0.112 | 1.209 | 1.209 |
| 111 | ALA | 153 | THR | 1.306 | 2.507 | -1.201 | 1.201 |
| 20 | VAL | 25 | GLN | 1.823 | 0.622 | 1.201 | 1.201 |
| 110 | ASN | 199 | PHE | 12.219 | 13.417 | -1.198 | 1.198 |
| 101 | ILE | 105 | GLN | 1.262 | 0.085 | 1.177 | 1.177 |
| 45 | MET | 331 | PHE | 2.562 | 3.724 | -1.162 | 1.162 |
| 36 | CYS | 75 | LEU | 2.524 | 1.373 | 1.151 | 1.151 |
| 36 | CYS | 310 | TYR | 1.196 | 0.072 | 1.124 | 1.124 |
| 119 | PHE | 272 | VAL | 0.000 | 1.116 | -1.116 | 1.116 |
| 46 | VAL | 327 | PHE | 2.149 | 3.264 | -1.115 | 1.115 |
| 164 | LEU | 180 | GLY | 2.315 | 3.420 | -1.105 | 1.105 |
| 123 | ARG | 126 | ALA | 0.000 | 1.099 | -1.099 | 1.099 |
| 296 | PHE | 298 | GLU | 4.449 | 3.355 | 1.094 | 1.094 |
| 27 | VAL | 300 | TRP | 0.000 | 1.093 | -1.093 | 1.093 |
| 74 | VAL | 108 | GLY | 2.628 | 1.540 | 1.088 | 1.088 |
| 106 | TYR | 192 | TYR | 1.022 | 2.092 | -1.071 | 1.071 |
| 137 | CYS | 141 | ARG | 1.065 | 0.000 | 1.065 | 1.065 |
| 43 | ASN | 313 | SER | 1.470 | 2.535 | -1.064 | 1.064 |
| 204 | MET | 275 | PHE | 0.966 | 2.010 | -1.044 | 1.044 |
| 204 | MET | 276 | ALA | 0.810 | 1.835 | -1.025 | 1.025 |
| 102 | THR | 164 | LEU | 2.212 | 3.236 | -1.024 | 1.024 |
| 113 | SER | 203 | PRO | 0.781 | 1.803 | -1.022 | 1.022 |
| 119 | PHE | 211 | TYR | 0.000 | 1.020 | -1.020 | 1.020 |
| 116 | ILE | 272 | VAL | 0.000 | 1.012 | -1.012 | 1.012 |
| 202 | VAL | 206 | LEU | 1.009 | 0.000 | 1.009 | 1.009 |
| 258 | VAL | 262 | LYS | 0.276 | 1.284 | -1.007 | 1.007 |
| 163 | LEU | 191 | ILE | 1.029 | 2.036 | -1.007 | 1.007 |
| 185 | ARG | 295 | PRO | 0.401 | 1.406 | -1.005 | 1.005 |
| 157 | CYS | 160 | TRP | 0.000 | 1.003 | -1.003 | 1.003 |
| 200 | TYR | 280 | MET | 5.086 | 4.096 | 0.990 | 0.990 |
| 50 | VAL | 56 | MET | 2.451 | 1.464 | 0.987 | 0.987 |
| 270 | VAL | 323 | MET | 0.000 | 0.985 | -0.985 | 0.985 |
| 169 | SER | 171 | TYR | 0.484 | 1.459 | -0.976 | 0.976 |
| 91 | TRP | 177 | ILE | 4.002 | 4.975 | -0.973 | 0.973 |
| 303 | LEU | 307 | ILE | 2.204 | 1.232 | 0.972 | 0.972 |
| 62 | CYS | 143 | LYS | 0.970 | 0.000 | 0.970 | 0.970 |
| 57 | ARG | 139 | PHE | 1.999 | 2.968 | -0.969 | 0.969 |
| 267 | MET | 324 | SER | 0.000 | 0.957 | -0.957 | 0.957 |
| 214 | ILE | 265 | THR | 0.000 | 0.950 | -0.950 | 0.950 |
| 32 | VAL | 83 | ILE | 0.538 | 1.487 | -0.949 | 0.949 |
| 158 | MET | 161 | PHE | 0.412 | 1.361 | -0.949 | 0.949 |
| 50 | VAL | 57 | ARG | 0.000 | 0.946 | -0.946 | 0.946 |
| 162 | PHE | 182 | LYS | 0.941 | 0.000 | 0.941 | 0.941 |
| 82 | ASN | 86 | SER | 0.000 | 0.938 | -0.938 | 0.938 |
| 359 | GLU | 360 | SER | 0.938 | 0.000 | 0.938 | 0.938 |
| 211 | TYR | 271 | VAL | 0.935 | 0.000 | 0.935 | 0.935 |
| 32 | VAL | 310 | TYR | 0.150 | 1.085 | -0.934 | 0.934 |
| 2 | GLU | 3 | ASN | 0.000 | 0.932 | -0.932 | 0.932 |
| 27 | VAL | 31 | LEU | 0.000 | 0.931 | -0.931 | 0.931 |
| 28 | THR | 82 | ASN | 0.000 | 0.927 | -0.927 | 0.927 |
| 85 | ASP | 90 | SER | 1.842 | 0.917 | 0.925 | 0.925 |
| 24 | TYR | 28 | THR | 2.707 | 3.630 | -0.923 | 0.923 |
| 315 | ILE | 319 | ILE | 1.769 | 0.848 | 0.922 | 0.922 |
| 226 | ASP | 227 | PRO | 1.411 | 0.499 | 0.913 | 0.913 |
| 52 | ARG | 334 | LEU | 0.907 | 0.000 | 0.907 | 0.907 |
| 198 | VAL | 199 | PHE | 1.901 | 2.806 | -0.904 | 0.904 |
| 282 | TYR | 283 | ARG | 0.961 | 0.065 | 0.897 | 0.897 |
| 125 | ILE | 136 | LEU | 0.000 | 0.894 | -0.894 | 0.894 |
| 214 | ILE | 268 | LEU | 0.891 | 0.000 | 0.891 | 0.891 |
| 16 | PRO | 173 | ASP | 0.937 | 0.052 | 0.885 | 0.885 |
| 324 | SER | 327 | PHE | 0.746 | 1.626 | -0.879 | 0.879 |
| 320 | TYR | 321 | ASN | 0.876 | 0.000 | 0.876 | 0.876 |
| 74 | VAL | 313 | SER | 2.060 | 1.186 | 0.874 | 0.874 |
| 91 | TRP | 101 | ILE | 1.159 | 2.026 | -0.866 | 0.866 |
| 316 | ASN | 320 | TYR | 1.755 | 2.618 | -0.862 | 0.862 |
| 67 | LEU | 116 | ILE | 1.231 | 0.373 | 0.858 | 0.858 |
| 300 | TRP | 303 | LEU | 0.000 | 0.850 | -0.850 | 0.850 |
| 70 | ALA | 108 | GLY | 2.848 | 3.695 | -0.847 | 0.847 |
| 127 | ILE | 214 | ILE | 0.989 | 0.143 | 0.846 | 0.846 |
| 171 | TYR | 176 | VAL | 1.422 | 2.265 | -0.843 | 0.843 |
| 90 | SER | 177 | ILE | 4.541 | 5.374 | -0.833 | 0.833 |
| 160 | TRP | 163 | LEU | 0.000 | 0.825 | -0.825 | 0.825 |
