ACM2

Gene CHRM2 Acetylcholine receptors (muscarinic) Aminergic receptors UniProt P08172

UniProt ↗ GPCRdb ↗ NCBI Gene ↗

746

Total Contact Pairs

Significant Changes

9.95

Max Increase

-6.80

Max Decrease

Interactive snake plot

GPCRdb-style topology. Click the view buttons to recolor residues by different data layers. Toggle contact links to draw significant residue-residue contacts as arcs. Click loop labels (ICL/ECL) to expand or collapse loop regions.

Color convention: blue = active-favoring, red = inactive-favoring.

Top 100 conformational changes

Residue pairs with the largest RRCS changes between active and inactive states. GPCRdb numbering in parentheses. Highlighted rows exceed the significance threshold.

Rank	Residue 1	Residue 2	Active RRCS	Inactive RRCS	ΔRRCS	Magnitude
1	GLU272	ASN273	9.954	0.000	+9.954	HIGH
2	LYS316	ASP317	9.185	0.000	+9.185	HIGH
3	HIS257	ASN258	8.654	0.000	+8.654	HIGH
4	GLN261	ASN262	8.725	0.073	+8.652	HIGH
5	ARG267	ASP268	7.928	0.000	+7.928	HIGH
6	ASN58 (2.39x39)	ARG135 (34.57x57)	8.851	0.982	+7.870	HIGH
7	ASN244	ASN245	7.474	0.000	+7.474	HIGH
8	ASN58 (2.39x39)	ARG121 (3.50x50)	0.000	6.796	-6.796	HIGH
9	PRO132 (34.54x54)	LYS280	0.000	6.114	-6.114	HIGH
10	ASP97 (3.26x26)	ARG169	7.168	1.110	+6.058	HIGH
11	GLU318	ASN319	5.647	0.000	+5.647	HIGH
12	ASP120 (3.49x49)	ARG121 (3.50x50)	0.000	5.420	-5.420	HIGH
13	TYR403 (6.51x51)	TYR426 (7.39x38)	2.853	8.109	-5.256	HIGH
14	GLN276	ARG381 (6.29x29)	0.000	5.238	-5.238	HIGH
15	ARG121 (3.50x50)	TYR440 (7.53x53)	5.022	0.000	+5.022	HIGH
16	ILE417	TRP422 (7.35x34)	1.104	5.665	-4.561	MED
17	PHE181	THR187 (5.39x40)	3.578	8.037	-4.460	MED
18	TRP400 (6.48x48)	ASN432 (7.45x45)	7.094	2.663	+4.432	MED
19	ARG121 (3.50x50)	TYR206 (5.58x58)	4.431	0.000	+4.431	MED
20	SER309	THR310	4.413	0.000	+4.413	MED
21	SER250	ASP253	0.000	4.353	-4.353	MED
22	TYR104 (3.33x33)	TYR426 (7.39x38)	4.377	0.105	+4.271	MED
23	ASN258	LYS259	4.216	0.000	+4.216	MED
24	LEU114 (3.43x43)	TYR440 (7.53x53)	4.079	0.000	+4.079	MED
25	ASN262	GLU278	0.000	4.053	-4.053	MED
26	THR388 (6.36x36)	CYS443 (7.56x56)	0.838	4.811	-3.973	MED
27	ALA441 (7.54x54)	PHE447 (8.50x50)	4.300	0.360	+3.940	MED
28	GLU272	ARG381 (6.29x29)	0.000	3.765	-3.765	MED
29	TYR80 (2.61x60)	TYR426 (7.39x38)	11.187	7.469	+3.718	MED
30	TYR196 (5.48x48)	ASN404 (6.52x52)	1.709	5.373	-3.663	MED
31	TYR104 (3.33x33)	TYR403 (6.51x51)	4.221	0.598	+3.622	MED
32	TYR426 (7.39x38)	TYR430 (7.43x42)	3.808	0.264	+3.544	MED
33	VAL344	GLU345	0.000	3.527	-3.527	MED
34	PHE396 (6.44x44)	TRP400 (6.48x48)	4.371	7.893	-3.522	MED
35	GLN163 (4.65x65)	VAL168	1.361	4.863	-3.502	MED
36	LEU154 (4.56x56)	TRP155 (4.57x57)	3.840	0.389	+3.451	MED
37	ASN58 (2.39x39)	ASP120 (3.49x49)	4.255	0.851	+3.404	MED
38	THR170	GLN179	3.713	7.054	-3.341	MED
39	SER118 (3.47x47)	TYR206 (5.58x58)	5.045	1.706	+3.338	MED
40	TYR131 (34.53x53)	ARG135 (34.57x57)	3.297	0.000	+3.297	MED
41	ASP103 (3.32x32)	TYR426 (7.39x38)	3.279	0.000	+3.279	MED
42	LYS219 (5.71x71)	ASP304	0.000	3.269	-3.269	MED
43	GLU256	HIS257	3.213	0.000	+3.213	MED
44	PHE181	THR190 (5.42x43)	0.000	3.198	-3.198	MED
45	PHE188 (5.40x41)	PHE412 (6.60x60)	3.112	0.000	+3.112	MED
46	ALA441 (7.54x54)	LYS448 (8.51x51)	0.000	3.112	-3.112	MED
47	ALA395 (6.43x43)	ASN432 (7.45x45)	0.168	3.276	-3.109	MED
48	SER334	ASP335	3.028	0.000	+3.028	MED
49	ASN273	ARG381 (6.29x29)	0.000	3.024	-3.024	MED
50	PHE188 (5.40x41)	ILE192	0.071	3.022	-2.951	MED
51	VAL168	GLN179	0.100	3.026	-2.926	MED
52	TYR403 (6.51x51)	VAL407	3.818	0.905	+2.913	MED
53	SER8	ASN9	0.000	2.909	-2.909	MED
54	GLN163 (4.65x65)	ARG169	2.148	5.034	-2.886	MED
55	ILE260	GLN261	2.873	0.000	+2.873	MED
56	MET406	TRP422 (7.35x34)	3.974	6.832	-2.858	MED
57	VAL270	THR271	2.849	0.000	+2.849	MED
58	GLU279	LYS280	2.824	0.000	+2.824	MED
59	PHE180	PHE181	1.577	4.374	-2.798	MED
60	ILE217	GLU382	2.748	0.000	+2.748	MED
61	ASP69	SER110	2.773	0.029	+2.744	MED
62	SER76	TYR430 (7.43x42)	7.178	4.473	+2.704	MED
63	LYS214	GLU382	2.645	0.000	+2.645	MED
64	ARG169	VAL171	0.773	3.416	-2.644	MED
65	PRO437	LEU442	2.633	0.000	+2.633	MED
66	VAL171	TYR177	8.820	6.279	+2.542	MED
67	TYR206 (5.58x58)	LEU393	2.024	4.543	-2.519	MED
68	ASN108	ALA194	2.602	0.087	+2.515	MED
69	HIS53	ASN273	0.000	2.497	-2.497	MED
70	ASP120 (3.49x49)	ARG135 (34.57x57)	4.197	1.703	+2.494	MED
71	VAL44	TYR440 (7.53x53)	0.000	2.493	-2.493	MED
72	ILE392	CYS439	2.456	0.008	+2.448	MED
73	GLN163 (4.65x65)	GLN179	5.431	2.984	+2.447	MED
74	THR399	LEU428	8.609	6.172	+2.437	MED
75	PHE180	THR187 (5.39x40)	2.436	0.000	+2.436	MED
76	LYS452	MET456	0.929	3.360	-2.431	MED
77	TRP99	LEU100	2.807	0.384	+2.423	MED
78	PRO266	ARG267	2.420	0.000	+2.420	MED
79	ILE117	ILE389	0.000	2.419	-2.419	MED
80	LEU43	PHE451	5.669	3.269	+2.400	MED
81	ARG121 (3.50x50)	ARG135 (34.57x57)	0.000	2.385	-2.385	MED
82	THR310	SER311	2.377	0.000	+2.377	MED
83	LEU65	ASN113	2.436	0.068	+2.367	MED
84	LEU255	PRO266	0.000	2.330	-2.330	MED
85	TYR403 (6.51x51)	TRP422 (7.35x34)	0.694	2.985	-2.292	MED
86	ILE117	ARG121 (3.50x50)	2.359	0.098	+2.262	MED
87	ASN306	THR307	2.228	0.000	+2.228	MED
88	TRP162	GLN179	5.218	2.995	+2.223	MED
89	THR56	ASN273	0.000	2.194	-2.194	LOW
90	ARG121 (3.50x50)	CYS124	0.000	2.187	-2.187	LOW
91	LEU115	PRO198	0.851	3.010	-2.158	LOW
92	TYR440 (7.53x53)	PHE447 (8.50x50)	0.000	2.147	-2.147	LOW
93	ASN245	ASN246	2.123	0.000	+2.123	LOW
94	ASN58 (2.39x39)	VAL385	0.000	2.116	-2.116	LOW
95	TRP162	ASN183	2.112	0.000	+2.112	LOW
96	PRO93	ARG169	7.713	5.608	+2.105	LOW
97	ARG52	THR271	0.000	2.099	-2.099	LOW
98	ILE301	GLU305	0.000	2.086	-2.086	LOW
99	PHE396 (6.44x44)	ASN432 (7.45x45)	1.967	4.052	-2.085	LOW
100	LEU65	LEU114 (3.43x43)	2.468	0.405	+2.063	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| ≥ 2.21 are shown (per-receptor significance threshold = max(mean(|Δ|) + σ, 0.2)).

