ACM1

Gene CHRM1 Acetylcholine receptors (muscarinic) Aminergic receptors UniProt P11229

UniProt ↗ GPCRdb ↗ NCBI Gene ↗

721

Total Contact Pairs

Significant Changes

5.61

Max Increase

-10.18

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	ASN60 (2.39x39)	ARG123 (3.50x50)	0.000	10.182	-10.182	HIGH
2	THR172	GLN181	1.141	7.333	-6.192	HIGH
3	TYR208 (5.58x58)	LEU371 (6.41x41)	3.154	9.175	-6.020	HIGH
4	TYR208 (5.58x58)	LEU367 (6.37x37)	1.766	7.709	-5.942	HIGH
5	VAL395	TRP400 (7.35x34)	0.000	5.772	-5.772	HIGH
6	PHE355 (6.25x25)	LYS359 (6.29x29)	5.607	0.000	+5.607	HIGH
7	GLU216 (5.66x66)	LYS361 (6.31x31)	0.000	5.588	-5.588	HIGH
8	SER126 (3.53x53)	ARG134 (34.54x54)	0.000	5.185	-5.185	HIGH
9	THR95 (3.22x22)	ARG171	10.462	5.567	+4.895	MED
10	GLU278	PHE355 (6.25x25)	4.889	0.000	+4.889	MED
11	ARG134 (34.54x54)	GLU360 (6.30x30)	0.000	4.853	-4.853	MED
12	LEU131 (34.51x51)	TYR272	4.760	0.000	+4.760	MED
13	ARG436	ARG441	4.666	0.000	+4.666	MED
14	TRP378 (6.48x48)	CYS407 (7.42x41)	4.000	8.608	-4.608	MED
15	GLU229	LYS346	0.000	4.580	-4.580	MED
16	LEU431 (8.56x56)	ARG436	4.125	8.546	-4.421	MED
17	ALA419 (7.54x54)	ARG426 (8.51x51)	0.000	4.366	-4.366	MED
18	TYR133 (34.53x53)	ARG137 (34.57x57)	4.987	0.695	+4.291	MED
19	ASP122 (3.49x49)	ARG123 (3.50x50)	0.000	4.154	-4.154	MED
20	ASN410 (7.45x45)	ASN414 (7.49x49)	4.688	0.598	+4.090	MED
21	ALA219 (5.69x69)	GLU360 (6.30x30)	4.056	0.000	+4.056	MED
22	THR366 (6.36x36)	CYS421 (7.56x56)	0.879	4.850	-3.972	MED
23	SER78 (2.57x56)	TYR408 (7.43x42)	3.654	7.556	-3.902	MED
24	LEU420 (7.55x55)	ARG426 (8.51x51)	3.854	0.000	+3.854	MED
25	ASN53 (1.60x60)	TRP437	5.412	1.609	+3.803	MED
26	LEU222 (5.72x72)	THR354 (6.24x24)	0.000	3.688	-3.688	MED
27	LEU116 (3.43x43)	TYR418 (7.53x53)	3.603	0.000	+3.603	MED
28	CYS260	CYS262	3.533	0.000	+3.533	MED
29	LEU183	THR189 (5.39x40)	3.609	7.080	-3.470	MED
30	THR389 (6.59x59)	PHE390 (6.60x60)	0.008	3.257	-3.249	MED
31	PRO323	ASN324	0.000	3.184	-3.184	MED
32	PHE190 (5.40x41)	MET194 (5.44x45)	3.276	0.235	+3.041	MED
33	GLU55 (12.49x49)	LYS447	0.000	3.039	-3.039	MED
34	ARG123 (3.50x50)	TYR418 (7.53x53)	3.039	0.000	+3.039	MED
35	TYR198 (5.48x48)	ASN382 (6.52x52)	1.758	4.782	-3.024	MED
36	THR428 (8.53x53)	TRP437	4.955	1.946	+3.009	MED
37	TYR106 (3.33x33)	TYR381 (6.51x51)	4.684	1.680	+3.004	MED
38	ARG218	LEU357	0.000	2.991	-2.991	MED
39	ALA419 (7.54x54)	PHE425	2.969	0.080	+2.889	MED
40	TRP378 (6.48x48)	ASN410 (7.45x45)	6.720	3.872	+2.848	MED
41	ASP438	ARG440	3.688	6.525	-2.837	MED
42	SER120	TYR208 (5.58x58)	6.025	3.212	+2.814	MED
43	PHE374	ASN410 (7.45x45)	1.106	3.904	-2.798	MED
44	TYR106 (3.33x33)	ILE180	7.756	4.980	+2.776	MED
45	LEU56	PHE425	6.388	3.623	+2.765	MED
46	TRP437	TRP442	4.474	7.225	-2.751	MED
47	ARG243	GLN245	0.000	2.732	-2.732	MED
48	TYR124	THR128	4.861	2.143	+2.717	MED
49	SER287	LEU288	2.671	0.000	+2.671	MED
50	GLU170	GLN181	0.289	2.928	-2.640	MED
51	ARG426 (8.51x51)	ASP427	0.006	2.630	-2.624	MED
52	GLU279	ILE445	2.581	0.000	+2.581	MED
53	LEU288	THR289	2.567	0.000	+2.567	MED
54	THR54	LYS439	2.558	0.000	+2.558	MED
55	ASN324	THR325	0.666	3.223	-2.557	MED
56	GLN165	GLN181	4.538	2.008	+2.531	MED
57	ARG171	VAL173	0.217	2.702	-2.485	MED
58	LYS275	GLU277	0.236	2.686	-2.450	MED
59	ASN43	PRO415	3.153	5.590	-2.436	MED
60	GLY42	PRO415	1.769	4.197	-2.429	MED
61	PHE374	TRP378 (6.48x48)	4.474	6.901	-2.427	MED
62	GLN165	GLU170	1.977	4.384	-2.407	MED
63	PHE182	LEU183	0.000	2.397	-2.397	MED
64	MET79	TRP405	3.124	5.519	-2.395	MED
65	PRO186	THR389 (6.59x59)	2.774	5.167	-2.392	MED
66	MET194 (5.44x45)	TYR198 (5.48x48)	4.347	1.961	+2.386	MED
67	TYR106 (3.33x33)	TRP157	8.311	10.694	-2.382	MED
68	THR377	LEU406	7.368	9.745	-2.377	MED
69	MET79	TYR408 (7.43x42)	4.815	7.159	-2.344	MED
70	MET204	LEU371 (6.41x41)	0.363	2.702	-2.339	MED
71	LEU222 (5.72x72)	LYS353	0.000	2.334	-2.334	MED
72	GLN185	ILE188	0.700	3.033	-2.333	MED
73	ASN110	ALA196	2.637	0.339	+2.298	MED
74	ARG123 (3.50x50)	TYR208 (5.58x58)	2.293	0.000	+2.293	MED
75	PHE63	ASP122 (3.49x49)	4.826	2.542	+2.284	MED
76	TRP91	TRP101	8.363	6.083	+2.280	MED
77	SER132	LYS136	2.270	0.000	+2.270	MED
78	ASN61	PHE425	3.096	0.851	+2.245	MED
79	TYR212	ALA364	2.244	0.000	+2.244	MED
80	LYS362	CYS421 (7.56x56)	0.000	2.232	-2.232	MED
81	LEU64	TYR418 (7.53x53)	1.622	3.839	-2.217	MED
82	LEU183	THR389 (6.59x59)	2.211	0.000	+2.211	MED
83	TYR62	PRO139	0.172	2.382	-2.210	MED
84	SER126 (3.53x53)	TYR133 (34.53x53)	4.369	2.179	+2.190	MED
85	ARG320	SER321	0.179	2.339	-2.160	MED
86	ILE370	TYR418 (7.53x53)	3.070	0.920	+2.150	MED
87	VAL59	THR138	0.063	2.211	-2.147	MED
88	LEU431 (8.56x56)	TRP442	0.005	2.126	-2.121	MED
89	ALA160	PHE182	2.077	4.170	-2.094	MED
90	VAL127	ARG218	5.228	7.298	-2.070	MED
91	TRP101	LEU102	2.988	0.957	+2.031	MED
92	TYR381 (6.51x51)	TRP400 (7.35x34)	0.698	2.721	-2.023	MED
93	LEU81	TRP101	3.708	1.686	+2.022	MED
94	VAL113	TRP378 (6.48x48)	2.020	0.000	+2.020	MED
95	LEU222 (5.72x72)	GLN226	0.000	2.019	-2.019	MED
96	PHE63	LEU118	2.889	0.895	+1.993	MED
97	TYR198 (5.48x48)	LEU386	2.667	4.660	-1.993	MED
98	ARG243	SER244	1.986	0.000	+1.986	MED
99	ASP122 (3.49x49)	TYR133 (34.53x53)	6.952	5.006	+1.946	LOW
100	TRP164	PHE182	8.827	6.907	+1.919	LOW

Transmembrane domain analysis

Active-favoring residues form stronger contacts in the active state (positive ΔRRCS). Inactive-favoring residues form stronger contacts in the inactive state (negative ΔRRCS). Only residues with |ΔRRCS| ≥ 1.96 are shown (per-receptor significance threshold = max(mean(|Δ|) + σ, 0.2)).