| 103 | TYR | 154 | SER | 3.538 | 4.360 | -0.822 | 0.822 |
| 123 | ARG | 264 | VAL | 0.095 | 0.913 | -0.818 | 0.818 |
| 396 | SER | 397 | GLN | 0.236 | 1.053 | -0.817 | 0.817 |
| 66 | SER | 150 | TRP | 4.514 | 3.701 | 0.813 | 0.813 |
| 113 | SER | 199 | PHE | 4.646 | 3.834 | 0.812 | 0.812 |
| 196 | PHE | 287 | VAL | 1.587 | 2.399 | -0.812 | 0.812 |
| 274 | LEU | 312 | ASN | 0.278 | 1.087 | -0.809 | 0.809 |
| 281 | PRO | 305 | CYS | 2.903 | 2.095 | 0.808 | 0.808 |
| 247 | VAL | 251 | ASN | 1.031 | 0.235 | 0.796 | 0.796 |
| 60 | THR | 64 | LEU | 0.795 | 0.000 | 0.795 | 0.795 |
| 211 | TYR | 268 | LEU | 4.378 | 3.594 | 0.783 | 0.783 |
| 17 | ARG | 176 | VAL | 2.103 | 1.332 | 0.772 | 0.772 |
| 166 | LEU | 179 | CYS | 1.041 | 0.271 | 0.770 | 0.770 |
| 271 | VAL | 320 | TYR | 1.939 | 1.174 | 0.766 | 0.766 |
| 114 | CYS | 149 | VAL | 1.155 | 1.900 | -0.745 | 0.745 |
| 32 | VAL | 82 | ASN | 0.036 | 0.769 | -0.734 | 0.734 |
| 185 | ARG | 290 | SER | 0.855 | 1.581 | -0.727 | 0.727 |
| 274 | LEU | 315 | ILE | 0.107 | 0.833 | -0.726 | 0.726 |
| 159 | LEU | 163 | LEU | 0.226 | 0.949 | -0.723 | 0.723 |
| 304 | PHE | 308 | CYS | 1.782 | 2.505 | -0.723 | 0.723 |
| 196 | PHE | 284 | THR | 0.707 | 0.000 | 0.707 | 0.707 |
| 278 | LEU | 312 | ASN | 3.347 | 2.641 | 0.706 | 0.706 |
| 81 | PRO | 101 | ILE | 0.630 | 1.325 | -0.695 | 0.695 |
| 81 | PRO | 91 | TRP | 0.692 | 0.000 | 0.692 | 0.692 |
| 70 | ALA | 111 | ALA | 1.385 | 0.696 | 0.690 | 0.690 |
| 306 | ARG | 310 | TYR | 2.472 | 1.783 | 0.689 | 0.689 |
| 121 | ILE | 210 | LEU | 0.986 | 1.675 | -0.689 | 0.689 |
| 237 | ASP | 242 | ASN | 0.684 | 0.000 | 0.684 | 0.684 |
| 107 | LEU | 153 | THR | 2.182 | 2.864 | -0.682 | 0.682 |
| 112 | SER | 316 | ASN | 0.679 | 0.000 | 0.679 | 0.679 |
| 90 | SER | 176 | VAL | 2.467 | 1.793 | 0.674 | 0.674 |
| 13 | GLN | 171 | TYR | 0.674 | 0.000 | 0.674 | 0.674 |
| 71 | ASP | 313 | SER | 11.490 | 12.160 | -0.670 | 0.670 |
| 94 | GLY | 166 | LEU | 2.064 | 1.398 | 0.667 | 0.667 |
| 59 | PRO | 137 | CYS | 1.881 | 2.546 | -0.665 | 0.665 |
| 242 | ASN | 245 | LEU | 0.665 | 0.000 | 0.665 | 0.665 |
| 95 | TYR | 165 | ASP | 2.223 | 1.559 | 0.664 | 0.664 |
| 122 | GLU | 145 | ILE | 0.654 | 0.000 | 0.654 | 0.654 |
| 215 | ALA | 265 | THR | 0.649 | 0.000 | 0.649 | 0.649 |
| 64 | LEU | 268 | LEU | 0.000 | 0.644 | -0.644 | 0.644 |
| 309 | ILE | 310 | TYR | 0.139 | 0.784 | -0.644 | 0.644 |
| 110 | ASN | 157 | CYS | 0.308 | 0.946 | -0.638 | 0.638 |
| 75 | LEU | 310 | TYR | 2.329 | 1.693 | 0.636 | 0.636 |
| 107 | LEU | 157 | CYS | 2.884 | 2.251 | 0.634 | 0.634 |
| 60 | THR | 268 | LEU | 0.000 | 0.633 | -0.633 | 0.633 |
| 233 | THR | 234 | TRP | 0.326 | 0.958 | -0.632 | 0.632 |
| 109 | ILE | 282 | TYR | 0.629 | 0.000 | 0.629 | 0.629 |
| 77 | ALA | 101 | ILE | 1.897 | 2.525 | -0.628 | 0.628 |
| 357 | ILE | 358 | LYS | 0.658 | 0.030 | 0.628 | 0.628 |
| 279 | TRP | 282 | TYR | 0.056 | 0.683 | -0.627 | 0.627 |
| 84 | THR | 93 | TYR | 4.945 | 5.572 | -0.627 | 0.627 |
| 270 | VAL | 319 | ILE | 0.000 | 0.622 | -0.622 | 0.622 |
| 250 | SER | 251 | ASN | 0.000 | 0.620 | -0.620 | 0.620 |
| 28 | THR | 303 | LEU | 3.283 | 3.904 | -0.620 | 0.620 |
| 128 | CYS | 214 | ILE | 0.962 | 0.345 | 0.616 | 0.616 |
| 318 | VAL | 322 | LEU | 0.292 | 0.906 | -0.614 | 0.614 |
| 289 | ASN | 296 | PHE | 7.145 | 7.756 | -0.611 | 0.611 |
| 79 | GLY | 310 | TYR | 3.907 | 4.517 | -0.610 | 0.610 |
| 163 | LEU | 183 | ILE | 0.253 | 0.853 | -0.600 | 0.600 |
| 195 | ASP | 199 | PHE | 2.871 | 2.272 | 0.599 | 0.599 |
| 63 | TYR | 118 | ALA | 1.545 | 2.144 | -0.598 | 0.598 |
| 32 | VAL | 307 | ILE | 0.000 | 0.598 | -0.598 | 0.598 |
| 109 | ILE | 309 | ILE | 0.592 | 0.000 | 0.592 | 0.592 |
| 322 | LEU | 327 | PHE | 0.591 | 0.000 | 0.591 | 0.591 |
| 165 | ASP | 181 | TYR | 0.632 | 0.049 | 0.583 | 0.583 |
| 35 | ILE | 314 | ALA | 1.143 | 1.722 | -0.579 | 0.579 |
| 120 | THR | 272 | VAL | 0.000 | 0.577 | -0.577 | 0.577 |
| 123 | ARG | 214 | ILE | 1.250 | 0.676 | 0.574 | 0.574 |
| 49 | VAL | 330 | ALA | 0.667 | 1.236 | -0.569 | 0.569 |
| 349 | SER | 350 | VAL | 0.000 | 0.569 | -0.569 | 0.569 |
| 35 | ILE | 307 | ILE | 0.559 | 1.115 | -0.556 | 0.556 |
| 352 | LEU | 353 | ASN | 0.000 | 0.554 | -0.554 | 0.554 |
