GPCompReports

TRFR

Gene TRHR Thyrotropin-releasing hormone receptors Peptide receptors UniProt P34981
756
Total Contact Pairs
77
Significant Changes
18.39
Max Increase
-8.26
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.

ICL1 K54 12.48x48 K54 12.48x48 K H55 12.49x49 H55 12.49x49 H M56 12.50x50 M56 12.50x50 M R57 12.51x51 R57 12.51x51 R ICL1ECL1 G89 G89 G S90 23.49x49 S90 23.49x49 S W91 23.50x50 W91 23.50x50 W V92 23.51x51 V92 23.51x51 V Y93 23.52x52 Y93 23.52x52 Y ECL1ICL2 P130 34.50x50 P130 34.50x50 P I131 34.51x51 I131 34.51x51 I K132 34.52x52 K132 34.52x52 K A133 34.53x53 A133 34.53x53 A Q134 34.54x54 Q134 34.54x54 Q F135 34.55x55 F135 34.55x55 F L136 34.56x56 L136 34.56x56 L C137 34.57x57 C137 34.57x57 C ICL2ECL2 D165 D165 D L166 L166 L N167 N167 N I168 I168 I S169 S169 S T170 T170 T Y171 Y171 Y K172 K172 K D173 D173 D A174 A174 A I175 I175 I V176 V176 V I177 I177 I S178 S178 S C179 45.50x50 C179 45.50x50 C G180 45.51x51 G180 45.51x51 G Y181 45.52x52 Y181 45.52x52 Y K182 K182 K ECL2ICL3 N230 N230 N S231 S231 S K232 K232 K T233 T233 T W234 W234 W K235 K235 K N236 N236 N D237 D237 D S238 S238 S T239 T239 T H240 H240 H Q241 Q241 Q N242 N242 N T243 T243 T N244 N244 N L245 L245 L N246 N246 N V247 V247 V N248 N248 N T249 T249 T S250 S250 S N251 N251 N R252 R252 R C253 C253 C F254 F254 F ICL3ECL3 S293 S293 S S294 S294 S P295 P295 P F296 F296 F Q297 Q297 Q ECL3N-term M1 M1 M E2 E2 E N3 N3 N E4 E4 E T5 T5 T V6 V6 V S7 S7 S E8 E8 E L9 L9 L N10 N10 N Q11 Q11 Q T12 T12 T Q13 Q13 Q L14 L14 L Q15 Q15 Q P16 P16 P R17 R17 R A18 A18 A V19 V19 V V20 V20 V A21 A21 A N-termC-term C337 C337 C K338 K338 K Q339 Q339 Q K340 K340 K P341 P341 P T342 T342 T E343 E343 E K344 K344 K P345 P345 P A346 A346 A N347 N347 N Y348 Y348 Y S349 S349 S V350 V350 V A351 A351 A L352 L352 L N353 N353 N Y354 Y354 Y S355 S355 S V356 V356 V I357 I357 I K358 K358 K E359 E359 E S360 S360 S D361 D361 D H362 H362 H F363 F363 F S364 S364 S T365 T365 T E366 E366 E L367 L367 L D368 D368 D D369 D369 D I370 I370 I T371 T371 T V372 V372 V T373 T373 T D374 D374 D T375 T375 T Y376 Y376 Y L377 L377 L S378 S378 S A379 A379 A T380 T380 T K381 K381 K V382 V382 V S383 S383 S F384 F384 F D385 D385 D D386 D386 D T387 T387 T C388 C388 C L389 L389 L A390 A390 A S391 S391 S E392 E392 E V393 V393 V S394 S394 S F395 F395 F S396 S396 S Q397 Q397 Q S398 S398 S C-term L22 1.29x29 L22 1.29x29 L E23 