Segment	Range	Active-favoring residues	Count	Inactive-favoring residues	Count
TM1	53-53	53 (3.8)	1	-	0
TM2	60-78	-	0	60 (-10.2), 78 (-3.9)	2
TM3	95-126	95 (4.9), 116 (3.6), 106 (3.0)	3	123 (-10.2), 126 (-5.2), 122 (-4.2)	3
TM4	-	-	0	-	0
TM5	189-222	219 (4.1), 190 (3.0), 194 (3.0)	3	208 (-6.0), 216 (-5.6), 222 (-3.7), 189 (-3.5), 198 (-3.0)	5
TM6	354-390	355 (5.6), 359 (5.6), 381 (3.0)	3	371 (-6.0), 367 (-5.9), 361 (-5.6), 360 (-4.9), 378 (-4.6), 366 (-4.0), 354 (-3.7), 389 (-3.2), 390 (-3.2), 382 (-3.0)	10
TM7	400-421	410 (4.1), 414 (4.1), 420 (3.9), 418 (3.6)	4	400 (-5.8), 407 (-4.6), 419 (-4.4), 421 (-4.0), 408 (-3.9)	5
Intracellular / Extracellular loops & H8
ICL1	55-55	-	0	55 (-3.0)	1
ICL2	131-137	131 (4.8), 133 (4.3), 137 (4.3)	3	134 (-5.2)	1
ICL3	229-346	278 (4.9), 272 (4.8), 260 (3.5), 262 (3.5)	4	229 (-4.6), 346 (-4.6), 323 (-3.2), 324 (-3.2)	4
ECL1	-	-	0	-	0
ECL2	171-183	171 (4.9)	1	172 (-6.2), 181 (-6.2), 183 (-3.5)	3
ECL3	395-395	-	0	395 (-5.8)	1
H8	426-431	428 (3.0)	1	431 (-4.4), 426 (-4.4)	2

Interactive visualizations

ΔRRCS distribution

Active vs inactive comparison

Residue-wise changes

TM domain breakdown

Variants of interest

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

Position	Protein change	DNA change	Allele freq	Het / Hom	ΔRRCS	AM score	Pathogenicity	Conservation	dbSNP
123	p.Arg123His	c.368G>A	6.84e-07	1 / 0	10.18	0.994	PATHOGENIC	0.98	rs2085866530
123	p.Arg123Cys	c.367C>T	6.57e-06	1 / 0	10.18	-	nan	-	rs2085866551
367	p.Leu367Pro	c.1100T>C	6.84e-07	1 / 0	5.94	0.999	PATHOGENIC	0.72
395	p.Val395Leu	c.1183G>C	6.84e-07	1 / 0	5.77	0.737	PATHOGENIC	0.80	rs1175739065
395	p.Val395Ile	c.1183G>A	6.57e-06	1 / 0	5.77	-	nan	-	rs1175739065
359	p.Lys359Glu	c.1075A>G	6.84e-07	1 / 0	5.61	0.967	PATHOGENIC	0.64
355	p.Phe355Leu	c.1065C>A	1.37e-06	2 / 0	5.61	0.723	PATHOGENIC	0.26	rs1399306313
216	p.Glu216Gln	c.646G>C	6.84e-07	1 / 0	5.59	0.141	BENIGN	0.53	rs775481630
361	p.Lys361Arg	c.1082A>G	6.84e-07	1 / 0	5.59	0.135	BENIGN	0.67	rs777308162
134	p.Arg134Pro	c.401G>C	6.84e-07	1 / 0	5.18	0.976	PATHOGENIC	0.72
134	p.Arg134His	c.401G>A	2.74e-06	4 / 0	5.18	-	nan	-	rs759707133
134	p.Arg134Cys	c.400C>T	6.84e-07	1 / 0	5.18	-	nan	-	rs1301956324
171	p.Arg171Gln	c.512G>A	2.05e-06	3 / 0	4.90	0.850	PATHOGENIC	0.86	rs1382129041
95	p.Thr95Met	c.284C>T	1.03e-05	13 / 1	4.90	0.160	BENIGN	0.53	rs1007009594
171	p.Arg171Trp	c.511C>T	2.74e-06	4 / 0	4.90	-	nan	-	rs2085865442
95	p.Thr95Pro	c.283A>C	6.84e-07	1 / 0	4.90	-	nan	-
131	p.Leu131Arg	c.392T>G	2.74e-06	4 / 0	4.76	0.987	PATHOGENIC	0.85
436	p.Arg436Leu	c.1307G>T	6.84e-07	1 / 0	4.67	0.572	PATHOGENIC	0.61	rs369705923
441	p.Arg441His	c.1322G>A	4.10e-06	6 / 0	4.67	0.178	BENIGN	0.71	rs1217695022
441	p.Arg441Cys	c.1321C>T	3.42e-06	5 / 0	4.67	-	nan	-	rs1258843299
436	p.Arg436His	c.1307G>A	7.52e-06	11 / 0	4.67	-	nan	-	rs369705923
436	p.Arg436Cys	c.1306C>T	1.37e-06	2 / 0	4.67	-	nan	-	rs1298933700
407	p.Cys407Gly	c.1219T>G	1.38e-04	202 / 0	4.61	0.976	PATHOGENIC	0.94	rs779975794
229	p.Glu229Asp	c.687G>T	1.37e-06	2 / 0	4.58	0.129	BENIGN	0.42	rs1268099406
229	p.Glu229Lys	c.685G>A	1.37e-06	2 / 0	4.58	-	nan	-	rs909781711
419	p.Ala419Pro	c.1255G>C	6.84e-07	1 / 0	4.37	0.988	PATHOGENIC	0.92
426	p.Arg426Gln	c.1277G>A	1.09e-05	14 / 1	4.37	0.312	BENIGN	0.80	rs752313223
426	p.Arg426Trp	c.1276C>T	6.57e-06	1 / 0	4.37	-	nan	-	rs762373862
419	p.Ala419Thr	c.1255G>A	2.74e-06	4 / 0	4.37	-	nan	-	rs1449918441
419	p.Ala419Ser	c.1255G>T	6.84e-07	1 / 0	4.37	-	nan	-	rs1449918441
133	p.Tyr133His	c.397T>C	6.84e-07	1 / 0	4.29	0.998	PATHOGENIC	1.00	rs1373703509
137	p.Arg137His	c.410G>A	1.37e-06	2 / 0	4.29	0.973	PATHOGENIC	0.91	rs2085866239
420	p.Leu420Ile	c.1258C>A	6.56e-06	1 / 0	3.85	0.632	PATHOGENIC	0.80	rs534575167
354	p.Thr354Asn	c.1061C>A	6.23e-05	91 / 0	3.69	0.142	BENIGN	0.35	rs377511832
262	p.Cys262Ser	c.785G>C	6.86e-07	1 / 0	3.53	0.174	BENIGN	0.36
260	p.Cys260Tyr	c.779G>A	2.06e-06	3 / 0	3.53	0.171	BENIGN	0.35	rs2085863094
183	p.Leu183Pro	c.548T>C	6.84e-07	1 / 0	3.47	0.990	PATHOGENIC	0.67	rs1163383446
324	p.Asn324Ser	c.971A>G	7.76e-05	113 / 0	3.18	0.066	BENIGN	0.41	rs143521986
324	p.Asn324Tyr	c.970A>T	6.86e-07	1 / 0	3.18	-	nan	-
55	p.Glu55Val	c.164A>T	6.84e-07	1 / 0	3.04	0.626	PATHOGENIC	0.56
447	p.Lys447Arg	c.1340A>G	6.84e-07	1 / 0	3.04	0.063	BENIGN	0.68
55	p.Glu55Lys	c.163G>A	6.84e-07	1 / 0	3.04	-	nan	-	rs759819719