| 67 | LEU | 316 | ASN | 1.570 | 1.016 | 0.553 | 0.553 |
| 267 | MET | 268 | LEU | 0.000 | 0.553 | -0.553 | 0.553 |
| 319 | ILE | 323 | MET | 0.000 | 0.549 | -0.549 | 0.549 |
| 129 | HIS | 132 | LYS | 0.570 | 1.117 | -0.547 | 0.547 |
| 223 | ILE | 259 | SER | 0.000 | 0.546 | -0.546 | 0.546 |
| 270 | VAL | 274 | LEU | 1.212 | 0.668 | 0.544 | 0.544 |
| 120 | THR | 211 | TYR | 3.786 | 4.330 | -0.543 | 0.543 |
| 47 | VAL | 65 | VAL | 0.091 | 0.633 | -0.542 | 0.542 |
| 110 | ASN | 156 | TYR | 0.819 | 1.358 | -0.539 | 0.539 |
| 87 | ILE | 88 | TYR | 0.816 | 1.355 | -0.539 | 0.539 |
| 98 | CYS | 179 | CYS | 6.958 | 7.495 | -0.537 | 0.537 |
| 246 | ASN | 249 | THR | 0.537 | 0.000 | 0.537 | 0.537 |
| 91 | TRP | 179 | CYS | 3.732 | 4.267 | -0.535 | 0.535 |
| 185 | ARG | 289 | ASN | 2.993 | 2.458 | 0.534 | 0.534 |
| 40 | ILE | 72 | LEU | 2.180 | 2.711 | -0.531 | 0.531 |
| 67 | LEU | 71 | ASP | 2.276 | 1.745 | 0.531 | 0.531 |
| 91 | TRP | 166 | LEU | 1.417 | 0.887 | 0.531 | 0.531 |
| 98 | CYS | 164 | LEU | 0.302 | 0.829 | -0.526 | 0.526 |
| 207 | ALA | 272 | VAL | 1.200 | 0.675 | 0.525 | 0.525 |
| 90 | SER | 175 | ILE | 0.676 | 0.151 | 0.525 | 0.525 |
| 113 | SER | 279 | TRP | 0.525 | 0.000 | 0.525 | 0.525 |
| 132 | LYS | 136 | LEU | 0.000 | 0.524 | -0.524 | 0.524 |
| 378 | SER | 379 | ALA | 0.520 | 0.000 | 0.520 | 0.520 |
| 61 | ASN | 64 | LEU | 0.350 | 0.869 | -0.519 | 0.519 |
| 325 | GLN | 328 | ARG | 0.518 | 0.000 | 0.518 | 0.518 |
| 218 | LEU | 265 | THR | 0.516 | 0.000 | 0.516 | 0.516 |
| 91 | TRP | 97 | GLY | 2.654 | 2.138 | 0.516 | 0.516 |
| 85 | ASP | 306 | ARG | 0.000 | 0.509 | -0.509 | 0.509 |
| 74 | VAL | 310 | TYR | 0.509 | 0.000 | 0.509 | 0.509 |
| 188 | TYR | 192 | TYR | 1.883 | 2.387 | -0.503 | 0.503 |
| 66 | SER | 115 | SER | 2.841 | 2.339 | 0.502 | 0.502 |
| 169 | SER | 176 | VAL | 7.775 | 7.273 | 0.501 | 0.501 |
| 319 | ILE | 320 | TYR | 0.569 | 0.068 | 0.500 | 0.500 |
| 72 | LEU | 76 | VAL | 0.500 | 0.000 | 0.500 | 0.500 |
| 196 | PHE | 283 | ARG | 2.431 | 2.929 | -0.499 | 0.499 |
| 184 | SER | 187 | TYR | 0.954 | 1.450 | -0.496 | 0.496 |
| 196 | PHE | 200 | TYR | 3.221 | 3.716 | -0.495 | 0.495 |
| 69 | VAL | 73 | MET | 0.492 | 0.000 | 0.492 | 0.492 |
| 102 | THR | 179 | CYS | 1.078 | 0.587 | 0.491 | 0.491 |
| 49 | VAL | 56 | MET | 0.330 | 0.819 | -0.489 | 0.489 |
| 110 | ASN | 153 | THR | 1.431 | 1.920 | -0.489 | 0.489 |
| 126 | ALA | 133 | ALA | 1.835 | 1.347 | 0.488 | 0.488 |
| 196 | PHE | 201 | VAL | 5.373 | 5.861 | -0.487 | 0.487 |
| 78 | ALA | 310 | TYR | 5.711 | 5.227 | 0.483 | 0.483 |
| 370 | ILE | 372 | VAL | 0.000 | 0.481 | -0.481 | 0.481 |
| 50 | VAL | 61 | ASN | 1.611 | 2.090 | -0.479 | 0.479 |
| 153 | THR | 199 | PHE | 0.000 | 0.478 | -0.478 | 0.478 |
| 16 | PRO | 171 | TYR | 0.000 | 0.477 | -0.477 | 0.477 |
| 106 | TYR | 181 | TYR | 0.628 | 1.104 | -0.476 | 0.476 |
| 189 | SER | 190 | PRO | 0.854 | 1.327 | -0.473 | 0.473 |
| 125 | ILE | 137 | CYS | 0.324 | 0.797 | -0.473 | 0.473 |
| 114 | CYS | 199 | PHE | 1.763 | 1.291 | 0.472 | 0.472 |
| 36 | CYS | 79 | GLY | 0.810 | 1.281 | -0.471 | 0.471 |
| 281 | PRO | 304 | PHE | 1.766 | 1.297 | 0.469 | 0.469 |
| 237 | ASP | 239 | THR | 0.513 | 0.046 | 0.467 | 0.467 |
| 81 | PRO | 105 | GLN | 0.464 | 0.000 | 0.464 | 0.464 |
| 107 | LEU | 150 | TRP | 1.429 | 0.966 | 0.464 | 0.464 |
| 111 | ALA | 149 | VAL | 0.000 | 0.463 | -0.463 | 0.463 |
| 74 | VAL | 105 | GLN | 0.000 | 0.460 | -0.460 | 0.460 |
| 126 | ALA | 137 | CYS | 0.000 | 0.460 | -0.460 | 0.460 |
| 134 | GLN | 372 | VAL | 0.000 | 0.454 | -0.454 | 0.454 |
| 280 | MET | 281 | PRO | 1.521 | 1.070 | 0.451 | 0.451 |
| 45 | MET | 335 | CYS | 0.000 | 0.451 | -0.451 | 0.451 |
| 363 | PHE | 364 | SER | 0.000 | 0.451 | -0.451 | 0.451 |
| 98 | CYS | 166 | LEU | 1.204 | 0.754 | 0.450 | 0.450 |
| 116 | ILE | 316 | ASN | 0.450 | 0.000 | 0.450 | 0.450 |
| 49 | VAL | 331 | PHE | 1.901 | 1.456 | 0.444 | 0.444 |
| 40 | ILE | 76 | VAL | 0.970 | 0.528 | 0.442 | 0.442 |
| 120 | THR | 206 | LEU | 0.439 | 0.000 | 0.439 | 0.439 |
| 316 | ASN | 319 | ILE | 0.000 | 0.438 | -0.438 | 0.438 |
| 198 | VAL | 203 | PRO | 2.113 | 2.551 | -0.438 | 0.438 |