Segment	Range	Active-favoring residues	Count	Inactive-favoring residues	Count
TM1	-	-	0	-	0
TM2	58-80	58 (7.9), 80 (3.7)	2	-	0
TM3	97-121	97 (6.1), 104 (4.3), 114 (4.1), 118 (3.3), 103 (3.3)	5	121 (-6.8), 120 (-5.4)	2
TM4	154-163	154 (3.5), 155 (3.5)	2	163 (-3.5)	1
TM5	187-219	206 (4.4), 188 (3.1)	2	187 (-4.5), 196 (-3.7), 219 (-3.3), 190 (-3.2)	4
TM6	381-412	400 (4.4), 412 (3.1)	2	403 (-5.3), 381 (-5.2), 388 (-4.0), 404 (-3.7), 396 (-3.5), 395 (-3.1)	6
TM7	422-443	440 (5.0), 432 (4.4), 441 (3.9), 430 (3.5)	4	426 (-5.3), 422 (-4.6), 443 (-4.0)	3
Intracellular / Extracellular loops & H8
ICL1	-	-	0	-	0
ICL2	131-135	135 (7.9), 131 (3.3)	2	132 (-6.1)	1
ICL3	244-345	272 (10.0), 273 (10.0), 316 (9.2), 317 (9.2), 257 (8.7), 258 (8.7), 261 (8.7), 262 (8.7), 267 (7.9), 268 (7.9), 244 (7.5), 245 (7.5), 318 (5.6), 319 (5.6), 309 (4.4), 310 (4.4), 259 (4.2), 256 (3.2), 334 (3.0), 335 (3.0)	20	280 (-6.1), 276 (-5.2), 250 (-4.4), 253 (-4.4), 278 (-4.1), 344 (-3.5), 345 (-3.5), 304 (-3.3)	8
ECL1	-	-	0	-	0
ECL2	168-181	169 (6.1)	1	181 (-4.5), 168 (-3.5), 170 (-3.3), 179 (-3.3)	4
ECL3	417-417	-	0	417 (-4.6)	1
H8	447-448	447 (3.9)	1	448 (-3.1)	1

Interactive visualizations

ΔRRCS distribution

Active vs inactive comparison

Residue-wise changes

TM domain breakdown

Variants of interest

70 variants mapped to contact positions, sorted by |ΔRRCS| impact.

Position	Protein change	DNA change	Allele freq	Het / Hom	ΔRRCS	AM score	Pathogenicity	Conservation	dbSNP
273	p.Asn273Asp	c.817A>G	6.58e-06	1 / 0	9.95	0.079	BENIGN	0.48	rs1805129793
272	p.Glu272Asp	c.816A>C	6.84e-07	1 / 0	9.95	0.065	BENIGN	0.44
317	p.Asp317Gly	c.950A>G	6.84e-07	1 / 0	9.19	0.060	BENIGN	0.37
257	p.His257Gln	c.771C>A	6.84e-07	1 / 0	8.65	0.067	BENIGN	0.38
258	p.Asn258Ser	c.773A>G	1.24e-03	1799 / 4	8.65	0.058	BENIGN	0.41	rs142006633
258	p.Asn258Lys	c.774C>A	4.79e-06	7 / 0	8.65	-	nan	-	rs762789853
262	p.Asn262Ser	c.785A>G	6.84e-07	1 / 0	8.65	0.199	BENIGN	0.48	rs763856121
261	p.Gln261Glu	c.781C>G	6.16e-06	9 / 0	8.65	0.089	BENIGN	0.45
261	p.Gln261Arg	c.782A>G	6.84e-07	1 / 0	8.65	-	nan	-
268	p.Asp268His	c.802G>C	6.84e-07	1 / 0	7.93	0.148	BENIGN	0.39
267	p.Arg267Ser	c.801G>C	6.84e-07	1 / 0	7.93	0.119	BENIGN	0.39	rs1485924904
135	p.Arg135Trp	c.403C>T	1.37e-06	2 / 0	7.87	0.995	PATHOGENIC	0.93	rs748172206
135	p.Arg135Gln	c.404G>A	3.42e-06	5 / 0	7.87	-	nan	-	rs1446523872
244	p.Asn244Lys	c.732C>A	6.84e-07	1 / 0	7.47	0.256	BENIGN	0.47
245	p.Asn245Ser	c.734A>G	1.37e-06	2 / 0	7.47	0.112	BENIGN	0.50	rs1805121569
245	p.Asn245Lys	c.735T>A	6.84e-07	1 / 0	7.47	-	nan	-
121	p.Arg121Ser	c.363G>T	6.84e-07	1 / 0	6.80	1.000	PATHOGENIC	0.98	rs751591780
318	p.Glu318Lys	c.952G>A	6.16e-06	9 / 0	5.65	0.083	BENIGN	0.42	rs1409906654
426	p.Tyr426Ser	c.1277A>C	6.58e-06	1 / 0	5.26	0.977	PATHOGENIC	1.00	rs1256583527
381	p.Arg381Trp	c.1141C>T	1.37e-06	2 / 0	5.24	0.958	PATHOGENIC	0.73
276	p.Gln276Arg	c.827A>G	6.58e-06	1 / 0	5.24	0.081	BENIGN	0.42	rs1462512567
276	p.Gln276His	c.828G>C	2.74e-06	4 / 0	5.24	-	nan	-	rs1196046513
381	p.Arg381Gln	c.1142G>A	4.79e-06	7 / 0	5.24	-	nan	-	rs1432230108
417	p.Ile417Val	c.1249A>G	6.85e-07	1 / 0	4.56	0.097	BENIGN	0.80	rs1805173244
400	p.Trp400Ser	c.1199G>C	6.59e-06	1 / 0	4.43	0.995	PATHOGENIC	0.97	rs1805169525
309	p.Ser309Thr	c.925T>A	6.84e-07	1 / 0	4.41	0.060	BENIGN	0.44	rs1805140043
310	p.Thr310Ala	c.928A>G	6.58e-06	1 / 0	4.41	0.059	BENIGN	0.48	rs950002962
309	p.Ser309Pro	c.925T>C	1.37e-06	2 / 0	4.41	-	nan	-
309	p.Ser309Tyr	c.926C>A	1.37e-06	2 / 0	4.41	-	nan	-
309	p.Ser309Phe	c.926C>T	6.84e-07	1 / 0	4.41	-	nan	-
310	p.Thr310Asn	c.929C>A	6.84e-07	1 / 0	4.41	-	nan	-
250	p.Ser250Asn	c.749G>A	6.58e-06	1 / 0	4.35	0.076	BENIGN	0.48	rs2131133532
253	p.Asp253Asn	c.757G>A	5.54e-05	81 / 0	4.35	0.069	BENIGN	0.47	rs140681489
250	p.Ser250Arg	c.750C>A	6.84e-07	1 / 0	4.35	-	nan	-	rs964339453
253	p.Asp253Gly	c.758A>G	2.05e-06	3 / 0	4.35	-	nan	-
253	p.Asp253Glu	c.759T>A	1.37e-06	2 / 0	4.35	-	nan	-	rs1805124961
104	p.Tyr104Asp	c.310T>G	6.84e-07	1 / 0	4.27	0.996	PATHOGENIC	0.96
278	p.Glu278Val	c.833A>T	1.37e-06	2 / 0	4.05	0.126	BENIGN	0.46
447	p.Phe447Leu	c.1339T>C	6.84e-07	1 / 0	3.94	1.000	PATHOGENIC	1.00	rs1454431431
80	p.Tyr80Phe	c.239A>T	6.84e-07	1 / 0	3.72	0.259	BENIGN	0.78	rs776183369
404	p.Asn404Ile	c.1211A>T	6.59e-06	1 / 0	3.66	0.986	PATHOGENIC	0.81	rs1805170229
404	p.Asn404Ser	c.1211A>G	6.85e-07	1 / 0	3.66	-	nan	-
430	p.Tyr430Ser	c.1289A>C	6.85e-07	1 / 0	3.54	0.992	PATHOGENIC	1.00
344	p.Val344Met	c.1030G>A	1.78e-05	26 / 0	3.53	0.117	BENIGN	0.44	rs201165506
345	p.Glu345Asp	c.1035G>T	6.84e-07	1 / 0	3.53	0.115	BENIGN	0.48
344	p.Val344Gly	c.1031T>G	1.30e-05	19 / 0	3.53	-	nan	-	rs139037603
344	p.Val344Ala	c.1031T>C	2.12e-05	31 / 0	3.53	-	nan	-	rs139037603
345	p.Glu345Asp	c.1035G>C	6.84e-07	1 / 0	3.53	-	nan	-
163	p.Gln163His	c.489G>T	6.84e-07	1 / 0	3.50	0.972	PATHOGENIC	0.64
168	p.Val168Met	c.502G>A	6.84e-07	1 / 0	3.50	0.118	BENIGN	0.43
163	p.Gln163His	c.489G>C	6.84e-07	1 / 0	3.50	-	nan	-
155	p.Trp155Cys	c.465G>C	6.84e-07	1 / 0	3.45	0.999	PATHOGENIC	0.94
154	p.Leu154Val	c.460C>G	1.37e-06	2 / 0	3.45	0.818	PATHOGENIC	0.94	rs770334609
179	p.Gln179Pro	c.536A>C	3.42e-06	5 / 0	3.34	0.765	PATHOGENIC	0.85	rs1188211079
170	p.Thr170Pro	c.508A>C	6.58e-06	1 / 0	3.34	0.569	PATHOGENIC	0.69	rs764518888
170	p.Thr170Ile	c.509C>T	6.84e-07	1 / 0	3.34	-	nan	-
179	p.Gln179His	c.537G>T	1.37e-06	2 / 0	3.34	-	nan	-
103	p.Asp103His	c.307G>C	6.84e-07	1 / 0	3.28	1.000	PATHOGENIC	0.99
219	p.Lys219Thr	c.656A>C	6.84e-07	1 / 0	3.27	0.211	BENIGN	0.57
304	p.Asp304Val	c.911A>T	4.86e-05	71 / 0	3.27	0.089	BENIGN	0.45	rs778284565
304	p.Asp304Glu	c.912T>A	2.05e-06	3 / 0	3.27	-	nan	-
256	p.Glu256Gln	c.766G>C	6.84e-07	1 / 0	3.21	0.074	BENIGN	0.43
256	p.Glu256Lys	c.766G>A	6.84e-07	1 / 0	3.21	-	nan	-
190	p.Thr190Ala	c.568A>G	6.84e-07	1 / 0	3.20	0.980	PATHOGENIC	0.93
190	p.Thr190Met	c.569C>T	2.05e-06	3 / 0	3.20	-	nan	-	rs1394629702
412	p.Phe412Leu	c.1234T>C	6.85e-07	1 / 0	3.11	0.975	PATHOGENIC	0.70
412	p.Phe412Ser	c.1235T>C	6.85e-07	1 / 0	3.11	-	nan	-
448	p.Lys448Arg	c.1343A>G	4.52e-05	66 / 0	3.11	0.113	BENIGN	0.77	rs1375588764
395	p.Ala395Val	c.1184C>T	1.37e-06	2 / 0	3.11	0.649	PATHOGENIC	0.86
335	p.Asp335Tyr	c.1003G>T	6.84e-07	1 / 0	3.03	0.128	BENIGN	0.55