Complete RRCS results

Res1	AA1	Res2	AA2	Active RRCS	Inactive RRCS	ΔRRCS	\|ΔRRCS\|
60	ASN	123	ARG	0.000	10.182	-10.182	10.182
172	THR	181	GLN	1.141	7.333	-6.192	6.192
208	TYR	371	LEU	3.154	9.175	-6.020	6.020
208	TYR	367	LEU	1.766	7.709	-5.942	5.942
395	VAL	400	TRP	0.000	5.772	-5.772	5.772
355	PHE	359	LYS	5.607	0.000	5.607	5.607
216	GLU	361	LYS	0.000	5.588	-5.588	5.588
126	SER	134	ARG	0.000	5.185	-5.185	5.185
95	THR	171	ARG	10.462	5.567	4.895	4.895
278	GLU	355	PHE	4.889	0.000	4.889	4.889
134	ARG	360	GLU	0.000	4.853	-4.853	4.853
131	LEU	272	TYR	4.760	0.000	4.760	4.760
436	ARG	441	ARG	4.666	0.000	4.666	4.666
378	TRP	407	CYS	4.000	8.608	-4.608	4.608
229	GLU	346	LYS	0.000	4.580	-4.580	4.580
431	LEU	436	ARG	4.125	8.546	-4.421	4.421
419	ALA	426	ARG	0.000	4.366	-4.366	4.366
133	TYR	137	ARG	4.987	0.695	4.291	4.291
122	ASP	123	ARG	0.000	4.154	-4.154	4.154
410	ASN	414	ASN	4.688	0.598	4.090	4.090
219	ALA	360	GLU	4.056	0.000	4.056	4.056
366	THR	421	CYS	0.879	4.850	-3.972	3.972
78	SER	408	TYR	3.654	7.556	-3.902	3.902
420	LEU	426	ARG	3.854	0.000	3.854	3.854
53	ASN	437	TRP	5.412	1.609	3.803	3.803
222	LEU	354	THR	0.000	3.688	-3.688	3.688
116	LEU	418	TYR	3.603	0.000	3.603	3.603
260	CYS	262	CYS	3.533	0.000	3.533	3.533
183	LEU	189	THR	3.609	7.080	-3.470	3.470
389	THR	390	PHE	0.008	3.257	-3.249	3.249
323	PRO	324	ASN	0.000	3.184	-3.184	3.184
190	PHE	194	MET	3.276	0.235	3.041	3.041
55	GLU	447	LYS	0.000	3.039	-3.039	3.039
123	ARG	418	TYR	3.039	0.000	3.039	3.039
198	TYR	382	ASN	1.758	4.782	-3.024	3.024
428	THR	437	TRP	4.955	1.946	3.009	3.009
106	TYR	381	TYR	4.684	1.680	3.004	3.004
218	ARG	357	LEU	0.000	2.991	-2.991	2.991
419	ALA	425	PHE	2.969	0.080	2.889	2.889
378	TRP	410	ASN	6.720	3.872	2.848	2.848
438	ASP	440	ARG	3.688	6.525	-2.837	2.837
120	SER	208	TYR	6.025	3.212	2.814	2.814
374	PHE	410	ASN	1.106	3.904	-2.798	2.798
106	TYR	180	ILE	7.756	4.980	2.776	2.776
56	LEU	425	PHE	6.388	3.623	2.765	2.765
437	TRP	442	TRP	4.474	7.225	-2.751	2.751
243	ARG	245	GLN	0.000	2.732	-2.732	2.732
124	TYR	128	THR	4.861	2.143	2.717	2.717
287	SER	288	LEU	2.671	0.000	2.671	2.671
170	GLU	181	GLN	0.289	2.928	-2.640	2.640
426	ARG	427	ASP	0.006	2.630	-2.624	2.624
279	GLU	445	ILE	2.581	0.000	2.581	2.581
288	LEU	289	THR	2.567	0.000	2.567	2.567
54	THR	439	LYS	2.558	0.000	2.558	2.558
324	ASN	325	THR	0.666	3.223	-2.557	2.557
165	GLN	181	GLN	4.538	2.008	2.531	2.531
171	ARG	173	VAL	0.217	2.702	-2.485	2.485
275	LYS	277	GLU	0.236	2.686	-2.450	2.450
43	ASN	415	PRO	3.153	5.590	-2.436	2.436
42	GLY	415	PRO	1.769	4.197	-2.429	2.429
374	PHE	378	TRP	4.474	6.901	-2.427	2.427
165	GLN	170	GLU	1.977	4.384	-2.407	2.407
182	PHE	183	LEU	0.000	2.397	-2.397	2.397
79	MET	405	TRP	3.124	5.519	-2.395	2.395
186	PRO	389	THR	2.774	5.167	-2.392	2.392
194	MET	198	TYR	4.347	1.961	2.386	2.386
106	TYR	157	TRP	8.311	10.694	-2.382	2.382
377	THR	406	LEU	7.368	9.745	-2.377	2.377
79	MET	408	TYR	4.815	7.159	-2.344	2.344
204	MET	371	LEU	0.363	2.702	-2.339	2.339
222	LEU	353	LYS	0.000	2.334	-2.334	2.334
185	GLN	188	ILE	0.700	3.033	-2.333	2.333
110	ASN	196	ALA	2.637	0.339	2.298	2.298
123	ARG	208	TYR	2.293	0.000	2.293	2.293
63	PHE	122	ASP	4.826	2.542	2.284	2.284
91	TRP	101	TRP	8.363	6.083	2.280	2.280
132	SER	136	LYS	2.270	0.000	2.270	2.270
61	ASN	425	PHE	3.096	0.851	2.245	2.245
212	TYR	364	ALA	2.244	0.000	2.244	2.244
362	LYS	421	CYS	0.000	2.232	-2.232	2.232
64	LEU	418	TYR	1.622	3.839	-2.217	2.217
183	LEU	389	THR	2.211	0.000	2.211	2.211
62	TYR	139	PRO	0.172	2.382	-2.210	2.210
126	SER	133	TYR	4.369	2.179	2.190	2.190
320	ARG	321	SER	0.179	2.339	-2.160	2.160
370	ILE	418	TYR	3.070	0.920	2.150	2.150
59	VAL	138	THR	0.063	2.211	-2.147	2.147
431	LEU	442	TRP	0.005	2.126	-2.121	2.121
160	ALA	182	PHE	2.077	4.170	-2.094	2.094
127	VAL	218	ARG	5.228	7.298	-2.070	2.070
101	TRP	102	LEU	2.988	0.957	2.031	2.031
381	TYR	400	TRP	0.698	2.721	-2.023	2.023
81	LEU	101	TRP	3.708	1.686	2.022	2.022
113	VAL	378	TRP	2.020	0.000	2.020	2.020
222	LEU	226	GLN	0.000	2.019	-2.019	2.019
63	PHE	118	LEU	2.889	0.895	1.993	1.993
198	TYR	386	LEU	2.667	4.660	-1.993	1.993
243	ARG	244	SER	1.986	0.000	1.986	1.986
122	ASP	133	TYR	6.952	5.006	1.946	1.946
164	TRP	182	PHE	8.827	6.907	1.919	1.919
91	TRP	97	ALA	1.074	2.992	-1.918	1.918
415	PRO	420	LEU	1.907	0.000	1.907	1.907
328	ARG	329	PRO	2.450	4.326	-1.876	1.876
205	CYS	371	LEU	1.969	0.127	1.843	1.843
82	TYR	404	TYR	7.559	5.724	1.835	1.835
276	GLU	348	GLN	0.000	1.795	-1.795	1.795
161	ILE	180	ILE	0.318	2.108	-1.790	1.790
109	SER	378	TRP	3.663	1.881	1.782	1.782
182	PHE	189	THR	1.981	0.268	1.713	1.713
53	ASN	442	TRP	0.031	1.732	-1.701	1.701
418	TYR	425	PHE	0.000	1.701	-1.701	1.701
423	LYS	427	ASP	2.059	3.757	-1.698	1.698
52	VAL	437	TRP	7.228	8.922	-1.694	1.694
111	ALA	150	TRP	1.763	3.444	-1.682	1.682
278	GLU	359	LYS	1.678	0.000	1.678	1.678
197	PHE	198	TYR	2.778	4.432	-1.654	1.654
20	LYS	401	GLU	2.974	4.616	-1.642	1.642
356	SER	360	GLU	0.000	1.634	-1.634	1.634
123	ARG	367	LEU	0.862	2.457	-1.595	1.595
156	LEU	157	TRP	2.092	3.687	-1.594	1.594