| 167 | ASN | 180 | GLY | 1.266 | 1.703 | -0.438 | 0.438 |
| 289 | ASN | 295 | PRO | 3.489 | 3.052 | 0.437 | 0.437 |
| 46 | VAL | 317 | PRO | 0.763 | 1.200 | -0.437 | 0.437 |
| 128 | CYS | 213 | PHE | 0.435 | 0.000 | 0.435 | 0.435 |
| 121 | ILE | 206 | LEU | 0.089 | 0.522 | -0.433 | 0.433 |
| 335 | CYS | 336 | ASN | 0.082 | 0.513 | -0.431 | 0.431 |
| 218 | LEU | 264 | VAL | 0.431 | 0.000 | 0.431 | 0.431 |
| 40 | ILE | 80 | LEU | 0.000 | 0.431 | -0.431 | 0.431 |
| 124 | TYR | 214 | ILE | 1.447 | 1.875 | -0.428 | 0.428 |
| 285 | LEU | 289 | ASN | 2.437 | 2.862 | -0.425 | 0.425 |
| 365 | THR | 366 | GLU | 0.000 | 0.416 | -0.416 | 0.416 |
| 45 | MET | 327 | PHE | 0.427 | 0.011 | 0.416 | 0.416 |
| 209 | VAL | 213 | PHE | 1.395 | 1.809 | -0.414 | 0.414 |
| 24 | TYR | 303 | LEU | 3.137 | 2.724 | 0.413 | 0.413 |
| 395 | PHE | 396 | SER | 0.000 | 0.411 | -0.411 | 0.411 |
| 39 | GLY | 314 | ALA | 2.183 | 2.591 | -0.409 | 0.409 |
| 163 | LEU | 182 | LYS | 3.480 | 3.072 | 0.409 | 0.409 |
| 120 | THR | 210 | LEU | 1.155 | 1.559 | -0.404 | 0.404 |
| 60 | THR | 264 | VAL | 0.000 | 0.403 | -0.403 | 0.403 |
| 125 | ILE | 141 | ARG | 0.402 | 0.000 | 0.402 | 0.402 |
| 95 | TYR | 164 | LEU | 0.586 | 0.186 | 0.400 | 0.400 |
| 67 | LEU | 271 | VAL | 0.000 | 0.399 | -0.399 | 0.399 |
| 63 | TYR | 142 | ALA | 4.076 | 3.678 | 0.398 | 0.398 |
| 127 | ILE | 128 | CYS | 0.000 | 0.396 | -0.396 | 0.396 |
| 84 | THR | 85 | ASP | 0.394 | 0.000 | 0.394 | 0.394 |
| 103 | TYR | 107 | LEU | 1.684 | 2.076 | -0.391 | 0.391 |
| 88 | TYR | 92 | VAL | 2.263 | 1.876 | 0.387 | 0.387 |
| 36 | CYS | 80 | LEU | 0.000 | 0.387 | -0.387 | 0.387 |
| 285 | LEU | 296 | PHE | 0.890 | 1.277 | -0.387 | 0.387 |
| 203 | PRO | 204 | MET | 0.000 | 0.385 | -0.385 | 0.385 |
| 200 | TYR | 276 | ALA | 3.571 | 3.186 | 0.385 | 0.385 |
| 59 | PRO | 122 | GLU | 0.000 | 0.382 | -0.382 | 0.382 |
| 239 | THR | 240 | HIS | 0.000 | 0.376 | -0.376 | 0.376 |
| 312 | ASN | 313 | SER | 0.000 | 0.368 | -0.368 | 0.368 |
| 185 | ARG | 293 | SER | 0.000 | 0.365 | -0.365 | 0.365 |
| 25 | GLN | 87 | ILE | 0.272 | 0.637 | -0.365 | 0.365 |
| 156 | TYR | 195 | ASP | 6.744 | 7.108 | -0.364 | 0.364 |
| 95 | TYR | 99 | LEU | 3.678 | 4.040 | -0.362 | 0.362 |
| 131 | ILE | 135 | PHE | 0.361 | 0.000 | 0.361 | 0.361 |
| 102 | THR | 106 | TYR | 1.766 | 1.407 | 0.360 | 0.360 |
| 254 | PHE | 258 | VAL | 1.818 | 1.467 | 0.351 | 0.351 |
| 226 | ASP | 228 | LYS | 0.000 | 0.348 | -0.348 | 0.348 |
| 31 | LEU | 307 | ILE | 1.317 | 0.970 | 0.347 | 0.347 |
| 24 | TYR | 300 | TRP | 2.544 | 2.888 | -0.345 | 0.345 |
| 215 | ALA | 219 | PHE | 0.174 | 0.518 | -0.345 | 0.345 |
| 46 | VAL | 64 | LEU | 0.300 | 0.640 | -0.341 | 0.341 |
| 220 | LEU | 221 | ASN | 0.010 | 0.350 | -0.341 | 0.341 |
| 263 | GLN | 325 | GLN | 0.000 | 0.338 | -0.338 | 0.338 |
| 35 | ILE | 310 | TYR | 2.249 | 2.578 | -0.328 | 0.328 |
| 278 | LEU | 311 | LEU | 0.871 | 1.199 | -0.328 | 0.328 |
| 63 | TYR | 145 | ILE | 3.671 | 3.997 | -0.326 | 0.326 |
| 153 | THR | 157 | CYS | 0.326 | 0.000 | 0.326 | 0.326 |
| 152 | PHE | 153 | THR | 0.000 | 0.324 | -0.324 | 0.324 |
| 50 | VAL | 65 | VAL | 1.728 | 2.046 | -0.318 | 0.318 |
| 182 | LYS | 183 | ILE | 0.057 | 0.371 | -0.314 | 0.314 |
| 301 | PHE | 304 | PHE | 0.722 | 0.409 | 0.313 | 0.313 |
| 193 | LEU | 291 | PHE | 0.954 | 1.264 | -0.311 | 0.311 |
| 168 | ILE | 170 | THR | 0.309 | 0.000 | 0.309 | 0.309 |
| 130 | PRO | 261 | ARG | 0.000 | 0.309 | -0.309 | 0.309 |
| 111 | ALA | 150 | TRP | 2.153 | 1.845 | 0.308 | 0.308 |
| 293 | SER | 294 | SER | 0.306 | 0.000 | 0.306 | 0.306 |
| 95 | TYR | 166 | LEU | 3.593 | 3.898 | -0.305 | 0.305 |
| 315 | ILE | 316 | ASN | 0.000 | 0.305 | -0.305 | 0.305 |
| 59 | PRO | 139 | PHE | 1.463 | 1.159 | 0.305 | 0.305 |
| 156 | TYR | 157 | CYS | 0.083 | 0.386 | -0.303 | 0.303 |
| 274 | LEU | 278 | LEU | 0.250 | 0.552 | -0.302 | 0.302 |
| 216 | ARG | 220 | LEU | 1.354 | 1.055 | 0.299 | 0.299 |
| 24 | TYR | 306 | ARG | 0.000 | 0.297 | -0.297 | 0.297 |
| 301 | PHE | 305 | CYS | 1.637 | 1.932 | -0.295 | 0.295 |
| 236 | ASN | 237 | ASP | 0.295 | 0.000 | 0.295 | 0.295 |
| 74 | VAL | 109 | ILE | 1.872 | 1.579 | 0.292 | 0.292 |
| 45 | MET | 48 | LEU | 0.000 | 0.292 | -0.292 | 0.292 |