Complete RRCS results

Res1	AA1	Res2	AA2	Active RRCS	Inactive RRCS	ΔRRCS	\|ΔRRCS\|
272	GLU	273	ASN	9.954	0.000	9.954	9.954
316	LYS	317	ASP	9.185	0.000	9.185	9.185
257	HIS	258	ASN	8.654	0.000	8.654	8.654
261	GLN	262	ASN	8.725	0.073	8.652	8.652
267	ARG	268	ASP	7.928	0.000	7.928	7.928
58	ASN	135	ARG	8.851	0.982	7.870	7.870
244	ASN	245	ASN	7.474	0.000	7.474	7.474
58	ASN	121	ARG	0.000	6.796	-6.796	6.796
132	PRO	280	LYS	0.000	6.114	-6.114	6.114
97	ASP	169	ARG	7.168	1.110	6.058	6.058
318	GLU	319	ASN	5.647	0.000	5.647	5.647
120	ASP	121	ARG	0.000	5.420	-5.420	5.420
403	TYR	426	TYR	2.853	8.109	-5.256	5.256
276	GLN	381	ARG	0.000	5.238	-5.238	5.238
121	ARG	440	TYR	5.022	0.000	5.022	5.022
417	ILE	422	TRP	1.104	5.665	-4.561	4.561
181	PHE	187	THR	3.578	8.037	-4.460	4.460
400	TRP	432	ASN	7.094	2.663	4.432	4.432
121	ARG	206	TYR	4.431	0.000	4.431	4.431
309	SER	310	THR	4.413	0.000	4.413	4.413
250	SER	253	ASP	0.000	4.353	-4.353	4.353
104	TYR	426	TYR	4.377	0.105	4.271	4.271
258	ASN	259	LYS	4.216	0.000	4.216	4.216
114	LEU	440	TYR	4.079	0.000	4.079	4.079
262	ASN	278	GLU	0.000	4.053	-4.053	4.053
388	THR	443	CYS	0.838	4.811	-3.973	3.973
441	ALA	447	PHE	4.300	0.360	3.940	3.940
272	GLU	381	ARG	0.000	3.765	-3.765	3.765
80	TYR	426	TYR	11.187	7.469	3.718	3.718
196	TYR	404	ASN	1.709	5.373	-3.663	3.663
104	TYR	403	TYR	4.221	0.598	3.622	3.622
426	TYR	430	TYR	3.808	0.264	3.544	3.544
344	VAL	345	GLU	0.000	3.527	-3.527	3.527
396	PHE	400	TRP	4.371	7.893	-3.522	3.522
163	GLN	168	VAL	1.361	4.863	-3.502	3.502
154	LEU	155	TRP	3.840	0.389	3.451	3.451
58	ASN	120	ASP	4.255	0.851	3.404	3.404
170	THR	179	GLN	3.713	7.054	-3.341	3.341
118	SER	206	TYR	5.045	1.706	3.338	3.338
131	TYR	135	ARG	3.297	0.000	3.297	3.297
103	ASP	426	TYR	3.279	0.000	3.279	3.279
219	LYS	304	ASP	0.000	3.269	-3.269	3.269
256	GLU	257	HIS	3.213	0.000	3.213	3.213
181	PHE	190	THR	0.000	3.198	-3.198	3.198
188	PHE	412	PHE	3.112	0.000	3.112	3.112
441	ALA	448	LYS	0.000	3.112	-3.112	3.112
395	ALA	432	ASN	0.168	3.276	-3.109	3.109
334	SER	335	ASP	3.028	0.000	3.028	3.028
273	ASN	381	ARG	0.000	3.024	-3.024	3.024
188	PHE	192	ILE	0.071	3.022	-2.951	2.951
168	VAL	179	GLN	0.100	3.026	-2.926	2.926
403	TYR	407	VAL	3.818	0.905	2.913	2.913
8	SER	9	ASN	0.000	2.909	-2.909	2.909
163	GLN	169	ARG	2.148	5.034	-2.886	2.886
260	ILE	261	GLN	2.873	0.000	2.873	2.873
406	MET	422	TRP	3.974	6.832	-2.858	2.858
270	VAL	271	THR	2.849	0.000	2.849	2.849
279	GLU	280	LYS	2.824	0.000	2.824	2.824
180	PHE	181	PHE	1.577	4.374	-2.798	2.798
217	ILE	382	GLU	2.748	0.000	2.748	2.748
69	ASP	110	SER	2.773	0.029	2.744	2.744
76	SER	430	TYR	7.178	4.473	2.704	2.704
214	LYS	382	GLU	2.645	0.000	2.645	2.645
169	ARG	171	VAL	0.773	3.416	-2.644	2.644
437	PRO	442	LEU	2.633	0.000	2.633	2.633
171	VAL	177	TYR	8.820	6.279	2.542	2.542
206	TYR	393	LEU	2.024	4.543	-2.519	2.519
108	ASN	194	ALA	2.602	0.087	2.515	2.515
53	HIS	273	ASN	0.000	2.497	-2.497	2.497
120	ASP	135	ARG	4.197	1.703	2.494	2.494
44	VAL	440	TYR	0.000	2.493	-2.493	2.493
392	ILE	439	CYS	2.456	0.008	2.448	2.448
163	GLN	179	GLN	5.431	2.984	2.447	2.447
399	THR	428	LEU	8.609	6.172	2.437	2.437
180	PHE	187	THR	2.436	0.000	2.436	2.436
452	LYS	456	MET	0.929	3.360	-2.431	2.431
99	TRP	100	LEU	2.807	0.384	2.423	2.423
266	PRO	267	ARG	2.420	0.000	2.420	2.420
117	ILE	389	ILE	0.000	2.419	-2.419	2.419
43	LEU	451	PHE	5.669	3.269	2.400	2.400
121	ARG	135	ARG	0.000	2.385	-2.385	2.385
310	THR	311	SER	2.377	0.000	2.377	2.377
65	LEU	113	ASN	2.436	0.068	2.367	2.367
255	LEU	266	PRO	0.000	2.330	-2.330	2.330
403	TYR	422	TRP	0.694	2.985	-2.292	2.292
117	ILE	121	ARG	2.359	0.098	2.262	2.262
306	ASN	307	THR	2.228	0.000	2.228	2.228
162	TRP	179	GLN	5.218	2.995	2.223	2.223
56	THR	273	ASN	0.000	2.194	-2.194	2.194
121	ARG	124	CYS	0.000	2.187	-2.187	2.187
115	LEU	198	PRO	0.851	3.010	-2.158	2.158
440	TYR	447	PHE	0.000	2.147	-2.147	2.147
245	ASN	246	ASN	2.123	0.000	2.123	2.123
58	ASN	385	VAL	0.000	2.116	-2.116	2.116
162	TRP	183	ASN	2.112	0.000	2.112	2.112
93	PRO	169	ARG	7.713	5.608	2.105	2.105
52	ARG	271	THR	0.000	2.099	-2.099	2.099
301	ILE	305	GLU	0.000	2.086	-2.086	2.086
396	PHE	432	ASN	1.967	4.052	-2.085	2.085
65	LEU	114	LEU	2.468	0.405	2.063	2.063
61	PHE	120	ASP	2.999	0.943	2.056	2.056
337	CYS	338	THR	2.023	0.000	2.023	2.023
30	ALA	427	TRP	3.478	1.473	2.006	2.006
307	THR	308	VAL	1.978	0.000	1.978	1.978
331	THR	332	PRO	3.757	1.798	1.959	1.959
187	THR	411	THR	1.949	0.000	1.949	1.949
121	ARG	389	ILE	0.000	1.941	-1.941	1.941
53	HIS	271	THR	0.000	1.907	-1.907	1.907
62	LEU	440	TYR	1.094	2.953	-1.859	1.859
195	PHE	401	ALA	3.491	1.633	1.858	1.858
181	PHE	411	THR	1.850	0.000	1.850	1.850
33	LEU	434	THR	0.711	2.561	-1.850	1.850
196	TYR	408	LEU	2.318	0.470	1.847	1.847
195	PHE	396	PHE	0.359	2.192	-1.832	1.832
330	LYS	331	THR	0.000	1.784	-1.784	1.784
99	TRP	426	TYR	1.755	0.000	1.755	1.755
398	ILE	428	LEU	1.751	0.000	1.751	1.751
68	ALA	106	VAL	3.462	1.711	1.751	1.751
121	ARG	385	VAL	0.000	1.750	-1.750	1.750
432	ASN	436	ASN	3.834	2.085	1.749	1.749
115	LEU	119	PHE	1.768	0.072	1.695	1.695
2	ASN	3	ASN	1.689	0.000	1.689	1.689
133	VAL	280	LYS	0.000	1.681	-1.681	1.681