289	THR	290	SER	2.007	0.438	1.568	1.568
182	PHE	188	ILE	0.309	1.868	-1.559	1.559
59	VAL	137	ARG	1.664	3.206	-1.542	1.542
318	PRO	319	PRO	0.309	1.793	-1.485	1.485
208	TYR	368	SER	0.000	1.481	-1.481	1.481
106	TYR	404	TYR	5.230	3.753	1.477	1.477
125	PHE	133	TYR	9.754	8.280	1.475	1.475
71	ASP	112	SER	3.092	1.640	1.452	1.452
17	ALA	89	GLY	0.000	1.435	-1.435	1.435
204	MET	374	PHE	2.876	1.452	1.424	1.424
102	LEU	180	ILE	0.319	1.730	-1.411	1.411
347	GLU	351	LYS	2.296	3.696	-1.399	1.399
107	VAL	153	SER	2.074	3.471	-1.397	1.397
129	ARG	132	SER	0.000	1.397	-1.397	1.397
39	THR	79	MET	1.757	3.154	-1.397	1.397
115	ASN	150	TRP	2.127	0.733	1.394	1.394
214	GLU	218	ARG	6.195	7.578	-1.383	1.383
101	TRP	105	ASP	0.271	1.642	-1.371	1.371
164	TRP	185	GLN	1.922	0.560	1.362	1.362
67	LEU	418	TYR	0.842	2.200	-1.358	1.358
130	PRO	135	ALA	0.000	1.354	-1.354	1.354
119	ILE	123	ARG	1.436	0.091	1.346	1.346
442	TRP	445	ILE	0.000	1.313	-1.313	1.313
286	GLU	287	SER	1.301	0.000	1.301	1.301
129	ARG	134	ARG	0.000	1.298	-1.298	1.298
217	ASN	220	ARG	1.298	0.000	1.298	1.298
252	PRO	253	GLU	1.377	0.091	1.285	1.285
35	LEU	79	MET	1.900	0.623	1.277	1.277
46	VAL	418	TYR	0.000	1.273	-1.273	1.273
310	GLU	311	ALA	0.000	1.251	-1.251	1.251
86	LEU	401	GLU	2.435	3.686	-1.251	1.251
63	PHE	145	MET	0.121	1.363	-1.242	1.242
66	SER	146	ILE	2.382	3.606	-1.224	1.224
251	SER	252	PRO	1.301	0.086	1.216	1.216
226	GLN	354	THR	0.000	1.210	-1.210	1.210
197	PHE	374	PHE	0.296	1.495	-1.199	1.199
215	THR	360	GLU	1.182	0.000	1.182	1.182
88	MET	92	ALA	0.000	1.181	-1.181	1.181
371	LEU	375	ILE	1.179	0.000	1.179	1.179
50	PHE	61	ASN	1.359	2.532	-1.173	1.173
377	THR	410	ASN	5.777	4.608	1.169	1.169
222	LEU	357	LEU	0.000	1.167	-1.167	1.167
91	TRP	176	GLY	4.571	5.731	-1.161	1.161
285	MET	286	GLU	1.151	0.000	1.151	1.151
91	TRP	177	GLN	0.098	1.245	-1.148	1.148
190	PHE	389	THR	0.000	1.139	-1.139	1.139
219	ALA	361	LYS	0.000	1.139	-1.139	1.139
384	MET	395	VAL	1.272	2.410	-1.138	1.138
165	GLN	171	ARG	4.381	5.492	-1.111	1.111
290	SER	291	SER	0.089	1.199	-1.110	1.110
61	ASN	422	ASN	1.102	0.000	1.102	1.102
47	LEU	65	LEU	2.227	3.325	-1.099	1.099
419	ALA	429	PHE	0.076	1.174	-1.098	1.098
325	THR	326	VAL	0.000	1.093	-1.093	1.093
417	CYS	418	TYR	1.088	0.000	1.088	1.088
96	LEU	100	LEU	0.560	1.647	-1.087	1.087
67	LEU	115	ASN	2.898	1.814	1.084	1.084
46	VAL	429	PHE	3.519	2.441	1.078	1.078
420	LEU	429	PHE	1.068	0.000	1.068	1.068
98	CYS	178	CYS	5.620	6.675	-1.056	1.056
208	TYR	418	TYR	1.051	0.000	1.051	1.051
122	ASP	126	SER	1.048	0.000	1.048	1.048
392	LYS	393	ASP	0.504	1.549	-1.044	1.044
370	ILE	417	CYS	2.579	1.536	1.043	1.043
438	ASP	441	ARG	1.892	0.856	1.036	1.036
67	LEU	116	LEU	2.063	1.032	1.032	1.032
74	ILE	411	SER	2.789	1.759	1.030	1.030
342	LYS	343	PRO	1.026	0.000	1.026	1.026
77	PHE	104	LEU	0.347	1.370	-1.023	1.023
66	SER	115	ASN	7.273	6.255	1.018	1.018
117	LEU	200	PRO	1.376	0.359	1.017	1.017
381	TYR	385	VAL	3.519	2.523	0.996	0.996
71	ASP	414	ASN	5.166	4.193	0.973	0.973
314	PRO	315	THR	0.000	0.969	-0.969	0.969
119	ILE	418	TYR	0.968	0.000	0.968	0.968
414	ASN	418	TYR	0.526	1.493	-0.966	0.966
197	PHE	379	THR	3.912	2.974	0.938	0.938
71	ASP	411	SER	9.900	10.837	-0.938	0.938
75	GLY	80	ASN	1.044	1.976	-0.932	0.932
311	ALA	312	GLN	0.980	1.898	-0.919	0.919
211	ILE	367	LEU	0.905	0.000	0.905	0.905
216	GLU	220	ARG	0.898	0.000	0.898	0.898
45	LEU	429	PHE	5.374	4.479	0.895	0.895
327	LYS	328	ARG	0.225	1.119	-0.895	0.895
240	SER	241	SER	0.000	0.884	-0.884	0.884
105	ASP	404	TYR	2.040	2.918	-0.877	0.877
74	ILE	108	ALA	2.194	1.325	0.869	0.869
122	ASP	137	ARG	5.122	5.978	-0.856	0.856
173	VAL	179	TYR	7.977	7.123	0.853	0.853
245	GLN	246	PRO	1.242	2.090	-0.847	0.847
119	ILE	367	LEU	0.000	0.846	-0.846	0.846
197	PHE	378	TRP	4.712	3.866	0.846	0.846
241	SER	242	GLU	1.661	0.817	0.844	0.844
25	VAL	87	LEU	2.256	3.094	-0.838	0.838
36	SER	75	GLY	2.977	2.144	0.833	0.833
43	ASN	411	SER	1.232	2.063	-0.830	0.830
17	ALA	88	MET	0.000	0.817	-0.817	0.817
128	THR	218	ARG	0.995	1.810	-0.815	0.815
180	ILE	183	LEU	1.803	2.613	-0.810	0.810
384	MET	403	GLY	0.000	0.806	-0.806	0.806
179	TYR	184	SER	0.000	0.805	-0.805	0.805
189	THR	389	THR	2.383	1.579	0.803	0.803
82	TYR	401	GLU	2.075	2.877	-0.802	0.802
197	PHE	201	VAL	3.451	2.652	0.799	0.799
32	THR	405	TRP	6.278	7.075	-0.798	0.798
53	ASN	56	LEU	3.233	2.436	0.797	0.797
116	LEU	370	ILE	0.000	0.795	-0.795	0.795
116	LEU	374	PHE	1.612	2.404	-0.792	0.792
225	LEU	353	LYS	0.000	0.789	-0.789	0.789
49	SER	432	LEU	2.301	1.515	0.786	0.786
123	ARG	370	ILE	0.783	0.000	0.783	0.783
416	MET	420	LEU	0.780	0.000	0.780	0.780
118	LEU	146	ILE	1.489	0.709	0.779	0.779
186	PRO	390	PHE	0.779	0.000	0.779	0.779
415	PRO	429	PHE	0.000	0.761	-0.761	0.761
397	GLU	400	TRP	0.284	1.037	-0.754	0.754
82	TYR	86	LEU	2.872	3.621	-0.749	0.749
421	CYS	426	ARG	0.748	0.000	0.748	0.748
434	LEU	436	ARG	1.364	0.617	0.746	0.746
50	PHE	62	TYR	3.260	4.006	-0.745	0.745
56	LEU	424	ALA	2.370	1.636	0.734	0.734
76	THR	77	PHE	1.323	2.057	-0.734	0.734