| 63 | TYR | 119 | PHE | 2.445 | 2.737 | -0.292 | 0.292 |
| 134 | GLN | 135 | PHE | 0.000 | 0.291 | -0.291 | 0.291 |
| 64 | LEU | 267 | MET | 0.000 | 0.291 | -0.291 | 0.291 |
| 279 | TRP | 312 | ASN | 5.589 | 5.877 | -0.288 | 0.288 |
| 67 | LEU | 119 | PHE | 0.000 | 0.287 | -0.287 | 0.287 |
| 99 | LEU | 164 | LEU | 1.295 | 1.582 | -0.286 | 0.286 |
| 119 | PHE | 271 | VAL | 0.000 | 0.284 | -0.284 | 0.284 |
| 58 | THR | 60 | THR | 0.622 | 0.338 | 0.284 | 0.284 |
| 64 | LEU | 119 | PHE | 0.280 | 0.000 | 0.280 | 0.280 |
| 80 | LEU | 83 | ILE | 0.568 | 0.290 | 0.278 | 0.278 |
| 162 | PHE | 183 | ILE | 0.000 | 0.278 | -0.278 | 0.278 |
| 285 | LEU | 305 | CYS | 0.927 | 0.650 | 0.277 | 0.277 |
| 333 | LYS | 337 | CYS | 0.000 | 0.275 | -0.275 | 0.275 |
| 164 | LEU | 182 | LYS | 1.162 | 0.889 | 0.272 | 0.272 |
| 56 | MET | 330 | ALA | 0.520 | 0.248 | 0.272 | 0.272 |
| 298 | GLU | 301 | PHE | 0.050 | 0.320 | -0.270 | 0.270 |
| 273 | ILE | 277 | LEU | 1.076 | 0.809 | 0.268 | 0.268 |
| 274 | LEU | 319 | ILE | 0.929 | 1.195 | -0.266 | 0.266 |
| 113 | SER | 283 | ARG | 0.265 | 0.000 | 0.265 | 0.265 |
| 60 | THR | 61 | ASN | 0.345 | 0.083 | 0.263 | 0.263 |
| 138 | THR | 140 | SER | 0.369 | 0.107 | 0.262 | 0.262 |
| 296 | PHE | 301 | PHE | 2.950 | 3.210 | -0.260 | 0.260 |
| 74 | VAL | 309 | ILE | 0.749 | 0.490 | 0.259 | 0.259 |
| 120 | THR | 207 | ALA | 1.328 | 1.069 | 0.259 | 0.259 |
| 47 | VAL | 69 | VAL | 0.027 | 0.286 | -0.259 | 0.259 |
| 237 | ASP | 238 | SER | 0.000 | 0.257 | -0.257 | 0.257 |
| 16 | PRO | 172 | LYS | 0.000 | 0.256 | -0.256 | 0.256 |
| 175 | ILE | 177 | ILE | 0.256 | 0.000 | 0.256 | 0.256 |
| 257 | THR | 258 | VAL | 0.000 | 0.255 | -0.255 | 0.255 |
| 322 | LEU | 328 | ARG | 3.471 | 3.216 | 0.255 | 0.255 |
| 200 | TYR | 275 | PHE | 0.810 | 0.555 | 0.254 | 0.254 |
| 166 | LEU | 178 | SER | 2.549 | 2.295 | 0.254 | 0.254 |
| 82 | ASN | 85 | ASP | 0.000 | 0.252 | -0.252 | 0.252 |
| 73 | MET | 78 | ALA | 0.494 | 0.242 | 0.252 | 0.252 |
| 13 | GLN | 172 | LYS | 0.609 | 0.859 | -0.250 | 0.250 |
| 71 | ASP | 312 | ASN | 0.000 | 0.248 | -0.248 | 0.248 |
| 324 | SER | 326 | LYS | 0.635 | 0.387 | 0.248 | 0.248 |
| 282 | TYR | 309 | ILE | 4.833 | 4.587 | 0.247 | 0.247 |
| 43 | ASN | 71 | ASP | 2.742 | 2.498 | 0.245 | 0.245 |
| 204 | MET | 272 | VAL | 0.019 | 0.259 | -0.240 | 0.240 |
| 17 | ARG | 90 | SER | 0.000 | 0.240 | -0.240 | 0.240 |
| 167 | ASN | 177 | ILE | 1.824 | 1.591 | 0.233 | 0.233 |
| 346 | ALA | 347 | ASN | 0.421 | 0.189 | 0.232 | 0.232 |
| 49 | VAL | 53 | THR | 0.232 | 0.000 | 0.232 | 0.232 |
| 115 | SER | 149 | VAL | 0.204 | 0.435 | -0.231 | 0.231 |
| 197 | GLY | 202 | VAL | 3.645 | 3.876 | -0.231 | 0.231 |
| 70 | ALA | 150 | TRP | 2.720 | 2.491 | 0.229 | 0.229 |
| 199 | PHE | 275 | PHE | 0.494 | 0.265 | 0.229 | 0.229 |
| 127 | ILE | 262 | LYS | 0.000 | 0.228 | -0.228 | 0.228 |
| 189 | SER | 193 | LEU | 0.000 | 0.227 | -0.227 | 0.227 |
| 46 | VAL | 68 | ALA | 0.750 | 0.977 | -0.226 | 0.226 |
| 53 | THR | 330 | ALA | 0.798 | 0.572 | 0.226 | 0.226 |
| 92 | VAL | 93 | TYR | 1.503 | 1.279 | 0.224 | 0.224 |
| 149 | VAL | 153 | THR | 0.305 | 0.082 | 0.223 | 0.223 |
| 201 | VAL | 205 | ILE | 1.182 | 0.960 | 0.222 | 0.222 |
| 159 | LEU | 191 | ILE | 0.971 | 1.193 | -0.221 | 0.221 |
| 165 | ASP | 180 | GLY | 6.278 | 6.057 | 0.221 | 0.221 |
| 80 | LEU | 93 | TYR | 0.398 | 0.179 | 0.219 | 0.219 |
| 200 | TYR | 204 | MET | 0.681 | 0.897 | -0.216 | 0.216 |
| 125 | ILE | 133 | ALA | 1.834 | 2.049 | -0.216 | 0.216 |
| 380 | THR | 382 | VAL | 0.000 | 0.207 | -0.207 | 0.207 |
| 397 | GLN | 398 | SER | 0.000 | 0.206 | -0.206 | 0.206 |
| 223 | ILE | 224 | PRO | 0.843 | 1.047 | -0.204 | 0.204 |
| 316 | ASN | 321 | ASN | 0.203 | 0.000 | 0.203 | 0.203 |
| 163 | LEU | 180 | GLY | 0.140 | 0.343 | -0.203 | 0.203 |
| 45 | MET | 49 | VAL | 0.200 | 0.000 | 0.200 | 0.200 |
| 117 | THR | 121 | ILE | 0.272 | 0.472 | -0.199 | 0.199 |
| 124 | TYR | 128 | CYS | 3.168 | 3.367 | -0.199 | 0.199 |
| 67 | LEU | 112 | SER | 3.053 | 3.250 | -0.197 | 0.197 |
| 297 | GLN | 302 | LEU | 1.430 | 1.624 | -0.195 | 0.195 |
| 28 | THR | 32 | VAL | 0.156 | 0.351 | -0.195 | 0.195 |
| 33 | LEU | 83 | ILE | 1.628 | 1.822 | -0.194 | 0.194 |