122	TYR	205	LEU	4.380	2.730	1.650	1.650
65	LEU	440	TYR	0.272	1.887	-1.614	1.614
442	LEU	451	PHE	1.603	0.000	1.603	1.603
213	SER	385	VAL	1.595	0.000	1.595	1.595
155	TRP	190	THR	3.349	1.774	1.576	1.576
268	ASP	269	PRO	2.142	0.577	1.566	1.566
77	MET	430	TYR	5.742	4.180	1.562	1.562
181	PHE	403	TYR	1.557	0.000	1.557	1.557
127	LYS	130	THR	0.029	1.578	-1.548	1.548
195	PHE	404	ASN	10.351	11.899	-1.548	1.548
247	ASN	248	MET	1.523	0.000	1.523	1.523
181	PHE	422	TRP	1.515	0.000	1.515	1.515
133	VAL	283	SER	0.000	1.515	-1.515	1.515
326	ARG	327	ILE	2.107	0.607	1.500	1.500
406	MET	421	VAL	2.495	3.995	-1.500	1.500
114	LEU	396	PHE	1.479	2.961	-1.483	1.483
75	PHE	102	LEU	0.398	1.874	-1.475	1.475
104	TYR	155	TRP	6.889	8.361	-1.472	1.472
54	LEU	447	PHE	5.748	4.284	1.464	1.464
259	LYS	264	LYS	0.000	1.460	-1.460	1.460
33	LEU	77	MET	2.011	0.555	1.457	1.457
202	MET	396	PHE	1.885	0.432	1.453	1.453
236	VAL	237	GLN	0.000	1.451	-1.451	1.451
80	TYR	84	THR	1.412	2.854	-1.441	1.441
65	LEU	69	ASP	2.218	0.781	1.437	1.437
105	VAL	151	SER	4.740	3.326	1.414	1.414
97	ASP	179	GLN	1.411	0.000	1.411	1.411
250	SER	251	SER	1.406	0.000	1.406	1.406
195	PHE	199	VAL	3.193	1.792	1.401	1.401
188	PHE	411	THR	1.515	2.900	-1.385	1.385
311	SER	371	GLN	0.000	1.384	-1.384	1.384
40	GLY	437	PRO	2.214	3.597	-1.383	1.383
399	THR	432	ASN	5.166	6.549	-1.382	1.382
203	THR	393	LEU	1.374	0.000	1.374	1.374
34	SER	73	GLY	1.727	3.094	-1.367	1.367
60	TYR	137	THR	0.150	1.507	-1.356	1.356
270	VAL	275	VAL	0.000	1.329	-1.329	1.329
79	LEU	99	TRP	3.550	4.878	-1.328	1.328
65	LEU	436	ASN	2.395	1.070	1.326	1.326
104	TYR	178	ILE	6.076	4.754	1.322	1.322
411	THR	412	PHE	1.805	0.495	1.310	1.310
163	GLN	164	PHE	1.575	2.870	-1.295	1.295
271	THR	274	CYS	0.000	1.294	-1.294	1.294
52	ARG	274	CYS	0.000	1.287	-1.287	1.287
114	LEU	436	ASN	1.284	0.000	1.284	1.284
298	ASP	301	ILE	0.000	1.280	-1.280	1.280
155	TRP	180	PHE	1.296	0.022	1.274	1.274
178	ILE	181	PHE	6.225	4.954	1.271	1.271
315	SER	316	LYS	1.261	0.000	1.261	1.261
206	TYR	389	ILE	3.255	4.504	-1.249	1.249
45	MET	63	PHE	5.043	6.283	-1.240	1.240
72	ILE	103	ASP	0.145	1.382	-1.238	1.238
127	LYS	132	PRO	0.585	1.822	-1.237	1.237
89	TRP	173	ASP	0.000	1.236	-1.236	1.236
188	PHE	407	VAL	0.000	1.232	-1.232	1.232
387	ARG	443	CYS	0.000	1.214	-1.214	1.214
195	PHE	196	TYR	2.849	1.642	1.207	1.207
184	ALA	411	THR	2.114	0.908	1.206	1.206
71	ILE	102	LEU	0.686	1.888	-1.202	1.202
181	PHE	407	VAL	1.193	0.000	1.193	1.193
255	LEU	256	GLU	1.179	0.000	1.179	1.179
69	ASP	436	ASN	5.530	4.368	1.162	1.162
150	LEU	154	LEU	0.000	1.152	-1.152	1.152
80	TYR	83	TYR	1.170	0.033	1.137	1.137
112	MET	147	ALA	2.149	1.019	1.130	1.130
271	THR	272	GLU	1.129	0.000	1.129	1.129
105	VAL	152	PHE	3.763	2.634	1.128	1.128
155	TRP	181	PHE	0.000	1.118	-1.118	1.118
16	SER	18	TYR	0.577	1.689	-1.112	1.112
439	CYS	440	TYR	1.110	0.000	1.110	1.110
4	SER	5	THR	0.000	1.106	-1.106	1.106
441	ALA	451	PHE	0.000	1.105	-1.105	1.105
108	ASN	154	LEU	1.118	0.017	1.101	1.101
115	LEU	202	MET	1.572	2.650	-1.077	1.077
162	TRP	180	PHE	9.118	8.050	1.068	1.068
183	ASN	186	VAL	2.835	1.771	1.064	1.064
181	PHE	410	ASN	1.045	0.000	1.045	1.045
399	THR	429	CYS	3.461	2.418	1.043	1.043
122	TYR	123	PHE	3.090	2.055	1.034	1.034
117	ILE	440	TYR	1.022	0.000	1.022	1.022
123	PHE	131	TYR	10.098	11.119	-1.021	1.021
114	LEU	393	LEU	0.000	1.020	-1.020	1.020
84	THR	423	THR	1.390	0.374	1.016	1.016
72	ILE	107	SER	1.359	0.344	1.015	1.015
134	LYS	139	MET	0.328	1.337	-1.009	1.009
210	SER	389	ILE	1.007	0.000	1.007	1.007
37	THR	434	THR	7.028	6.056	0.971	0.971
69	ASP	433	SER	11.663	12.632	-0.969	0.969
89	TRP	174	GLY	3.502	4.468	-0.967	0.967
100	LEU	177	TYR	2.015	2.977	-0.962	0.962
121	ARG	392	ILE	0.958	0.000	0.958	0.958
180	PHE	186	VAL	1.370	2.326	-0.955	0.955
80	TYR	423	THR	5.197	4.242	0.955	0.955
73	GLY	78	ASN	2.448	1.497	0.951	0.951
155	TRP	194	ALA	1.374	0.424	0.950	0.950
97	ASP	163	GLN	3.043	2.094	0.949	0.949
160	LEU	161	PHE	0.140	1.085	-0.945	0.945
108	ASN	151	SER	7.662	6.717	0.945	0.945
46	VAL	454	LEU	0.319	1.259	-0.940	0.940
391	ALA	439	CYS	0.274	1.210	-0.936	0.936
399	THR	431	ILE	0.935	0.000	0.935	0.935
89	TRP	91	LEU	1.917	2.849	-0.933	0.933
302	THR	305	GLU	0.000	0.932	-0.932	0.932
27	VAL	85	VAL	1.247	0.320	0.927	0.927
84	THR	427	TRP	0.926	0.000	0.926	0.926
406	MET	425	GLY	1.110	0.184	0.926	0.926
33	LEU	427	TRP	0.000	0.923	-0.923	0.923
169	ARG	179	GLN	3.137	2.220	0.917	0.917
82	LEU	91	LEU	0.190	1.106	-0.917	0.917
57	VAL	136	THR	0.378	1.293	-0.915	0.915
120	ASP	131	TYR	5.425	6.336	-0.910	0.910
197	LEU	201	ILE	1.453	0.551	0.903	0.903
116	ILE	143	MET	2.646	3.547	-0.901	0.901
23	VAL	85	VAL	0.573	1.473	-0.901	0.901
259	LYS	260	ILE	0.895	0.000	0.895	0.895
55	GLN	60	TYR	1.145	0.254	0.891	0.891
333	LYS	334	SER	1.323	0.432	0.891	0.891
80	TYR	99	TRP	2.574	3.453	-0.879	0.879
390	LEU	394	LEU	2.061	1.192	0.869	0.869
64	SER	113	ASN	6.033	5.169	0.864	0.864
270	VAL	274	CYS	0.000	0.858	-0.858	0.858
108	ASN	155	TRP	5.095	5.943	-0.848	0.848
114	LEU	392	ILE	0.000	0.848	-0.848	0.848
191	ALA	404	ASN	0.149	0.991	-0.842	0.842
38	ILE	73	GLY	2.821	1.983	0.838	0.838
72	ILE	76	SER	1.205	2.025	-0.820	0.820