1.30x30 E23 1.30x30 E Y24 1.31x31 Y24 1.31x31 Y Q25 1.32x32 Q25 1.32x32 Q V26 1.33x33 V26 1.33x33 V V27 1.34x34 V27 1.34x34 V T28 1.35x35 T28 1.35x35 T I29 1.36x36 I29 1.36x36 I L30 1.37x37 L30 1.37x37 L L31 1.38x38 L31 1.38x38 L V32 1.39x39 V32 1.39x39 V L33 1.40x40 L33 1.40x40 L I34 1.41x41 I34 1.41x41 I I35 1.42x42 I35 1.42x42 I C36 1.43x43 C36 1.43x43 C G37 1.44x44 G37 1.44x44 G L38 1.45x45 L38 1.45x45 L G39 1.46x46 G39 1.46x46 G I40 1.47x47 I40 1.47x47 I V41 1.48x48 V41 1.48x48 V G42 1.49x49 G42 1.49x49 G N43 1.50x50 N43 1.50x50 N I44 1.51x51 I44 1.51x51 I M45 1.52x52 M45 1.52x52 M V46 1.53x53 V46 1.53x53 V V47 1.54x54 V47 1.54x54 V L48 1.55x55 L48 1.55x55 L V49 1.56x56 V49 1.56x56 V V50 1.57x57 V50 1.57x57 V M51 1.58x58 M51 1.58x58 M R52 1.59x59 R52 1.59x59 R T53 1.60x60 T53 1.60x60 T T58 2.37x37 T58 2.37x37 T P59 2.38x38 P59 2.38x38 P T60 2.39x39 T60 2.39x39 T N61 2.40x40 N61 2.40x40 N C62 2.41x41 C62 2.41x41 C Y63 2.42x42 Y63 2.42x42 Y L64 2.43x43 L64 2.43x43 L V65 2.44x44 V65 2.44x44 V S66 2.45x45 S66 2.45x45 S L67 2.46x46 L67 2.46x46 L A68 2.47x47 A68 2.47x47 A V69 2.48x48 V69 2.48x48 V A70 2.49x49 A70 2.49x49 A D71 2.50x50 D71 2.50x50 D L72 2.51x51 L72 2.51x51 L M73 2.52x52 M73 2.52x52 M V74 2.53x53 V74 2.53x53 V L75 2.54x54 L75 2.54x54 L V76 2.55x55 V76 2.55x55 V A77 2.56x551 A77 2.56x551 A A78 2.57x56 A78 2.57x56 A G79 2.58x57 G79 2.58x57 G L80 2.59x58 L80 2.59x58 L P81 2.60x59 P81 2.60x59 P N82 2.61x60 N82 2.61x60 N I83 2.62x61 I83 2.62x61 I T84 2.63x62 T84 2.63x62 T D85 2.64x63 D85 2.64x63 D S86 2.65x64 S86 2.65x64 S I87 2.66x65 I87 2.66x65 I Y88 2.67x66 Y88 2.67x66 Y G94 3.21x21 G94 3.21x21 G Y95 3.22x22 Y95 3.22x22 Y V96 3.23x23 V96 3.23x23 V G97 3.24x24 G97 3.24x24 G C98 3.25x25 C98 3.25x25 C L99 3.26x26 L99 3.26x26 L C100 3.27x27 C100 3.27x27 C I101 3.28x28 I101 3.28x28 I T102 3.29x29 T102 3.29x29 T Y103 3.30x30 Y103 3.30x30 Y L104 3.31x31 L104 3.31x31 L Q105 3.32x32 Q105 3.32x32 Q Y106 3.33x33 Y106 3.33x33 Y L107 3.34x34 L107 3.34x34 L G108 3.35x35 G108 3.35x35 G I109 3.36x36 I109 3.36x36 I N110 3.37x37 N110 3.37x37 N A111 3.38x38 A111 3.38x38 A S112 3.39x39 S112 3.39x39 S S113 3.40x40 S113 3.40x40 S C114 3.41x41 C114 3.41x41 C S115 3.42x42 S115 3.42x42 S I116 3.43x43 I116 3.43x43 I T117 3.44x44 T117 3.44x44 T A118 3.45x45 A118 3.45x45 A F119 3.46x46 F119 3.46x46 F T120 3.47x47 T120 3.47x47 T I121 3.48x48 I121 3.48x48 I E122 