| 278 | LEU | 309 | ILE | 0.250 | 0.443 | -0.193 | 0.193 |
| 292 | LEU | 296 | PHE | 0.034 | 0.227 | -0.193 | 0.193 |
| 319 | ILE | 324 | SER | 0.000 | 0.192 | -0.192 | 0.192 |
| 340 | LYS | 341 | PRO | 0.535 | 0.726 | -0.191 | 0.191 |
| 112 | SER | 116 | ILE | 0.190 | 0.000 | 0.190 | 0.190 |
| 109 | ILE | 110 | ASN | 0.937 | 0.747 | 0.190 | 0.190 |
| 29 | ILE | 87 | ILE | 1.004 | 1.193 | -0.189 | 0.189 |
| 117 | THR | 206 | LEU | 0.647 | 0.835 | -0.188 | 0.188 |
| 124 | TYR | 213 | PHE | 1.386 | 1.198 | 0.188 | 0.188 |
| 217 | ILE | 221 | ASN | 0.750 | 0.563 | 0.187 | 0.187 |
| 214 | ILE | 218 | LEU | 0.799 | 0.985 | -0.187 | 0.187 |
| 389 | LEU | 390 | ALA | 0.000 | 0.186 | -0.186 | 0.186 |
| 76 | VAL | 80 | LEU | 0.442 | 0.256 | 0.186 | 0.186 |
| 27 | VAL | 303 | LEU | 0.000 | 0.186 | -0.186 | 0.186 |
| 197 | GLY | 203 | PRO | 0.000 | 0.184 | -0.184 | 0.184 |
| 63 | TYR | 146 | ILE | 3.091 | 2.910 | 0.181 | 0.181 |
| 119 | PHE | 123 | ARG | 0.181 | 0.000 | 0.181 | 0.181 |
| 75 | LEU | 314 | ALA | 0.241 | 0.063 | 0.178 | 0.178 |
| 67 | LEU | 320 | TYR | 1.229 | 1.054 | 0.175 | 0.175 |
| 329 | ALA | 332 | ARG | 0.184 | 0.010 | 0.175 | 0.175 |
| 48 | LEU | 334 | LEU | 0.531 | 0.706 | -0.174 | 0.174 |
| 32 | VAL | 36 | CYS | 0.450 | 0.624 | -0.174 | 0.174 |
| 206 | LEU | 211 | TYR | 0.174 | 0.000 | 0.174 | 0.174 |
| 39 | GLY | 75 | LEU | 2.384 | 2.210 | 0.174 | 0.174 |
| 165 | ASP | 178 | SER | 0.351 | 0.522 | -0.171 | 0.171 |
| 322 | LEU | 323 | MET | 0.000 | 0.169 | -0.169 | 0.169 |
| 43 | ASN | 75 | LEU | 0.602 | 0.433 | 0.169 | 0.169 |
| 287 | VAL | 291 | PHE | 0.716 | 0.884 | -0.169 | 0.169 |
| 205 | ILE | 209 | VAL | 0.252 | 0.084 | 0.168 | 0.168 |
| 285 | LEU | 301 | PHE | 2.433 | 2.265 | 0.167 | 0.167 |
| 43 | ASN | 317 | PRO | 4.682 | 4.849 | -0.167 | 0.167 |
| 74 | VAL | 79 | GLY | 1.153 | 1.320 | -0.167 | 0.167 |
| 194 | MET | 195 | ASP | 0.166 | 0.000 | 0.166 | 0.166 |
| 274 | LEU | 279 | TRP | 0.004 | 0.165 | -0.161 | 0.161 |
| 84 | THR | 92 | VAL | 0.764 | 0.604 | 0.160 | 0.160 |
| 183 | ILE | 184 | SER | 0.000 | 0.159 | -0.159 | 0.159 |
| 256 | SER | 257 | THR | 0.445 | 0.286 | 0.158 | 0.158 |
| 59 | PRO | 138 | THR | 2.121 | 2.279 | -0.157 | 0.157 |
| 128 | CYS | 129 | HIS | 0.528 | 0.684 | -0.156 | 0.156 |
| 289 | ASN | 292 | LEU | 0.578 | 0.422 | 0.155 | 0.155 |
| 342 | THR | 343 | GLU | 0.155 | 0.000 | 0.155 | 0.155 |
| 193 | LEU | 287 | VAL | 0.531 | 0.684 | -0.153 | 0.153 |
| 282 | TYR | 305 | CYS | 2.931 | 2.779 | 0.152 | 0.152 |
| 185 | ARG | 186 | ASN | 0.252 | 0.101 | 0.152 | 0.152 |
| 35 | ILE | 311 | LEU | 1.227 | 1.076 | 0.151 | 0.151 |
| 29 | ILE | 83 | ILE | 0.422 | 0.570 | -0.148 | 0.148 |
| 40 | ILE | 75 | LEU | 1.743 | 1.891 | -0.147 | 0.147 |
| 278 | LEU | 315 | ILE | 0.152 | 0.007 | 0.146 | 0.146 |
| 288 | VAL | 292 | LEU | 1.308 | 1.165 | 0.143 | 0.143 |
| 204 | MET | 205 | ILE | 0.142 | 0.000 | 0.142 | 0.142 |
| 133 | ALA | 137 | CYS | 0.531 | 0.389 | 0.142 | 0.142 |
| 221 | ASN | 222 | PRO | 0.241 | 0.104 | 0.136 | 0.136 |
| 103 | TYR | 157 | CYS | 4.816 | 4.952 | -0.136 | 0.136 |
| 121 | ILE | 125 | ILE | 0.538 | 0.673 | -0.136 | 0.136 |
| 89 | GLY | 176 | VAL | 1.227 | 1.092 | 0.134 | 0.134 |
| 207 | ALA | 212 | GLY | 0.165 | 0.031 | 0.134 | 0.134 |
| 200 | TYR | 201 | VAL | 0.393 | 0.260 | 0.133 | 0.133 |
| 207 | ALA | 211 | TYR | 0.355 | 0.223 | 0.132 | 0.132 |
| 156 | TYR | 160 | TRP | 0.129 | 0.000 | 0.129 | 0.129 |
| 127 | ILE | 217 | ILE | 0.166 | 0.037 | 0.129 | 0.129 |
| 58 | THR | 59 | PRO | 1.011 | 1.139 | -0.128 | 0.128 |
| 26 | VAL | 30 | LEU | 0.613 | 0.741 | -0.127 | 0.127 |
| 100 | CYS | 161 | PHE | 0.258 | 0.383 | -0.125 | 0.125 |
| 282 | TYR | 286 | VAL | 2.407 | 2.531 | -0.124 | 0.124 |
| 166 | LEU | 177 | ILE | 0.816 | 0.939 | -0.123 | 0.123 |
| 32 | VAL | 303 | LEU | 0.123 | 0.000 | 0.123 | 0.123 |
| 29 | ILE | 33 | LEU | 0.797 | 0.920 | -0.122 | 0.122 |
| 20 | VAL | 24 | TYR | 2.240 | 2.361 | -0.121 | 0.121 |
| 186 | ASN | 289 | ASN | 0.119 | 0.000 | 0.119 | 0.119 |
| 98 | CYS | 102 | THR | 0.119 | 0.000 | 0.119 | 0.119 |
| 93 | TYR | 98 | CYS | 0.000 | 0.119 | -0.119 | 0.119 |