33	LEU	431	ILE	0.000	0.806	-0.806	0.806
62	LEU	392	ILE	0.000	0.806	-0.806	0.806
101	ALA	160	LEU	1.562	0.757	0.805	0.805
437	PRO	451	PHE	0.000	0.801	-0.801	0.801
162	TRP	186	VAL	0.798	0.000	0.798	0.798
408	LEU	412	PHE	0.000	0.789	-0.789	0.789
191	ALA	196	TYR	3.870	4.651	-0.781	0.781
243	PRO	244	ASN	0.780	0.000	0.780	0.780
114	LEU	202	MET	1.727	2.506	-0.779	0.779
72	ILE	77	MET	4.595	3.829	0.766	0.766
80	TYR	427	TRP	4.100	3.334	0.766	0.766
110	SER	436	ASN	0.760	0.000	0.760	0.760
216	ARG	382	GLU	0.000	0.758	-0.758	0.758
403	TYR	429	CYS	2.034	1.281	0.753	0.753
99	TRP	103	ASP	1.198	0.451	0.748	0.748
335	ASP	336	SER	0.744	0.000	0.744	0.744
26	ILE	85	VAL	0.085	0.821	-0.737	0.737
403	TYR	425	GLY	1.346	2.077	-0.730	0.730
391	ALA	443	CYS	0.000	0.725	-0.725	0.725
61	PHE	140	ALA	2.977	2.257	0.720	0.720
319	ASN	320	SER	0.720	0.000	0.720	0.720
206	TYR	209	ILE	0.751	0.032	0.719	0.719
48	ILE	59	ASN	0.946	1.662	-0.717	0.717
83	TYR	175	GLU	1.417	0.702	0.715	0.715
100	LEU	104	TYR	0.715	0.000	0.715	0.715
89	TRP	176	CYS	3.836	3.123	0.713	0.713
417	ILE	421	VAL	0.053	0.760	-0.707	0.707
424	ILE	428	LEU	0.000	0.706	-0.706	0.706
48	ILE	55	GLN	3.342	2.645	0.697	0.697
89	TRP	175	GLU	0.312	0.991	-0.679	0.679
57	VAL	61	PHE	0.000	0.673	-0.673	0.673
76	SER	103	ASP	5.829	5.159	0.670	0.670
106	VAL	148	TRP	0.368	1.030	-0.663	0.663
112	MET	193	ALA	0.662	0.000	0.662	0.662
47	SER	454	LEU	1.393	2.050	-0.656	0.656
65	LEU	117	ILE	0.656	0.000	0.656	0.656
184	ALA	410	ASN	0.000	0.653	-0.653	0.653
120	ASP	124	CYS	0.252	0.896	-0.644	0.644
209	ILE	389	ILE	0.643	0.000	0.643	0.643
34	SER	77	MET	2.275	1.633	0.642	0.642
83	TYR	176	CYS	3.043	2.404	0.639	0.639
99	TRP	176	CYS	1.473	2.099	-0.625	0.625
64	SER	148	TRP	3.074	3.699	-0.625	0.625
112	MET	198	PRO	0.625	0.000	0.625	0.625
104	TYR	181	PHE	2.168	2.790	-0.622	0.622
43	LEU	454	LEU	0.154	0.776	-0.622	0.622
442	LEU	448	LYS	0.620	0.000	0.620	0.620
388	THR	444	ASN	0.000	0.619	-0.619	0.619
41	ASN	437	PRO	3.842	4.461	-0.619	0.619
283	SER	284	ASN	0.615	0.000	0.615	0.615
72	ILE	106	VAL	2.134	1.520	0.614	0.614
207	TRP	208	HIS	3.662	4.274	-0.612	0.612
206	TYR	440	TYR	0.603	0.000	0.603	0.603
158	ALA	180	PHE	3.241	2.640	0.601	0.601
248	MET	249	PRO	1.624	1.030	0.594	0.594
187	THR	407	VAL	1.092	1.686	-0.594	0.594
96	CYS	169	ARG	0.628	0.036	0.592	0.592
301	ILE	306	ASN	0.000	0.590	-0.590	0.590
76	SER	99	TRP	2.142	2.725	-0.583	0.583
217	ILE	221	LYS	1.170	0.588	0.583	0.583
364	LYS	368	MET	0.200	0.782	-0.582	0.582
119	PHE	201	ILE	1.398	0.826	0.572	0.572
44	VAL	441	ALA	0.571	0.000	0.571	0.571
65	LEU	392	ILE	0.000	0.562	-0.562	0.562
361	VAL	365	ILE	0.442	1.004	-0.562	0.562
124	CYS	135	ARG	0.241	0.802	-0.561	0.561
444	ASN	447	PHE	2.538	3.097	-0.559	0.559
58	ASN	124	CYS	0.559	0.000	0.559	0.559
438	ALA	443	CYS	0.558	0.000	0.558	0.558
392	ILE	436	ASN	0.000	0.555	-0.555	0.555
317	ASP	318	GLU	0.555	0.000	0.555	0.555
24	VAL	28	LEU	0.000	0.552	-0.552	0.552
242	LYS	243	PRO	0.371	0.922	-0.550	0.550
338	THR	339	PRO	1.113	0.568	0.545	0.545
251	SER	252	ASP	0.000	0.544	-0.544	0.544
102	LEU	106	VAL	0.943	0.400	0.543	0.543
407	VAL	422	TRP	1.862	2.399	-0.537	0.537
413	CYS	416	CYS	3.096	3.631	-0.535	0.535
96	CYS	176	CYS	6.248	6.783	-0.534	0.534
406	MET	417	ILE	3.295	3.829	-0.534	0.534
47	SER	450	THR	2.913	3.439	-0.526	0.526
413	CYS	415	PRO	0.000	0.521	-0.521	0.521
100	LEU	176	CYS	1.158	1.679	-0.521	0.521
79	LEU	89	TRP	0.926	1.443	-0.517	0.517
371	GLN	372	PRO	0.149	0.666	-0.517	0.517
45	MET	66	ALA	1.061	0.546	0.515	0.515
99	TRP	430	TYR	0.924	0.412	0.513	0.513
113	ASN	148	TRP	1.134	0.621	0.513	0.513
29	VAL	33	LEU	0.511	0.000	0.511	0.511
118	SER	202	MET	2.072	2.579	-0.507	0.507
41	ASN	66	ALA	5.454	4.949	0.505	0.505
77	MET	434	THR	0.255	0.759	-0.504	0.504
57	VAL	135	ARG	4.787	4.287	0.500	0.500
82	LEU	90	PRO	0.030	0.529	-0.499	0.499
392	ILE	440	TYR	2.647	2.150	0.497	0.497
453	HIS	457	CYS	2.649	3.143	-0.495	0.495
124	CYS	131	TYR	2.354	2.844	-0.490	0.490
229	ASP	230	PRO	0.682	1.169	-0.487	0.487
25	PHE	29	VAL	1.641	2.127	-0.486	0.486
410	ASN	422	TRP	1.293	1.772	-0.479	0.479
130	THR	134	LYS	0.478	0.000	0.478	0.478
458	HIS	462	ILE	0.000	0.475	-0.475	0.475
275	VAL	279	GLU	0.000	0.474	-0.474	0.474
62	LEU	117	ILE	0.672	0.198	0.474	0.474
83	TYR	89	TRP	5.213	4.739	0.474	0.474
105	VAL	156	ALA	1.543	1.072	0.471	0.471
355	ASP	356	GLU	0.461	0.000	0.461	0.461
139	MET	143	MET	0.077	0.538	-0.461	0.461
191	ALA	407	VAL	0.000	0.451	-0.451	0.451
77	MET	431	ILE	0.000	0.446	-0.446	0.446
199	VAL	202	MET	0.000	0.442	-0.442	0.442
161	PHE	164	PHE	0.552	0.993	-0.441	0.441
89	TRP	99	TRP	6.511	6.074	0.437	0.437
54	LEU	59	ASN	5.872	6.308	-0.435	0.435
206	TYR	390	LEU	0.000	0.435	-0.435	0.435
144	ILE	148	TRP	0.569	1.003	-0.434	0.434
388	THR	440	TYR	0.000	0.434	-0.434	0.434
112	MET	194	ALA	0.434	0.000	0.434	0.434
61	PHE	117	ILE	2.044	2.477	-0.433	0.433
113	ASN	144	ILE	0.101	0.534	-0.433	0.433
349	SER	350	SER	0.000	0.429	-0.429	0.429
103	ASP	107	SER	0.806	0.381	0.425	0.425
60	TYR	144	ILE	1.883	2.308	-0.425	0.425
64	SER	144	ILE	2.577	3.002	-0.425	0.425
59	ASN	447	PHE	2.363	1.941	0.421	0.421