106	TYR	161	ILE	1.466	0.741	0.725	0.725
101	TRP	408	TYR	0.356	1.080	-0.724	0.724
112	SER	414	ASN	0.768	0.047	0.720	0.720
136	LYS	141	ARG	4.502	3.784	0.718	0.718
190	PHE	390	PHE	0.000	0.717	-0.717	0.717
161	ILE	182	PHE	1.147	1.864	-0.717	0.717
85	TYR	176	GLY	1.272	0.569	0.703	0.703
39	THR	412	THR	7.238	6.541	0.698	0.698
85	TYR	178	CYS	1.987	1.290	0.697	0.697
63	PHE	146	ILE	3.245	2.551	0.694	0.694
373	ALA	410	ASN	0.000	0.690	-0.690	0.690
295	GLU	440	ARG	0.685	0.000	0.685	0.685
298	SER	299	GLU	0.000	0.683	-0.683	0.683
53	ASN	55	GLU	2.555	1.878	0.677	0.677
63	PHE	142	ALA	2.045	2.722	-0.676	0.676
208	TYR	211	ILE	1.013	0.345	0.667	0.667
370	ILE	414	ASN	0.000	0.665	-0.665	0.665
29	GLY	87	LEU	0.584	1.249	-0.665	0.665
20	LYS	86	LEU	0.000	0.662	-0.662	0.662
98	CYS	99	ASP	0.247	0.908	-0.661	0.661
376	LEU	406	LEU	0.211	0.871	-0.660	0.660
121	PHE	125	PHE	1.190	1.845	-0.655	0.655
49	SER	429	PHE	3.211	2.558	0.653	0.653
377	THR	407	CYS	2.435	1.794	0.641	0.641
322	SER	323	PRO	2.176	2.817	-0.641	0.641
113	VAL	374	PHE	1.024	1.664	-0.640	0.640
157	TRP	196	ALA	0.986	0.348	0.638	0.638
209	TRP	212	TYR	0.784	0.152	0.632	0.632
74	ILE	79	MET	4.314	3.684	0.630	0.630
437	TRP	439	LYS	0.000	0.628	-0.628	0.628
124	TYR	210	ARG	3.142	3.766	-0.624	0.624
272	TYR	274	TRP	0.000	0.623	-0.623	0.623
63	PHE	115	ASN	0.000	0.618	-0.618	0.618
148	LEU	152	VAL	0.616	0.000	0.616	0.616
50	PHE	56	LEU	2.701	3.316	-0.614	0.614
385	VAL	400	TRP	2.605	3.219	-0.614	0.614
404	TYR	408	TYR	3.971	4.584	-0.613	0.613
171	ARG	181	GLN	3.486	4.099	-0.613	0.613
405	TRP	408	TYR	2.096	2.701	-0.605	0.605
51	LYS	57	LYS	2.894	3.490	-0.596	0.596
201	VAL	374	PHE	1.287	0.691	0.596	0.596
409	VAL	413	ILE	0.320	0.915	-0.595	0.595
423	LYS	426	ARG	0.000	0.594	-0.594	0.594
20	LYS	28	ILE	0.968	0.376	0.593	0.593
46	VAL	419	ALA	0.592	0.000	0.592	0.592
254	THR	255	PRO	1.209	1.797	-0.589	0.589
82	TYR	408	TYR	3.639	3.052	0.588	0.588
50	PHE	57	LYS	4.175	4.762	-0.587	0.587
82	TYR	405	TRP	3.558	4.137	-0.579	0.579
86	LEU	405	TRP	1.174	1.749	-0.575	0.575
133	TYR	145	MET	0.064	0.634	-0.569	0.569
212	TYR	216	GLU	3.033	2.465	0.569	0.569
84	THR	88	MET	1.297	0.731	0.566	0.566
118	LEU	149	ALA	0.163	0.728	-0.566	0.566
28	ILE	87	LEU	0.000	0.564	-0.564	0.564
85	TYR	177	GLN	1.732	1.178	0.554	0.554
164	TRP	168	VAL	3.058	2.509	0.549	0.549
215	THR	361	LYS	0.000	0.546	-0.546	0.546
391	CYS	394	CYS	1.680	2.223	-0.543	0.543
40	VAL	72	LEU	1.791	2.333	-0.542	0.542
177	GLN	179	TYR	3.045	2.503	0.542	0.542
375	ILE	379	THR	1.377	0.841	0.536	0.536
56	LEU	61	ASN	5.244	5.778	-0.534	0.534
276	GLU	359	LYS	0.534	0.000	0.534	0.534
20	LYS	24	GLN	0.748	0.214	0.533	0.533
88	MET	90	HIS	0.741	1.273	-0.531	0.531
343	PRO	346	LYS	0.531	0.000	0.531	0.531
116	LEU	414	ASN	0.529	0.000	0.529	0.529
110	ASN	114	MET	0.712	1.234	-0.522	0.522
60	ASN	61	ASN	0.382	0.902	-0.520	0.520
102	LEU	179	TYR	2.117	2.636	-0.520	0.520
45	LEU	432	LEU	0.788	1.305	-0.517	0.517
47	LEU	68	ALA	0.231	0.743	-0.512	0.512
57	LYS	62	TYR	0.511	0.000	0.511	0.511
396	PRO	399	LEU	0.892	1.402	-0.511	0.511
125	PHE	130	PRO	0.740	0.232	0.508	0.508
447	LYS	451	SER	0.000	0.505	-0.505	0.505
114	MET	117	LEU	0.692	0.190	0.502	0.502
222	LEU	360	GLU	0.501	0.000	0.501	0.501
98	CYS	171	ARG	0.440	0.941	-0.501	0.501
47	LEU	69	CYS	0.612	1.108	-0.496	0.496
170	GLU	172	THR	0.266	0.762	-0.496	0.496
66	SER	150	TRP	3.380	2.894	0.486	0.486
134	ARG	356	SER	0.000	0.483	-0.483	0.483
244	SER	245	GLN	0.476	0.000	0.476	0.476
213	ARG	217	ASN	0.692	0.216	0.476	0.476
43	ASN	72	LEU	1.972	1.497	0.475	0.475
380	PRO	406	LEU	0.974	1.449	-0.475	0.475
32	THR	83	THR	4.005	4.480	-0.475	0.475
413	ILE	417	CYS	0.224	0.699	-0.474	0.474
118	LEU	145	MET	3.242	2.771	0.471	0.471
102	LEU	161	ILE	1.525	1.992	-0.467	0.467
82	TYR	101	TRP	2.548	3.014	-0.465	0.465
206	THR	210	ARG	1.146	0.687	0.459	0.459
125	PHE	129	ARG	0.000	0.459	-0.459	0.459
219	ALA	357	LEU	0.290	0.749	-0.458	0.458
194	MET	386	LEU	0.455	0.000	0.455	0.455
77	PHE	81	LEU	0.000	0.451	-0.451	0.451
114	MET	149	ALA	1.591	1.141	0.450	0.450
226	GLN	353	LYS	0.450	0.000	0.450	0.450
56	LEU	428	THR	0.835	0.386	0.449	0.449
164	TRP	181	GLN	2.610	2.162	0.448	0.448
116	LEU	204	MET	1.767	2.214	-0.447	0.447
107	VAL	154	PHE	2.677	3.123	-0.447	0.447
81	LEU	93	LEU	0.000	0.445	-0.445	0.445
99	ASP	181	GLN	0.443	0.000	0.443	0.443
49	SER	56	LEU	1.707	2.149	-0.442	0.442
129	ARG	133	TYR	0.000	0.441	-0.441	0.441
115	ASN	146	ILE	0.042	0.479	-0.437	0.437
53	ASN	428	THR	2.860	2.427	0.433	0.433
193	ALA	385	VAL	0.000	0.433	-0.433	0.433
50	PHE	65	LEU	3.567	3.137	0.430	0.430
91	TRP	178	CYS	3.205	2.777	0.428	0.428
90	HIS	176	GLY	3.898	3.472	0.427	0.427
428	THR	442	TRP	0.000	0.425	-0.425	0.425
114	MET	153	SER	1.305	0.884	0.421	0.421
156	LEU	196	ALA	0.420	0.000	0.420	0.420
183	LEU	385	VAL	0.419	0.000	0.419	0.419
74	ILE	78	SER	0.876	1.289	-0.413	0.413
128	THR	129	ARG	0.690	1.103	-0.413	0.413
99	ASP	171	ARG	7.531	7.118	0.413	0.413
91	TRP	93	LEU	2.621	3.034	-0.413	0.413
70	ALA	108	ALA	0.962	1.374	-0.412	0.412