| 390 | ALA | 391 | SER | 0.119 | 0.000 | 0.119 | 0.119 |
| 46 | VAL | 65 | VAL | 0.000 | 0.118 | -0.118 | 0.118 |
| 194 | MET | 198 | VAL | 0.254 | 0.371 | -0.117 | 0.117 |
| 123 | ARG | 261 | ARG | 0.000 | 0.115 | -0.115 | 0.115 |
| 58 | THR | 61 | ASN | 3.926 | 3.812 | 0.114 | 0.114 |
| 218 | LEU | 268 | LEU | 0.112 | 0.000 | 0.112 | 0.112 |
| 285 | LEU | 302 | LEU | 0.739 | 0.850 | -0.111 | 0.111 |
| 307 | ILE | 310 | TYR | 0.000 | 0.110 | -0.110 | 0.110 |
| 84 | THR | 88 | TYR | 0.171 | 0.282 | -0.110 | 0.110 |
| 281 | PRO | 308 | CYS | 0.276 | 0.167 | 0.109 | 0.109 |
| 59 | PRO | 142 | ALA | 1.774 | 1.665 | 0.109 | 0.109 |
| 43 | ASN | 316 | ASN | 0.000 | 0.108 | -0.108 | 0.108 |
| 97 | GLY | 102 | THR | 0.330 | 0.222 | 0.108 | 0.108 |
| 106 | TYR | 110 | ASN | 0.107 | 0.000 | 0.107 | 0.107 |
| 195 | ASP | 200 | TYR | 0.637 | 0.530 | 0.107 | 0.107 |
| 117 | THR | 202 | VAL | 0.104 | 0.000 | 0.104 | 0.104 |
| 294 | SER | 295 | PRO | 0.319 | 0.423 | -0.104 | 0.104 |
| 184 | SER | 186 | ASN | 0.339 | 0.236 | 0.103 | 0.103 |
| 106 | TYR | 282 | TYR | 0.695 | 0.594 | 0.102 | 0.102 |
| 169 | SER | 174 | ALA | 0.374 | 0.475 | -0.101 | 0.101 |
| 106 | TYR | 109 | ILE | 0.000 | 0.100 | -0.100 | 0.100 |
| 98 | CYS | 180 | GLY | 0.297 | 0.199 | 0.098 | 0.098 |
| 125 | ILE | 132 | LYS | 0.000 | 0.096 | -0.096 | 0.096 |
| 49 | VAL | 334 | LEU | 0.897 | 0.801 | 0.096 | 0.096 |
| 172 | LYS | 173 | ASP | 1.428 | 1.523 | -0.095 | 0.095 |
| 284 | THR | 288 | VAL | 0.351 | 0.445 | -0.094 | 0.094 |
| 200 | TYR | 283 | ARG | 1.116 | 1.023 | 0.093 | 0.093 |
| 32 | VAL | 37 | GLY | 0.070 | 0.162 | -0.092 | 0.092 |
| 22 | LEU | 25 | GLN | 0.395 | 0.487 | -0.091 | 0.091 |
| 192 | TYR | 290 | SER | 0.346 | 0.437 | -0.091 | 0.091 |
| 363 | PHE | 365 | THR | 0.089 | 0.000 | 0.089 | 0.089 |
| 113 | SER | 200 | TYR | 0.000 | 0.089 | -0.089 | 0.089 |
| 75 | LEU | 313 | SER | 1.769 | 1.682 | 0.088 | 0.088 |
| 118 | ALA | 145 | ILE | 0.357 | 0.444 | -0.088 | 0.088 |
| 345 | PRO | 346 | ALA | 0.000 | 0.087 | -0.087 | 0.087 |
| 188 | TYR | 191 | ILE | 0.085 | 0.000 | 0.085 | 0.085 |
| 204 | MET | 208 | THR | 0.084 | 0.000 | 0.084 | 0.084 |
| 15 | GLN | 16 | PRO | 0.841 | 0.758 | 0.084 | 0.084 |
| 170 | THR | 175 | ILE | 0.388 | 0.305 | 0.083 | 0.083 |
| 243 | THR | 244 | ASN | 0.083 | 0.000 | 0.083 | 0.083 |
| 52 | ARG | 53 | THR | 0.000 | 0.081 | -0.081 | 0.081 |
| 98 | CYS | 165 | ASP | 1.062 | 0.981 | 0.081 | 0.081 |
| 21 | ALA | 24 | TYR | 0.000 | 0.079 | -0.079 | 0.079 |
| 32 | VAL | 79 | GLY | 1.476 | 1.555 | -0.079 | 0.079 |
| 47 | VAL | 68 | ALA | 0.366 | 0.445 | -0.079 | 0.079 |
| 84 | THR | 89 | GLY | 0.264 | 0.186 | 0.078 | 0.078 |
| 81 | PRO | 84 | THR | 0.211 | 0.133 | 0.078 | 0.078 |
| 323 | MET | 328 | ARG | 0.265 | 0.188 | 0.077 | 0.077 |
| 169 | SER | 175 | ILE | 1.574 | 1.499 | 0.075 | 0.075 |
| 124 | TYR | 125 | ILE | 0.333 | 0.259 | 0.073 | 0.073 |
| 103 | TYR | 104 | LEU | 1.054 | 0.983 | 0.071 | 0.071 |
| 91 | TRP | 178 | SER | 1.028 | 0.957 | 0.071 | 0.071 |
| 164 | LEU | 179 | CYS | 0.000 | 0.071 | -0.071 | 0.071 |
| 254 | PHE | 255 | ASN | 0.318 | 0.388 | -0.070 | 0.070 |
| 211 | TYR | 320 | TYR | 0.068 | 0.000 | 0.068 | 0.068 |
| 229 | GLU | 230 | ASN | 0.000 | 0.067 | -0.067 | 0.067 |
| 211 | TYR | 214 | ILE | 0.933 | 0.866 | 0.067 | 0.067 |
| 162 | PHE | 163 | LEU | 0.067 | 0.000 | 0.067 | 0.067 |
| 53 | THR | 56 | MET | 2.222 | 2.288 | -0.066 | 0.066 |
| 264 | VAL | 267 | MET | 0.000 | 0.066 | -0.066 | 0.066 |
| 153 | THR | 154 | SER | 0.000 | 0.065 | -0.065 | 0.065 |
| 168 | ILE | 177 | ILE | 0.084 | 0.020 | 0.064 | 0.064 |
| 36 | CYS | 40 | ILE | 0.074 | 0.136 | -0.063 | 0.063 |
| 194 | MET | 199 | PHE | 0.107 | 0.045 | 0.062 | 0.062 |
| 168 | ILE | 176 | VAL | 1.444 | 1.506 | -0.062 | 0.062 |
| 47 | VAL | 51 | MET | 0.407 | 0.347 | 0.060 | 0.060 |
| 44 | ILE | 48 | LEU | 0.950 | 0.890 | 0.059 | 0.059 |
| 84 | THR | 90 | SER | 0.056 | 0.000 | 0.056 | 0.056 |
| 387 | THR | 389 | LEU | 0.000 | 0.056 | -0.056 | 0.056 |
| 104 | LEU | 107 | LEU | 0.057 | 0.002 | 0.056 | 0.056 |
| 77 | ALA | 104 | LEU | 1.130 | 1.184 | -0.054 | 0.054 |
| 65 | VAL | 69 | VAL | 0.167 | 0.114 | 0.053 | 0.053 |