377	PRO	382	GLU	0.000	0.417	-0.417	0.417
436	ASN	441	ALA	0.415	0.000	0.415	0.415
52	ARG	268	ASP	0.000	0.415	-0.415	0.415
97	ASP	160	LEU	1.840	2.255	-0.415	0.415
191	ALA	408	LEU	0.415	0.000	0.415	0.415
199	VAL	397	ILE	0.089	0.499	-0.410	0.410
291	ALA	292	VAL	0.410	0.000	0.410	0.410
52	ARG	273	ASN	0.000	0.409	-0.409	0.409
226	ALA	227	ASN	0.000	0.409	-0.409	0.409
74	VAL	75	PHE	3.351	3.756	-0.405	0.405
125	VAL	209	ILE	0.874	0.471	0.403	0.403
44	VAL	62	LEU	0.516	0.114	0.402	0.402
40	GLY	451	PHE	0.399	0.000	0.399	0.399
359	ASN	363	ARG	0.399	0.000	0.399	0.399
28	LEU	32	SER	0.399	0.000	0.399	0.399
114	LEU	432	ASN	0.398	0.000	0.398	0.398
183	ASN	185	ALA	0.770	1.168	-0.398	0.398
100	LEU	178	ILE	1.190	1.582	-0.392	0.392
199	VAL	396	PHE	0.892	0.501	0.391	0.391
103	ASP	430	TYR	6.567	6.178	0.388	0.388
56	THR	59	ASN	3.344	3.732	-0.387	0.387
81	THR	427	TRP	3.225	2.841	0.383	0.383
110	SER	432	ASN	0.382	0.000	0.382	0.382
71	ILE	148	TRP	0.347	0.730	-0.382	0.382
115	LEU	201	ILE	1.210	0.834	0.376	0.376
269	PRO	270	VAL	0.376	0.000	0.376	0.376
271	THR	273	ASN	0.000	0.372	-0.372	0.372
61	PHE	116	ILE	3.021	2.650	0.371	0.371
435	ILE	439	CYS	1.012	0.641	0.371	0.371
37	THR	77	MET	2.082	2.451	-0.370	0.370
409	ILE	417	ILE	1.449	1.818	-0.369	0.369
423	THR	427	TRP	0.637	1.006	-0.368	0.368
89	TRP	90	PRO	0.303	0.666	-0.363	0.363
125	VAL	212	ALA	0.581	0.939	-0.358	0.358
44	VAL	447	PHE	1.082	0.727	0.356	0.356
14	LEU	20	THR	0.355	0.000	0.355	0.355
276	GLN	377	PRO	0.000	0.355	-0.355	0.355
295	ASN	296	MET	0.000	0.352	-0.352	0.352
169	ARG	173	ASP	0.000	0.352	-0.352	0.352
52	ARG	55	GLN	0.906	0.555	0.352	0.352
201	ILE	205	LEU	1.075	0.724	0.351	0.351
221	LYS	382	GLU	0.350	0.000	0.350	0.350
214	LYS	386	THR	0.349	0.000	0.349	0.349
41	ASN	433	SER	1.916	2.257	-0.341	0.341
202	MET	393	LEU	0.565	0.905	-0.340	0.340
88	TYR	90	PRO	1.060	0.721	0.339	0.339
49	LYS	55	GLN	2.320	1.985	0.335	0.335
37	THR	73	GLY	1.044	1.374	-0.331	0.331
68	ALA	148	TRP	3.496	3.167	0.329	0.329
123	PHE	128	PRO	0.443	0.119	0.324	0.324
118	SER	393	LEU	0.000	0.322	-0.322	0.322
101	ALA	159	ILE	2.574	2.895	-0.321	0.321
311	SER	312	LEU	0.318	0.000	0.318	0.318
77	MET	427	TRP	2.670	2.985	-0.315	0.315
378	PRO	380	SER	1.221	0.906	0.315	0.315
250	SER	252	ASP	0.000	0.313	-0.313	0.313
72	ILE	433	SER	2.793	2.481	0.312	0.312
286	SER	287	THR	0.000	0.309	-0.309	0.309
178	ILE	180	PHE	4.906	4.604	0.302	0.302
108	ASN	112	MET	2.088	1.788	0.299	0.299
51	ASN	54	LEU	2.271	1.972	0.299	0.299
444	ASN	446	THR	1.635	1.933	-0.298	0.298
63	PHE	67	CYS	1.779	1.482	0.297	0.297
206	TYR	392	ILE	0.293	0.000	0.293	0.293
388	THR	392	ILE	0.631	0.338	0.293	0.293
258	ASN	262	ASN	0.000	0.292	-0.292	0.292
438	ALA	442	LEU	0.289	0.000	0.289	0.289
71	ILE	76	SER	0.919	0.632	0.287	0.287
48	ILE	447	PHE	2.277	1.990	0.287	0.287
80	TYR	430	TYR	2.245	2.532	-0.287	0.287
417	ILE	418	PRO	0.655	0.370	0.285	0.285
119	PHE	205	LEU	4.691	4.407	0.283	0.283
171	VAL	175	GLU	0.407	0.124	0.282	0.282
38	ILE	70	LEU	2.003	2.285	-0.281	0.281
109	ALA	148	TRP	2.323	2.044	0.279	0.279
159	ILE	178	ILE	1.540	1.819	-0.279	0.279
419	ASN	422	TRP	0.000	0.279	-0.279	0.279
38	ILE	74	VAL	2.157	2.433	-0.276	0.276
297	ARG	298	ASP	0.275	0.000	0.275	0.275
100	LEU	426	TYR	0.273	0.000	0.273	0.273
170	THR	177	TYR	1.918	1.645	0.273	0.273
402	PRO	428	LEU	1.154	0.882	0.272	0.272
128	PRO	216	ARG	1.574	1.302	0.272	0.272
436	ASN	440	TYR	1.868	1.597	0.271	0.271
43	LEU	455	LEU	0.350	0.619	-0.269	0.269
5	THR	6	ASN	0.288	0.557	-0.268	0.268
1	MET	2	ASN	0.267	0.000	0.267	0.267
308	VAL	309	SER	0.265	0.000	0.265	0.265
180	PHE	190	THR	0.265	0.000	0.265	0.265
121	ARG	209	ILE	1.686	1.948	-0.262	0.262
111	VAL	194	ALA	1.297	1.036	0.261	0.261
44	VAL	451	PHE	2.959	2.700	0.258	0.258
168	VAL	170	THR	0.000	0.258	-0.258	0.258
428	LEU	431	ILE	0.257	0.000	0.257	0.257
397	ILE	402	PRO	0.430	0.174	0.256	0.256
394	LEU	398	ILE	0.280	0.025	0.255	0.255
395	ALA	439	CYS	0.497	0.243	0.254	0.254
86	ILE	90	PRO	0.879	0.625	0.253	0.253
41	ASN	69	ASP	4.850	5.103	-0.253	0.253
70	LEU	74	VAL	0.750	0.498	0.252	0.252
111	VAL	198	PRO	1.080	1.332	-0.251	0.251
135	ARG	280	LYS	0.000	0.250	-0.250	0.250
34	SER	38	ILE	0.685	0.931	-0.246	0.246
397	ILE	401	ALA	0.273	0.031	0.242	0.242
59	ASN	62	LEU	0.731	0.974	-0.242	0.242
91	LEU	95	VAL	1.912	1.674	0.237	0.237
154	LEU	190	THR	0.237	0.000	0.237	0.237
61	PHE	113	ASN	0.477	0.240	0.237	0.237
34	SER	78	ASN	4.222	3.990	0.233	0.233
224	PRO	225	VAL	0.232	0.000	0.232	0.232
113	ASN	147	ALA	0.459	0.231	0.228	0.228
175	GLU	177	TYR	2.646	2.873	-0.228	0.228
162	TRP	166	VAL	2.991	2.763	0.227	0.227
195	PHE	400	TRP	3.814	4.039	-0.225	0.225
107	SER	400	TRP	3.075	2.850	0.225	0.225
59	ASN	444	ASN	0.225	0.000	0.225	0.225
410	ASN	414	ALA	1.176	0.954	0.222	0.222
127	LYS	131	TYR	0.278	0.499	-0.221	0.221
202	MET	440	TYR	0.220	0.000	0.220	0.220
44	VAL	437	PRO	0.998	1.217	-0.220	0.220
152	PHE	156	ALA	2.081	2.299	-0.218	0.218
47	SER	54	LEU	2.363	2.581	-0.218	0.218
111	VAL	396	PHE	1.457	1.241	0.217	0.217
16	SER	17	PRO	1.062	1.276	-0.214	0.214
72	ILE	430	TYR	1.885	2.097	-0.213	0.213
112	MET	151	SER	0.852	0.640	0.212	0.212
288	SER	289	VAL	0.000	0.211	-0.211	0.211