381	TYR	404	TYR	3.040	3.451	-0.410	0.410
197	PHE	382	ASN	11.831	12.239	-0.408	0.408
110	ASN	153	SER	7.700	7.297	0.403	0.403
110	ASN	156	LEU	0.415	0.015	0.400	0.400
349	LEU	353	LYS	0.453	0.061	0.393	0.393
82	TYR	85	TYR	0.400	0.783	-0.383	0.383
99	ASP	161	ILE	0.752	1.135	-0.383	0.383
36	SER	80	ASN	4.768	4.385	0.383	0.383
60	ASN	122	ASP	0.953	0.571	0.381	0.381
190	PHE	386	LEU	1.395	1.014	0.380	0.380
35	LEU	409	VAL	0.034	0.414	-0.379	0.379
172	THR	179	TYR	1.463	1.837	-0.374	0.374
67	LEU	112	SER	2.502	2.875	-0.372	0.372
174	LEU	179	TYR	0.354	0.722	-0.368	0.368
381	TYR	403	GLY	1.817	1.449	0.367	0.367
216	GLU	219	ALA	0.000	0.365	-0.365	0.365
107	VAL	157	TRP	0.745	1.104	-0.359	0.359
20	LYS	25	VAL	0.835	1.192	-0.357	0.357
222	LEU	350	ALA	0.000	0.356	-0.356	0.356
388	SER	400	TRP	1.302	1.655	-0.353	0.353
381	TYR	382	ASN	1.336	0.983	0.353	0.353
146	ILE	150	TRP	0.694	1.046	-0.352	0.352
45	LEU	433	LEU	0.729	1.080	-0.350	0.350
60	ASN	137	ARG	5.275	4.926	0.349	0.349
120	SER	204	MET	2.333	2.682	-0.348	0.348
455	THR	456	PRO	0.755	0.408	0.347	0.347
48	ILE	432	LEU	1.283	1.630	-0.347	0.347
395	VAL	396	PRO	0.851	0.507	0.344	0.344
101	TRP	178	CYS	1.840	2.183	-0.343	0.343
43	ASN	68	ALA	5.726	5.383	0.343	0.343
102	LEU	404	TYR	0.334	0.000	0.334	0.334
173	VAL	177	GLN	0.341	0.008	0.333	0.333
265	ALA	266	PRO	0.482	0.153	0.329	0.329
49	SER	428	THR	3.119	3.447	-0.329	0.329
193	ALA	198	TYR	3.955	3.627	0.328	0.328
91	TRP	98	CYS	6.460	6.787	-0.327	0.327
70	ALA	115	ASN	0.327	0.000	0.327	0.327
195	ALA	200	PRO	1.862	2.186	-0.323	0.323
394	CYS	395	VAL	0.756	0.433	0.322	0.322
378	TRP	382	ASN	0.587	0.905	-0.318	0.318
375	ILE	380	PRO	0.381	0.064	0.317	0.317
295	GLU	296	PRO	4.551	4.865	-0.314	0.314
248	ALA	249	GLU	0.313	0.000	0.313	0.313
67	LEU	119	ILE	0.735	0.423	0.312	0.312
70	ALA	111	ALA	0.334	0.022	0.312	0.312
157	TRP	192	THR	2.317	2.005	0.311	0.311
77	PHE	101	TRP	0.311	0.000	0.311	0.311
46	VAL	68	ALA	0.962	1.272	-0.310	0.310
39	THR	411	SER	1.774	2.083	-0.310	0.310
40	VAL	75	GLY	1.483	1.791	-0.307	0.307
127	VAL	211	ILE	0.414	0.112	0.302	0.302
56	LEU	422	ASN	0.549	0.247	0.302	0.302
110	ASN	157	TRP	5.542	5.840	-0.299	0.299
218	ARG	221	GLU	0.000	0.296	-0.296	0.296
79	MET	412	THR	0.317	0.612	-0.296	0.296
61	ASN	64	LEU	0.488	0.783	-0.295	0.295
82	TYR	400	TRP	0.320	0.612	-0.292	0.292
319	PRO	320	ARG	0.292	0.000	0.292	0.292
413	ILE	416	MET	0.871	0.580	0.292	0.292
67	LEU	414	ASN	1.396	1.686	-0.289	0.289
23	TRP	24	GLN	6.355	6.642	-0.287	0.287
225	LEU	269	LEU	0.287	0.000	0.287	0.287
183	LEU	192	THR	0.000	0.285	-0.285	0.285
230	THR	231	PRO	0.141	0.424	-0.283	0.283
445	ILE	446	PRO	0.772	1.053	-0.282	0.282
291	SER	292	GLU	0.586	0.306	0.281	0.281
116	LEU	410	ASN	0.280	0.000	0.280	0.280
106	TYR	183	LEU	0.000	0.280	-0.280	0.280
42	GLY	429	PHE	0.650	0.371	0.278	0.278
157	TRP	182	PHE	1.018	1.294	-0.276	0.276
98	CYS	179	TYR	0.032	0.305	-0.274	0.274
67	LEU	71	ASP	2.081	2.352	-0.272	0.272
103	ALA	162	LEU	0.752	0.480	0.271	0.271
366	THR	417	CYS	0.000	0.270	-0.270	0.270
16	LEU	25	VAL	0.345	0.076	0.269	0.269
427	ASP	430	ARG	0.533	0.265	0.268	0.268
321	SER	322	SER	0.841	1.108	-0.267	0.267
373	ALA	413	ILE	0.499	0.764	-0.265	0.265
36	SER	40	VAL	0.265	0.000	0.265	0.265
121	PHE	203	VAL	1.340	1.078	0.262	0.262
46	VAL	425	PHE	1.266	1.006	0.260	0.260
130	PRO	218	ARG	0.410	0.151	0.259	0.259
255	PRO	256	PRO	0.658	0.916	-0.258	0.258
278	GLU	351	LYS	0.000	0.256	-0.256	0.256
300	VAL	302	ILE	0.877	0.622	0.255	0.255
39	THR	71	ASP	0.653	0.900	-0.247	0.247
41	THR	45	LEU	0.583	0.338	0.246	0.246
242	GLU	243	ARG	0.246	0.000	0.246	0.246
422	ASN	425	PHE	2.507	2.752	-0.246	0.246
184	SER	185	GLN	0.244	0.000	0.244	0.244
108	ALA	150	TRP	0.000	0.243	-0.243	0.243
204	MET	208	TYR	0.243	0.000	0.243	0.243
117	LEU	121	PHE	2.093	1.853	0.240	0.240
100	LEU	162	LEU	0.911	0.672	0.239	0.239
355	PHE	448	ARG	0.000	0.238	-0.238	0.238
58	THR	61	ASN	3.297	3.061	0.236	0.236
44	LEU	47	LEU	0.235	0.000	0.235	0.235
103	ALA	158	ALA	0.319	0.553	-0.234	0.234
73	ILE	150	TRP	0.828	0.597	0.231	0.231
205	CYS	375	ILE	0.433	0.664	-0.231	0.231
71	ASP	74	ILE	0.310	0.081	0.229	0.229
58	THR	60	ASN	0.734	0.962	-0.227	0.227
420	LEU	421	CYS	0.000	0.227	-0.227	0.227
414	ASN	419	ALA	0.225	0.000	0.225	0.225
388	SER	389	THR	0.225	0.000	0.225	0.225
19	GLY	24	GLN	0.405	0.629	-0.224	0.224
35	LEU	405	TRP	0.237	0.015	0.222	0.222
40	VAL	44	LEU	1.039	0.817	0.222	0.222
69	CYS	150	TRP	0.550	0.329	0.221	0.221
185	GLN	389	THR	0.220	0.000	0.220	0.220
157	TRP	180	ILE	0.741	0.523	0.218	0.218
448	ARG	449	PRO	0.325	0.543	-0.218	0.218
440	ARG	443	ARG	0.000	0.217	-0.217	0.217
387	VAL	395	VAL	0.552	0.337	0.215	0.215
281	ASP	423	LYS	0.000	0.214	-0.214	0.214
198	TYR	383	ILE	1.903	2.117	-0.214	0.214
167	LEU	168	VAL	0.213	0.000	0.213	0.213
99	ASP	165	GLN	3.282	3.069	0.213	0.213
17	ALA	86	LEU	0.328	0.116	0.211	0.211
120	SER	207	LEU	1.532	1.743	-0.211	0.211
63	PHE	119	ILE	1.592	1.801	-0.210	0.210
384	MET	399	LEU	3.842	3.636	0.206	0.206
215	THR	357	LEU	0.000	0.205	-0.205	0.205