3.49x49 E122 3.49x49 E R123 3.50x50 R123 3.50x50 R Y124 3.51x51 Y124 3.51x51 Y I125 3.52x52 I125 3.52x52 I A126 3.53x53 A126 3.53x53 A I127 3.54x54 I127 3.54x54 I C128 3.55x55 C128 3.55x55 C H129 3.56x56 H129 3.56x56 H T138 4.38x38 T138 4.38x38 T F139 4.39x39 F139 4.39x39 F S140 4.40x40 S140 4.40x40 S R141 4.41x41 R141 4.41x41 R A142 4.42x42 A142 4.42x42 A K143 4.43x43 K143 4.43x43 K K144 4.44x44 K144 4.44x44 K I145 4.45x45 I145 4.45x45 I I146 4.46x46 I146 4.46x46 I I147 4.47x47 I147 4.47x47 I F148 4.48x48 F148 4.48x48 F V149 4.49x49 V149 4.49x49 V W150 4.50x50 W150 4.50x50 W A151 4.51x51 A151 4.51x51 A F152 4.52x52 F152 4.52x52 F T153 4.53x53 T153 4.53x53 T S154 4.54x54 S154 4.54x54 S L155 4.55x55 L155 4.55x55 L Y156 4.56x56 Y156 4.56x56 Y C157 4.57x57 C157 4.57x57 C M158 4.58x58 M158 4.58x58 M L159 4.59x59 L159 4.59x59 L W160 4.60x60 W160 4.60x60 W F161 4.61x61 F161 4.61x61 F F162 4.62x62 F162 4.62x62 F L163 4.63x63 L163 4.63x63 L L164 4.64x64 L164 4.64x64 L I183 5.30x30 I183 5.30x30 I S184 5.31x31 S184 5.31x31 S R185 5.32x32 R185 5.32x32 R N186 5.33x33 N186 5.33x33 N Y187 5.34x34 Y187 5.34x34 Y Y188 5.35x35 Y188 5.35x35 Y S189 5.36x36 S189 5.36x36 S P190 5.37x37 P190 5.37x37 P I191 5.38x38 I191 5.38x38 I Y192 5.39x39 Y192 5.39x39 Y L193 5.40x40 L193 5.40x40 L M194 5.41x41 M194 5.41x41 M D195 5.42x42 D195 5.42x42 D F196 5.43x43 F196 5.43x43 F G197 5.44x44 G197 5.44x44 G V198 5.45x45 V198 5.45x45 V F199 5.46x46 F199 5.46x46 F Y200 5.47x47 Y200 5.47x47 Y V201 5.48x48 V201 5.48x48 V V202 5.49x49 V202 5.49x49 V P203 5.50x50 P203 5.50x50 P M204 5.51x51 M204 5.51x51 M I205 5.52x52 I205 5.52x52 I L206 5.53x53 L206 5.53x53 L A207 5.54x54 A207 5.54x54 A T208 5.55x55 T208 5.55x55 T V209 5.56x56 V209 5.56x56 V L210 5.57x57 L210 5.57x57 L Y211 5.58x58 Y211 5.58x58 Y G212 5.59x59 G212 5.59x59 G F213 5.60x60 F213 5.60x60 F I214 5.61x61 I214 5.61x61 I A215 5.62x62 A215 5.62x62 A R216 5.63x63 R216 5.63x63 R I217 5.64x64 I217 5.64x64 I L218 5.65x65 L218 5.65x65 L F219 5.66x66 F219 5.66x66 F L220 5.67x67 L220 5.67x67 L N221 5.68x68 N221 5.68x68 N P222 5.69x69 P222 5.69x69 P I223 5.70x70 I223 5.70x70 I P224 5.71x71 P224 5.71x71 P S225 5.72x72 S225 5.72x72 S D226 5.73x73 D226 5.73x73 D P227 5.74x74 P227 5.74x74 P K228 5.75x75 K228 5.75x75 K E229 5.76x76 E229 5.76x76 E N255 6.24x24 N255 6.24x24 N S256 6.25x25 S256 6.25x25 S T257 6.26x26 T257 6.26x26 T V258 6.27x27 