| 17 | ARG | 173 | ASP | 0.000 | 0.051 | -0.051 | 0.051 |
| 264 | VAL | 268 | LEU | 0.386 | 0.437 | -0.050 | 0.050 |
| 304 | PHE | 305 | CYS | 0.195 | 0.145 | 0.050 | 0.050 |
| 99 | LEU | 161 | PHE | 4.339 | 4.387 | -0.048 | 0.048 |
| 74 | VAL | 78 | ALA | 0.029 | 0.076 | -0.048 | 0.048 |
| 188 | TYR | 290 | SER | 0.047 | 0.000 | 0.047 | 0.047 |
| 22 | LEU | 26 | VAL | 0.496 | 0.449 | 0.047 | 0.047 |
| 80 | LEU | 81 | PRO | 0.770 | 0.817 | -0.047 | 0.047 |
| 160 | TRP | 195 | ASP | 0.000 | 0.046 | -0.046 | 0.046 |
| 63 | TYR | 115 | SER | 0.115 | 0.161 | -0.046 | 0.046 |
| 165 | ASP | 166 | LEU | 0.213 | 0.168 | 0.045 | 0.045 |
| 271 | VAL | 319 | ILE | 0.945 | 0.989 | -0.045 | 0.045 |
| 344 | LYS | 345 | PRO | 0.229 | 0.273 | -0.044 | 0.044 |
| 106 | TYR | 157 | CYS | 1.423 | 1.467 | -0.044 | 0.044 |
| 50 | VAL | 327 | PHE | 0.044 | 0.000 | 0.044 | 0.044 |
| 71 | ASP | 317 | PRO | 0.043 | 0.000 | 0.043 | 0.043 |
| 114 | CYS | 153 | THR | 0.583 | 0.626 | -0.043 | 0.043 |
| 254 | PHE | 376 | TYR | 0.000 | 0.042 | -0.042 | 0.042 |
| 186 | ASN | 187 | TYR | 0.000 | 0.040 | -0.040 | 0.040 |
| 83 | ILE | 87 | ILE | 0.491 | 0.530 | -0.039 | 0.039 |
| 112 | SER | 275 | PHE | 0.000 | 0.038 | -0.038 | 0.038 |
| 367 | LEU | 368 | ASP | 0.000 | 0.035 | -0.035 | 0.035 |
| 91 | TRP | 98 | CYS | 5.900 | 5.935 | -0.035 | 0.035 |
| 72 | LEU | 77 | ALA | 0.033 | 0.000 | 0.033 | 0.033 |
| 165 | ASP | 179 | CYS | 1.081 | 1.111 | -0.030 | 0.030 |
| 161 | PHE | 162 | PHE | 0.000 | 0.029 | -0.029 | 0.029 |
| 275 | PHE | 280 | MET | 0.000 | 0.029 | -0.029 | 0.029 |
| 114 | CYS | 152 | PHE | 0.000 | 0.028 | -0.028 | 0.028 |
| 46 | VAL | 50 | VAL | 0.027 | 0.000 | 0.027 | 0.027 |
| 102 | THR | 105 | GLN | 0.885 | 0.911 | -0.027 | 0.027 |
| 96 | VAL | 100 | CYS | 0.424 | 0.398 | 0.026 | 0.026 |
| 112 | SER | 313 | SER | 0.026 | 0.000 | 0.026 | 0.026 |
| 127 | ILE | 218 | LEU | 0.000 | 0.025 | -0.025 | 0.025 |
| 39 | GLY | 72 | LEU | 0.000 | 0.024 | -0.024 | 0.024 |
| 48 | LEU | 53 | THR | 0.000 | 0.023 | -0.023 | 0.023 |
| 373 | THR | 374 | ASP | 0.023 | 0.000 | 0.023 | 0.023 |
| 40 | ILE | 44 | ILE | 0.738 | 0.715 | 0.022 | 0.022 |
| 125 | ILE | 130 | PRO | 0.389 | 0.408 | -0.019 | 0.019 |
| 112 | SER | 312 | ASN | 0.018 | 0.000 | 0.018 | 0.018 |
| 146 | ILE | 150 | TRP | 1.326 | 1.344 | -0.018 | 0.018 |
| 122 | GLU | 126 | ALA | 0.000 | 0.018 | -0.018 | 0.018 |
| 202 | VAL | 203 | PRO | 1.479 | 1.496 | -0.016 | 0.016 |
| 327 | PHE | 331 | PHE | 0.006 | 0.022 | -0.016 | 0.016 |
| 253 | CYS | 256 | SER | 0.016 | 0.000 | 0.016 | 0.016 |
| 115 | SER | 146 | ILE | 0.016 | 0.000 | 0.016 | 0.016 |
| 43 | ASN | 314 | ALA | 0.000 | 0.016 | -0.016 | 0.016 |
| 129 | HIS | 130 | PRO | 0.106 | 0.121 | -0.015 | 0.015 |
| 41 | VAL | 45 | MET | 0.000 | 0.015 | -0.015 | 0.015 |
| 34 | ILE | 38 | LEU | 0.587 | 0.572 | 0.015 | 0.015 |
| 98 | CYS | 103 | TYR | 0.014 | 0.000 | 0.014 | 0.014 |
| 85 | ASP | 92 | VAL | 0.014 | 0.000 | 0.014 | 0.014 |
| 140 | SER | 143 | LYS | 0.000 | 0.014 | -0.014 | 0.014 |
| 392 | GLU | 393 | VAL | 0.013 | 0.000 | 0.013 | 0.013 |
| 55 | HIS | 330 | ALA | 0.000 | 0.011 | -0.011 | 0.011 |
| 116 | ILE | 120 | THR | 0.369 | 0.360 | 0.009 | 0.009 |
| 168 | ILE | 175 | ILE | 0.812 | 0.805 | 0.008 | 0.008 |
| 315 | ILE | 318 | VAL | 0.000 | 0.007 | -0.007 | 0.007 |
| 316 | ASN | 317 | PRO | 0.926 | 0.933 | -0.006 | 0.006 |
| 393 | VAL | 394 | SER | 0.006 | 0.000 | 0.006 | 0.006 |
| 210 | LEU | 213 | PHE | 0.006 | 0.000 | 0.006 | 0.006 |
| 39 | GLY | 317 | PRO | 0.000 | 0.005 | -0.005 | 0.005 |
| 123 | ARG | 127 | ILE | 0.005 | 0.000 | 0.005 | 0.005 |
| 5 | THR | 6 | VAL | 0.062 | 0.059 | 0.004 | 0.004 |
| 47 | VAL | 72 | LEU | 0.000 | 0.003 | -0.003 | 0.003 |
| 260 | SER | 261 | ARG | 0.156 | 0.153 | 0.003 | 0.003 |
| 145 | ILE | 149 | VAL | 0.184 | 0.186 | -0.002 | 0.002 |
| 167 | ASN | 176 | VAL | 0.754 | 0.756 | -0.002 | 0.002 |
| 106 | TYR | 195 | ASP | 0.000 | 0.001 | -0.001 | 0.001 |
| 372 | VAL | 373 | THR | 0.000 | 0.000 | 0.000 | 0.000 |
RRCS change distribution
Magnitude classification
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| ≥ 2.39, 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