93	LEU	97	ALA	0.440	0.645	-0.204	0.204
173	VAL	178	CYS	0.218	0.420	-0.202	0.202
52	VAL	432	LEU	0.299	0.097	0.202	0.202
154	PHE	159	PRO	1.890	2.090	-0.200	0.200
362	LYS	366	THR	0.200	0.000	0.200	0.200
377	THR	409	VAL	0.000	0.199	-0.199	0.199
184	SER	189	THR	0.000	0.198	-0.198	0.198
121	PHE	207	LEU	4.583	4.780	-0.198	0.198
124	TYR	125	PHE	2.260	2.456	-0.197	0.197
370	ILE	421	CYS	0.196	0.000	0.196	0.196
54	THR	55	GLU	0.000	0.196	-0.196	0.196
70	ALA	112	SER	1.267	1.071	0.196	0.196
27	PHE	31	THR	2.119	2.315	-0.196	0.196
111	ALA	153	SER	4.102	3.908	0.194	0.194
226	GLN	350	ALA	0.000	0.189	-0.189	0.189
159	PRO	163	PHE	0.746	0.557	0.189	0.189
425	PHE	429	PHE	0.588	0.777	-0.189	0.189
369	ALA	417	CYS	0.000	0.186	-0.186	0.186
74	ILE	105	ASP	0.209	0.392	-0.182	0.182
115	ASN	149	ALA	0.182	0.000	0.182	0.182
385	VAL	389	THR	0.180	0.000	0.180	0.180
262	CYS	263	CYS	0.000	0.179	-0.179	0.179
273	SER	275	LYS	0.177	0.000	0.177	0.177
381	TYR	407	CYS	1.663	1.840	-0.177	0.177
62	TYR	142	ALA	0.000	0.173	-0.173	0.173
17	ALA	20	LYS	0.021	0.191	-0.171	0.171
372	LEU	376	LEU	1.802	1.632	0.170	0.170
313	ALA	314	PRO	0.441	0.271	0.170	0.170
416	MET	421	CYS	0.169	0.000	0.169	0.169
201	VAL	375	ILE	0.229	0.398	-0.169	0.169
189	THR	385	VAL	0.979	1.146	-0.167	0.167
183	LEU	400	TRP	0.165	0.000	0.165	0.165
302	ILE	304	MET	0.000	0.164	-0.164	0.164
107	VAL	158	ALA	1.330	1.166	0.164	0.164
357	LEU	360	GLU	0.000	0.162	-0.162	0.162
130	PRO	134	ARG	0.000	0.161	-0.161	0.161
39	THR	75	GLY	1.374	1.213	0.161	0.161
85	TYR	90	HIS	4.328	4.169	0.159	0.159
123	ARG	363	ALA	0.000	0.158	-0.158	0.158
83	THR	87	LEU	1.013	1.169	-0.156	0.156
373	ALA	417	CYS	0.155	0.000	0.155	0.155
114	MET	200	PRO	0.154	0.000	0.154	0.154
79	MET	409	VAL	0.000	0.153	-0.153	0.153
117	LEU	204	MET	2.204	2.356	-0.152	0.152
50	PHE	425	PHE	0.151	0.000	0.151	0.151
151	LEU	155	VAL	0.681	0.533	0.148	0.148
390	PHE	391	CYS	0.148	0.000	0.148	0.148
172	THR	173	VAL	0.148	0.000	0.148	0.148
124	TYR	207	LEU	3.338	3.190	0.148	0.148
127	VAL	215	THR	0.078	0.225	-0.148	0.148
308	ASP	309	PRO	0.485	0.338	0.147	0.147
395	VAL	399	LEU	0.525	0.379	0.147	0.147
113	VAL	196	ALA	0.675	0.534	0.142	0.142
127	VAL	214	GLU	0.940	1.081	-0.141	0.141
431	LEU	437	TRP	5.384	5.525	-0.141	0.141
90	HIS	92	ALA	0.782	0.923	-0.141	0.141
113	VAL	200	PRO	0.657	0.795	-0.138	0.138
117	LEU	203	VAL	1.149	1.012	0.137	0.137
442	TRP	447	LYS	0.000	0.136	-0.136	0.136
46	VAL	64	LEU	0.186	0.321	-0.136	0.136
120	SER	211	ILE	0.320	0.453	-0.133	0.133
85	TYR	86	LEU	0.565	0.436	0.129	0.129
164	TRP	188	ILE	1.533	1.405	0.128	0.128
102	LEU	106	TYR	0.370	0.243	0.127	0.127
194	MET	199	LEU	3.044	3.171	-0.127	0.127
59	VAL	63	PHE	0.000	0.127	-0.127	0.127
15	VAL	88	MET	1.126	1.000	0.126	0.126
456	PRO	457	SER	0.126	0.000	0.126	0.126
168	VAL	181	GLN	0.000	0.125	-0.125	0.125
119	ILE	208	TYR	0.210	0.085	0.125	0.125
218	ARG	360	GLU	0.245	0.370	-0.125	0.125
398	THR	402	LEU	0.086	0.211	-0.125	0.125
13	ILE	15	VAL	0.578	0.453	0.125	0.125
138	THR	141	ARG	2.206	2.082	0.124	0.124
98	CYS	102	LEU	0.914	0.790	0.124	0.124
239	SER	240	SER	0.000	0.123	-0.123	0.123
53	ASN	424	ALA	0.332	0.455	-0.123	0.123
185	GLN	186	PRO	0.445	0.322	0.123	0.123
207	LEU	208	TYR	0.000	0.123	-0.123	0.123
379	THR	383	ILE	1.387	1.265	0.123	0.123
387	VAL	394	CYS	0.962	0.843	0.119	0.119
64	LEU	119	ILE	0.763	0.646	0.117	0.117
200	PRO	204	MET	0.000	0.115	-0.115	0.115
72	LEU	76	THR	1.089	1.201	-0.112	0.112
163	PHE	166	TYR	0.193	0.082	0.110	0.110
377	THR	413	ILE	0.476	0.366	0.110	0.110
78	SER	101	TRP	2.054	2.162	-0.108	0.108
46	VAL	415	PRO	0.354	0.462	-0.108	0.108
70	ALA	150	TRP	3.273	3.166	0.107	0.107
50	PHE	58	THR	0.201	0.308	-0.107	0.107
126	SER	137	ARG	1.008	0.902	0.106	0.106
203	VAL	207	LEU	0.982	0.879	0.103	0.103
432	LEU	437	TRP	1.274	1.173	0.101	0.101
260	CYS	263	CYS	0.100	0.000	0.100	0.100
105	ASP	106	TYR	0.015	0.115	-0.100	0.100
128	THR	214	GLU	0.208	0.307	-0.099	0.099
193	ALA	386	LEU	0.421	0.322	0.099	0.099
168	VAL	170	GLU	0.180	0.081	0.099	0.099
73	ILE	108	ALA	0.749	0.847	-0.098	0.098
428	THR	432	LEU	0.757	0.660	0.097	0.097
105	ASP	109	SER	0.737	0.641	0.096	0.096
39	THR	43	ASN	0.771	0.677	0.094	0.094
78	SER	105	ASP	6.688	6.781	-0.092	0.092
180	ILE	182	PHE	4.140	4.049	0.091	0.091
73	ILE	78	SER	0.959	0.868	0.091	0.091
400	TRP	404	TYR	0.090	0.000	0.090	0.090
123	ARG	137	ARG	0.000	0.088	-0.088	0.088
111	ALA	115	ASN	0.072	0.160	-0.087	0.087
366	THR	370	ILE	0.476	0.389	0.087	0.087
74	ILE	112	SER	0.087	0.000	0.087	0.087
304	MET	305	PRO	0.525	0.439	0.086	0.086
43	ASN	71	ASP	4.230	4.316	-0.086	0.086
199	LEU	200	PRO	1.329	1.415	-0.086	0.086
74	ILE	408	TYR	1.484	1.399	0.085	0.085
294	GLU	295	GLU	0.000	0.083	-0.083	0.083
99	ASP	162	LEU	1.499	1.582	-0.083	0.083
17	ALA	87	LEU	0.000	0.082	-0.082	0.082
125	PHE	128	THR	0.077	0.159	-0.082	0.082
54	THR	447	LYS	0.000	0.081	-0.081	0.081
410	ASN	413	ILE	0.079	0.000	0.079	0.079
74	ILE	109	SER	2.119	2.041	0.078	0.078
211	ILE	364	ALA	0.000	0.076	-0.076	0.076
374	PHE	379	THR	0.000	0.073	-0.073	0.073