82	LEU	86	ILE	1.504	1.714	-0.210	0.210
217	ILE	220	ASP	0.202	0.000	0.202	0.202
131	TYR	139	MET	0.000	0.199	-0.199	0.199
109	ALA	151	SER	4.089	3.892	0.198	0.198
157	PRO	162	TRP	0.181	0.378	-0.197	0.197
122	TYR	208	HIS	1.199	1.395	-0.195	0.195
155	TRP	159	ILE	0.541	0.733	-0.192	0.192
396	PHE	397	ILE	0.000	0.190	-0.190	0.190
45	MET	70	LEU	0.698	0.509	0.190	0.190
175	GLU	419	ASN	0.186	0.000	0.186	0.186
399	THR	435	ILE	0.000	0.184	-0.184	0.184
89	TRP	96	CYS	7.008	6.825	0.183	0.183
384	LYS	388	THR	0.182	0.000	0.182	0.182
265	ALA	266	PRO	0.984	0.806	0.178	0.178
71	ILE	106	VAL	1.740	1.918	-0.178	0.178
278	GLU	279	GLU	0.178	0.000	0.178	0.178
42	ILE	70	LEU	1.059	0.882	0.177	0.177
12	LEU	15	THR	0.177	0.000	0.177	0.177
65	LEU	110	SER	2.543	2.367	0.177	0.177
198	PRO	202	MET	0.000	0.176	-0.176	0.176
207	TRP	211	ARG	1.237	1.064	0.173	0.173
47	SER	447	PHE	0.791	0.618	0.173	0.173
30	ALA	81	THR	1.673	1.844	-0.171	0.171
118	SER	209	ILE	0.321	0.491	-0.170	0.170
75	PHE	99	TRP	0.170	0.000	0.170	0.170
395	ALA	436	ASN	0.000	0.169	-0.169	0.169
384	LYS	443	CYS	0.000	0.168	-0.168	0.168
118	SER	205	LEU	1.472	1.639	-0.167	0.167
51	ASN	53	HIS	2.893	3.059	-0.166	0.166
116	ILE	144	ILE	0.166	0.000	0.166	0.166
234	SER	235	LEU	0.165	0.000	0.165	0.165
90	PRO	91	LEU	0.277	0.442	-0.165	0.165
51	ASN	446	THR	0.784	0.620	0.164	0.164
431	ILE	435	ILE	1.085	1.246	-0.162	0.162
38	ILE	78	ASN	0.160	0.000	0.160	0.160
188	PHE	408	LEU	4.248	4.408	-0.159	0.159
96	CYS	175	GLU	0.105	0.265	-0.159	0.159
410	ASN	417	ILE	1.225	1.383	-0.158	0.158
114	LEU	117	ILE	0.229	0.071	0.158	0.158
52	ARG	264	LYS	0.000	0.157	-0.157	0.157
327	ILE	329	THR	0.156	0.000	0.156	0.156
170	THR	171	VAL	0.152	0.000	0.152	0.152
124	CYS	216	ARG	0.000	0.152	-0.152	0.152
97	ASP	159	ILE	0.751	0.899	-0.148	0.148
62	LEU	447	PHE	0.563	0.416	0.147	0.147
41	ASN	70	LEU	1.728	1.875	-0.147	0.147
111	VAL	400	TRP	0.145	0.000	0.145	0.145
68	ALA	109	ALA	0.142	0.000	0.142	0.142
96	CYS	97	ASP	0.364	0.504	-0.140	0.140
69	ASP	72	ILE	0.140	0.000	0.140	0.140
81	THR	85	VAL	0.342	0.481	-0.139	0.139
47	SER	451	PHE	3.272	3.133	0.139	0.139
105	VAL	155	TRP	1.398	1.266	0.132	0.132
184	ALA	188	PHE	0.131	0.000	0.131	0.131
210	SER	386	THR	0.131	0.000	0.131	0.131
16	SER	19	LYS	0.131	0.000	0.131	0.131
154	LEU	194	ALA	0.131	0.000	0.131	0.131
117	ILE	206	TYR	0.130	0.000	0.130	0.130
418	PRO	421	VAL	1.308	1.438	-0.130	0.130
57	VAL	137	THR	0.634	0.763	-0.129	0.129
159	ILE	180	PHE	1.502	1.374	0.128	0.128
377	PRO	378	PRO	0.388	0.515	-0.128	0.128
125	VAL	216	ARG	2.837	2.963	-0.127	0.127
171	VAL	179	GLN	0.796	0.921	-0.126	0.126
155	TRP	178	ILE	0.201	0.077	0.124	0.124
131	TYR	132	PRO	1.144	1.020	0.123	0.123
213	SER	217	ILE	0.295	0.172	0.122	0.122
427	TRP	430	TYR	0.473	0.351	0.121	0.121
412	PHE	413	CYS	0.119	0.000	0.119	0.119
154	LEU	193	ALA	0.119	0.000	0.119	0.119
399	THR	425	GLY	0.117	0.000	0.117	0.117
258	ASN	263	GLY	0.000	0.117	-0.117	0.117
187	THR	408	LEU	0.116	0.000	0.116	0.116
181	PHE	186	VAL	0.000	0.115	-0.115	0.115
75	PHE	79	LEU	0.002	0.117	-0.115	0.115
202	MET	206	TYR	0.114	0.000	0.114	0.114
172	GLU	175	GLU	0.000	0.112	-0.112	0.112
420	THR	424	ILE	0.198	0.089	0.110	0.110
26	ILE	81	THR	0.000	0.109	-0.109	0.109
210	SER	214	LYS	0.677	0.785	-0.108	0.108
416	CYS	417	ILE	0.000	0.105	-0.105	0.105
320	SER	321	LYS	0.160	0.265	-0.105	0.105
103	ASP	104	TYR	0.226	0.121	0.105	0.105
37	THR	433	SER	1.927	1.825	0.102	0.102
283	SER	286	SER	0.000	0.101	-0.101	0.101
98	LEU	160	LEU	1.314	1.214	0.100	0.100
96	CYS	177	TYR	0.269	0.368	-0.098	0.098
80	TYR	422	TRP	0.449	0.546	-0.098	0.098
190	THR	195	PHE	0.031	0.128	-0.097	0.097
119	PHE	123	PHE	1.390	1.294	0.096	0.096
200	ILE	204	VAL	0.033	0.127	-0.094	0.094
162	TRP	165	ILE	0.143	0.050	0.093	0.093
344	VAL	346	VAL	0.093	0.000	0.093	0.093
19	LYS	22	GLU	0.093	0.000	0.093	0.093
62	LEU	388	THR	0.000	0.090	-0.090	0.090
409	ILE	414	ALA	0.142	0.053	0.089	0.089
399	THR	400	TRP	1.872	1.961	-0.089	0.089
190	THR	194	ALA	0.000	0.088	-0.088	0.088
44	VAL	48	ILE	0.421	0.508	-0.088	0.088
48	ILE	63	PHE	2.390	2.303	0.087	0.087
123	PHE	127	LYS	0.000	0.086	-0.086	0.086
177	TYR	182	SER	0.000	0.085	-0.085	0.085
378	PRO	379	PRO	0.592	0.677	-0.085	0.085
409	ILE	413	CYS	0.084	0.000	0.084	0.084
152	PHE	153	ILE	0.103	0.019	0.084	0.084
188	PHE	196	TYR	0.000	0.083	-0.083	0.083
96	CYS	100	LEU	1.030	0.947	0.083	0.083
258	ASN	261	GLN	0.000	0.082	-0.082	0.082
152	PHE	157	PRO	1.958	1.876	0.081	0.081
69	ASP	440	TYR	0.000	0.081	-0.081	0.081
83	TYR	84	THR	0.000	0.081	-0.081	0.081
285	ASP	288	SER	0.000	0.080	-0.080	0.080
79	LEU	82	LEU	0.090	0.010	0.080	0.080
37	THR	41	ASN	0.609	0.688	-0.079	0.079
110	SER	433	SER	0.078	0.000	0.078	0.078
403	TYR	404	ASN	0.905	0.827	0.077	0.077
106	VAL	107	SER	0.000	0.077	-0.077	0.077
3	ASN	5	THR	0.076	0.000	0.076	0.076
101	ALA	156	ALA	0.474	0.399	0.075	0.075
446	THR	450	THR	0.096	0.171	-0.075	0.075
89	TRP	95	VAL	2.084	2.158	-0.074	0.074
151	SER	156	ALA	0.014	0.088	-0.074	0.074
409	ILE	416	CYS	0.298	0.225	0.073	0.073
149	VAL	153	ILE	0.883	0.955	-0.072	0.072
400	TRP	429	CYS	5.701	5.631	0.070	0.070
45	MET	67	CYS	1.235	1.166	0.069	0.069