V258 6.27x27 V S259 6.28x28 S259 6.28x28 S S260 6.29x29 S260 6.29x29 S R261 6.30x30 R261 6.30x30 R K262 6.31x31 K262 6.31x31 K Q263 6.32x32 Q263 6.32x32 Q V264 6.33x33 V264 6.33x33 V T265 6.34x34 T265 6.34x34 T K266 6.35x35 K266 6.35x35 K M267 6.36x36 M267 6.36x36 M L268 6.37x37 L268 6.37x37 L A269 6.38x38 A269 6.38x38 A V270 6.39x39 V270 6.39x39 V V271 6.40x40 V271 6.40x40 V V272 6.41x41 V272 6.41x41 V I273 6.42x42 I273 6.42x42 I L274 6.43x43 L274 6.43x43 L F275 6.44x44 F275 6.44x44 F A276 6.45x45 A276 6.45x45 A L277 6.46x46 L277 6.46x46 L L278 6.47x47 L278 6.47x47 L W279 6.48x48 W279 6.48x48 W M280 6.49x49 M280 6.49x49 M P281 6.50x50 P281 6.50x50 P Y282 6.51x51 Y282 6.51x51 Y R283 6.52x52 R283 6.52x52 R T284 6.53x53 T284 6.53x53 T L285 6.54x54 L285 6.54x54 L V286 6.55x55 V286 6.55x55 V V287 6.56x56 V287 6.56x56 V V288 6.57x57 V288 6.57x57 V N289 6.58x58 N289 6.58x58 N S290 6.59x59 S290 6.59x59 S F291 6.60x60 F291 6.60x60 F L292 6.61x61 L292 6.61x61 L E298 7.31x30 E298 7.31x30 E N299 7.32x31 N299 7.32x31 N W300 7.33x32 W300 7.33x32 W F301 7.34x33 F301 7.34x33 F L302 7.35x34 L302 7.35x34 L L303 7.36x35 L303 7.36x35 L F304 7.37x36 F304 7.37x36 F C305 7.38x37 C305 7.38x37 C R306 7.39x38 R306 7.39x38 R I307 7.40x39 I307 7.40x39 I C308 7.41x40 C308 7.41x40 C I309 7.42x41 I309 7.42x41 I Y310 7.43x42 Y310 7.43x42 Y L311 7.44x43 L311 7.44x43 L N312 7.45x45 N312 7.45x45 N S313 7.46x46 S313 7.46x46 S A314 7.47x47 A314 7.47x47 A I315 7.48x48 I315 7.48x48 I N316 7.49x49 N316 7.49x49 N P317 7.50x50 P317 7.50x50 P V318 7.51x51 V318 7.51x51 V I319 7.52x52 I319 7.52x52 I Y320 7.53x53 Y320 7.53x53 Y N321 7.54x54 N321 7.54x54 N L322 7.55x55 L322 7.55x55 L M323 7.56x56 M323 7.56x56 M S324 8.47x47 S324 8.47x47 S Q325 8.48x48 Q325 8.48x48 Q K326 8.49x49 K326 8.49x49 K F331 8.54x54 F331 8.54x54 F R332 8.55x55 R332 8.55x55 R K333 8.56x56 K333 8.56x56 K F327 8.50x50 F327 8.50x50 F R328 8.51x51 R328 8.51x51 R A329 8.52x52 A329 8.52x52 A A330 8.53x53 A330 8.53x53 A L334 8.57x57 L334 8.57x57 L C335 8.58x58 C335 8.58x58 C N336 8.59x59 N336 8.59x59 N

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)).

Per-segment summary
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

-0.01
Mean ΔRRCS
1.72
Std Dev
-0.04
Median

Magnitude classification

17
High (|Δ| ≥ 5.0)
60
Medium (2.4 ≤ |Δ| < 5.0)
679
Low (|Δ| < 2.4)

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