30	ILE	34	LEU	0.482	0.554	-0.073	0.073
116	LEU	119	ILE	0.095	0.024	0.072	0.072
438	ASP	439	LYS	0.171	0.100	0.071	0.071
114	MET	152	VAL	0.279	0.349	-0.070	0.070
64	LEU	425	PHE	0.328	0.397	-0.069	0.069
212	TYR	215	THR	0.157	0.089	0.068	0.068
287	SER	289	THR	0.000	0.068	-0.068	0.068
31	THR	35	LEU	0.084	0.151	-0.067	0.067
23	TRP	27	PHE	0.067	0.000	0.067	0.067
124	TYR	129	ARG	0.023	0.089	-0.066	0.066
124	TYR	211	ILE	3.307	3.242	0.066	0.066
36	SER	79	MET	1.791	1.725	0.066	0.066
79	MET	80	ASN	0.000	0.063	-0.063	0.063
10	SER	11	PRO	0.386	0.448	-0.061	0.061
157	TRP	161	ILE	0.587	0.647	-0.061	0.061
366	THR	367	LEU	0.000	0.060	-0.060	0.060
59	VAL	139	PRO	2.099	2.039	0.060	0.060
422	ASN	424	ALA	0.909	0.968	-0.059	0.059
214	GLU	217	ASN	0.028	0.087	-0.059	0.059
40	VAL	76	THR	1.847	1.906	-0.059	0.059
329	PRO	330	THR	2.379	2.437	-0.058	0.058
384	MET	400	TRP	5.536	5.478	0.058	0.058
174	LEU	177	GLN	2.798	2.741	0.057	0.057
374	PHE	375	ILE	0.069	0.125	-0.055	0.055
173	VAL	181	GLN	1.373	1.319	0.054	0.054
53	ASN	54	THR	0.045	0.099	-0.054	0.054
46	VAL	65	LEU	0.000	0.053	-0.053	0.053
317	GLN	318	PRO	1.566	1.513	0.053	0.053
192	THR	197	PHE	0.067	0.118	-0.051	0.051
379	THR	380	PRO	0.923	0.974	-0.050	0.050
388	SER	395	VAL	0.049	0.000	0.049	0.049
426	ARG	430	ARG	0.797	0.749	0.048	0.048
165	GLN	166	TYR	3.408	3.362	0.046	0.046
194	MET	200	PRO	0.189	0.143	0.045	0.045
115	ASN	118	LEU	0.000	0.045	-0.045	0.045
35	LEU	412	THR	0.913	0.868	0.044	0.044
63	PHE	137	ARG	0.044	0.000	0.044	0.044
154	PHE	158	ALA	1.755	1.797	-0.043	0.043
154	PHE	155	VAL	0.185	0.227	-0.042	0.042
299	GLU	300	VAL	0.000	0.042	-0.042	0.042
271	ALA	272	TYR	0.041	0.000	0.041	0.041
326	VAL	327	LYS	0.000	0.041	-0.041	0.041
377	THR	378	TRP	1.573	1.611	-0.038	0.038
79	MET	411	SER	0.000	0.038	-0.038	0.038
62	TYR	146	ILE	2.026	1.988	0.038	0.038
383	ILE	387	VAL	0.228	0.265	-0.037	0.037
201	VAL	205	CYS	0.322	0.358	-0.036	0.036
158	ALA	162	LEU	0.032	0.067	-0.036	0.036
202	THR	206	THR	0.085	0.121	-0.035	0.035
356	SER	357	LEU	0.035	0.000	0.035	0.035
73	ILE	104	LEU	1.459	1.494	-0.035	0.035
44	LEU	72	LEU	1.509	1.543	-0.034	0.034
54	THR	57	LYS	0.111	0.077	0.034	0.034
381	TYR	384	MET	0.000	0.033	-0.033	0.033
188	ILE	192	THR	0.438	0.406	0.033	0.033
162	LEU	163	PHE	0.112	0.080	0.032	0.032
102	LEU	178	CYS	1.548	1.580	-0.032	0.032
28	ILE	33	GLY	0.000	0.032	-0.032	0.032
431	LEU	438	ASP	0.000	0.030	-0.030	0.030
6	PRO	7	PRO	0.710	0.681	0.029	0.029
49	SER	425	PHE	1.148	1.177	-0.029	0.029
315	THR	316	LYS	0.000	0.029	-0.029	0.029
365	ARG	368	SER	0.070	0.042	0.028	0.028
112	SER	411	SER	0.028	0.000	0.028	0.028
112	SER	410	ASN	0.188	0.216	-0.028	0.028
81	LEU	91	TRP	1.451	1.424	0.026	0.026
29	GLY	83	THR	0.124	0.150	-0.026	0.026
123	ARG	211	ILE	1.569	1.594	-0.025	0.025
377	THR	403	GLY	0.038	0.014	0.025	0.025
38	ALA	412	THR	0.582	0.558	0.024	0.024
414	ASN	415	PRO	0.894	0.917	-0.023	0.023
452	VAL	454	ARG	0.022	0.000	0.022	0.022
199	LEU	203	VAL	0.401	0.379	0.022	0.022
138	THR	140	ARG	0.356	0.335	0.021	0.021
89	GLY	176	GLY	0.020	0.000	0.020	0.020
120	SER	371	LEU	0.000	0.020	-0.020	0.020
193	ALA	382	ASN	0.033	0.053	-0.020	0.020
409	VAL	412	THR	0.000	0.019	-0.019	0.019
159	PRO	164	TRP	0.301	0.282	0.019	0.019
129	ARG	130	PRO	0.113	0.096	0.018	0.018
158	ALA	159	PRO	0.828	0.811	0.017	0.017
17	ALA	18	PRO	0.474	0.456	0.017	0.017
130	PRO	131	LEU	0.000	0.016	-0.016	0.016
103	ALA	161	ILE	2.563	2.579	-0.016	0.016
11	PRO	12	ASN	0.015	0.000	0.015	0.015
211	ILE	215	THR	0.085	0.070	0.015	0.015
64	LEU	419	ALA	0.014	0.000	0.014	0.014
52	VAL	428	THR	0.361	0.347	0.014	0.014
52	VAL	53	ASN	0.084	0.071	0.013	0.013
98	CYS	177	GLN	0.076	0.089	-0.013	0.013
121	PHE	126	SER	0.000	0.013	-0.013	0.013
105	ASP	408	TYR	5.717	5.705	0.012	0.012
153	SER	158	ALA	0.033	0.045	-0.011	0.011
116	LEU	208	TYR	0.010	0.000	0.010	0.010
138	THR	139	PRO	0.909	0.900	0.009	0.009
59	VAL	142	ALA	0.886	0.895	-0.009	0.009
48	ILE	52	VAL	0.404	0.413	-0.009	0.009
73	ILE	77	PHE	0.315	0.307	0.008	0.008
201	VAL	204	MET	0.000	0.007	-0.007	0.007
367	LEU	370	ILE	0.000	0.007	-0.007	0.007
279	GLU	448	ARG	0.000	0.007	-0.007	0.007
399	LEU	402	LEU	0.111	0.117	-0.007	0.007
55	GLU	442	TRP	0.259	0.253	0.006	0.006
37	LEU	41	THR	0.864	0.858	0.006	0.006
28	ILE	32	THR	0.348	0.353	-0.005	0.005
5	ALA	6	PRO	0.635	0.631	0.004	0.004
44	LEU	48	ILE	0.061	0.058	0.002	0.002
83	THR	405	TRP	2.666	2.668	-0.002	0.002
47	LEU	72	LEU	0.675	0.674	0.001	0.001
85	TYR	91	TRP	4.627	4.627	0.001	0.001

RRCS change distribution

-0.12

Mean ΔRRCS

1.39

Std Dev

-0.03

Median

Magnitude classification

High (|Δ| ≥ 5.0)

Medium (2.0 ≤ |Δ| < 5.0)

623

Low (|Δ| < 2.0)

Methods

RRCS analysis. Residue-Residue Contact Scores (RRCS) were calculated for each conformational state based on inter-atomic distances. Changes (ΔRRCS) were computed by comparing active and inactive structures predicted by AlphaFold multistate (del Alamo et al., 2022).

Significance threshold. |ΔRRCS| ≥ 1.96, 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