71	ILE	75	PHE	0.367	0.436	-0.069	0.069
223	GLU	224	PRO	0.353	0.284	0.069	0.069
227	ASN	229	ASP	0.000	0.068	-0.068	0.068
54	LEU	444	ASN	0.219	0.151	0.068	0.068
79	LEU	91	LEU	0.620	0.687	-0.067	0.067
36	VAL	434	THR	0.874	0.808	0.067	0.067
94	VAL	98	LEU	0.267	0.333	-0.066	0.066
193	ALA	198	PRO	1.867	1.932	-0.065	0.065
51	ASN	450	THR	3.080	3.015	0.065	0.065
9	ASN	10	ASN	0.072	0.008	0.064	0.064
48	ILE	54	LEU	1.418	1.482	-0.064	0.064
55	GLN	273	ASN	0.000	0.064	-0.064	0.064
396	PHE	401	ALA	0.024	0.087	-0.063	0.063
68	ALA	110	SER	1.171	1.110	0.062	0.062
122	TYR	126	THR	3.994	4.055	-0.060	0.060
61	PHE	135	ARG	0.060	0.000	0.060	0.060
84	THR	85	VAL	0.000	0.059	-0.059	0.059
405	VAL	409	ILE	0.525	0.466	0.059	0.059
57	VAL	140	ALA	0.879	0.820	0.059	0.059
26	ILE	31	GLY	0.000	0.059	-0.059	0.059
109	ALA	147	ALA	0.250	0.192	0.059	0.059
67	CYS	148	TRP	0.624	0.681	-0.057	0.057
86	ILE	88	TYR	4.077	4.020	0.057	0.057
389	ILE	393	LEU	0.305	0.361	-0.057	0.057
192	ILE	198	PRO	0.294	0.238	0.056	0.056
314	HIS	315	SER	0.055	0.000	0.055	0.055
139	MET	142	MET	0.002	0.057	-0.055	0.055
346	VAL	347	VAL	0.054	0.000	0.054	0.054
376	LYS	377	PRO	0.481	0.534	-0.053	0.053
395	ALA	435	ILE	0.398	0.345	0.053	0.053
296	MET	297	ARG	0.000	0.052	-0.052	0.052
450	THR	454	LEU	0.412	0.464	-0.051	0.051
171	VAL	176	CYS	0.172	0.122	0.050	0.050
262	ASN	274	CYS	0.000	0.050	-0.050	0.050
379	PRO	383	LYS	0.000	0.049	-0.049	0.049
447	PHE	451	PHE	0.739	0.787	-0.048	0.048
56	THR	58	ASN	0.362	0.411	-0.048	0.048
261	GLN	278	GLU	0.000	0.048	-0.048	0.048
17	PRO	18	TYR	0.184	0.137	0.048	0.048
232	SER	233	PRO	0.571	0.523	0.048	0.048
111	VAL	115	LEU	0.000	0.047	-0.047	0.047
44	VAL	66	ALA	0.954	0.907	0.047	0.047
116	ILE	147	ALA	0.672	0.626	0.047	0.047
109	ALA	113	ASN	0.107	0.154	-0.046	0.046
83	TYR	99	TRP	0.000	0.046	-0.046	0.046
219	LYS	220	ASP	0.045	0.000	0.045	0.045
83	TYR	88	TYR	5.193	5.237	-0.044	0.044
126	THR	127	LYS	0.739	0.695	0.044	0.044
129	LEU	130	THR	0.043	0.000	0.043	0.043
136	THR	138	LYS	0.479	0.522	-0.043	0.043
35	LEU	39	ILE	1.668	1.710	-0.042	0.042
136	THR	139	MET	0.785	0.745	0.040	0.040
196	TYR	405	VAL	1.786	1.825	-0.039	0.039
382	GLU	386	THR	0.039	0.000	0.039	0.039
256	GLU	260	ILE	0.000	0.038	-0.038	0.038
385	VAL	389	ILE	0.743	0.779	-0.035	0.035
123	PHE	126	THR	0.328	0.293	0.035	0.035
88	TYR	174	GLY	3.219	3.185	0.034	0.034
436	ASN	437	PRO	0.894	0.928	-0.034	0.034
77	MET	78	ASN	0.034	0.000	0.034	0.034
217	ILE	383	LYS	0.000	0.033	-0.033	0.033
422	TRP	426	TYR	0.167	0.134	0.032	0.032
352	GLN	353	ASN	1.695	1.727	-0.032	0.032
192	ILE	197	LEU	3.060	3.091	-0.031	0.031
199	VAL	203	THR	0.307	0.338	-0.031	0.031
212	ALA	215	SER	0.031	0.000	0.031	0.031
93	PRO	173	ASP	0.031	0.000	0.031	0.031
197	LEU	198	PRO	1.233	1.203	0.030	0.030
82	LEU	88	TYR	0.000	0.029	-0.029	0.029
42	ILE	46	VAL	0.474	0.445	0.029	0.029
380	SER	381	ARG	0.000	0.028	-0.028	0.028
122	TYR	209	ILE	3.045	3.018	0.028	0.028
27	VAL	32	SER	0.000	0.028	-0.028	0.028
83	TYR	174	GLY	0.464	0.437	0.027	0.027
414	ALA	415	PRO	0.790	0.764	0.026	0.026
112	MET	115	LEU	0.424	0.450	-0.026	0.026
37	THR	69	ASP	0.818	0.793	0.026	0.026
156	ALA	160	LEU	0.113	0.138	-0.026	0.026
100	LEU	159	ILE	1.884	1.858	0.025	0.025
156	ALA	161	PHE	0.022	0.047	-0.025	0.025
54	LEU	446	THR	2.482	2.457	0.025	0.025
48	ILE	62	LEU	0.077	0.053	0.024	0.024
60	TYR	140	ALA	0.000	0.024	-0.024	0.024
58	ASN	59	ASN	0.173	0.194	-0.021	0.021
62	LEU	65	LEU	0.021	0.000	0.021	0.021
401	ALA	402	PRO	0.753	0.774	-0.021	0.021
61	PHE	144	ILE	2.721	2.700	0.021	0.021
38	ILE	42	ILE	0.726	0.743	-0.017	0.017
127	LYS	128	PRO	0.086	0.102	-0.016	0.016
46	VAL	50	VAL	0.547	0.531	0.016	0.016
72	ILE	110	SER	0.014	0.000	0.014	0.014
393	LEU	397	ILE	0.014	0.000	0.014	0.014
270	VAL	278	GLU	0.000	0.012	-0.012	0.012
192	ILE	196	TYR	0.115	0.125	-0.011	0.011
124	CYS	132	PRO	0.010	0.000	0.010	0.010
166	VAL	170	THR	0.010	0.000	0.010	0.010
104	TYR	159	ILE	1.092	1.102	-0.010	0.010
138	LYS	142	MET	0.107	0.117	-0.009	0.009
215	SER	216	ARG	0.000	0.009	-0.009	0.009
54	LEU	450	THR	1.199	1.190	0.009	0.009
75	PHE	80	TYR	0.000	0.008	-0.008	0.008
39	ILE	43	LEU	0.740	0.732	0.008	0.008
156	ALA	157	PRO	0.813	0.821	-0.008	0.008
46	VAL	51	ASN	0.000	0.008	-0.008	0.008
33	LEU	37	THR	0.000	0.007	-0.007	0.007
146	ALA	151	SER	0.011	0.004	0.007	0.007
23	VAL	27	VAL	0.147	0.154	-0.007	0.007
279	GLU	375	LYS	0.000	0.007	-0.007	0.007
276	GLN	279	GLU	0.000	0.007	-0.007	0.007
204	VAL	208	HIS	1.104	1.111	-0.006	0.006
186	VAL	190	THR	0.223	0.229	-0.006	0.006
157	PRO	161	PHE	0.295	0.300	-0.005	0.005
61	PHE	143	MET	0.349	0.345	0.004	0.004
53	HIS	446	THR	0.255	0.251	0.003	0.003
26	ILE	84	THR	0.002	0.000	0.002	0.002
146	ALA	150	LEU	0.002	0.000	0.002	0.002
400	TRP	404	ASN	0.538	0.537	0.002	0.002
439	CYS	444	ASN	0.000	0.001	-0.001	0.001
437	PRO	440	TYR	0.000	0.001	-0.001	0.001

RRCS change distribution

0.12

Mean ΔRRCS

1.58

Std Dev

0.01

Median

Magnitude classification

High (|Δ| ≥ 5.0)

Medium (2.2 ≤ |Δ| < 5.0)

658

Low (|Δ| < 2.2)

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| ≥ 2.21, 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