Aggrescan3D: survivor [mutate: IC23R]

Project name: survivor [mutate: IC23R]

Status: done

submitted: 2019-10-11 12:42:08, status changed: 2019-10-11 15:10:18

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Chain sequence(s)	C: LKFNQLKFRKKKLKFCKSHIHDWGLFAMEPIAADEMVIEYVGQNIRQVIADMREKRYEDEGIGSSYMFRVDHDTIIDATKCGNFARFINHSCNPNCYAKVITVESQKKIVIYSKQHINVNEEITYDYKFPIEDVKIPCLCGSENCRGTLN
Distance of aggregation	10 Å
Dynamic mode	Yes
Mutated residues	IC23R
Energy difference between WT (input) and mutated protein (by FoldX)	0.00784139 kcal/mol Changes in protein stability upon mutation are calculated using the FoldX forcefield. Computational prediction of protein stability is used with the intention of preventing the experimental characterization of proteins bearing mutations that significantly destabilize their structure. Mutations resulting in a predicted reduction in protein stability ≥ 1 kcal/mol are considered disruptive.

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Minimal score value: -4.4572
Maximal score value: 1.9616
Average score: -0.8744
Total score value: -131.1658

The table below lists A3D score for protein residues. Residues with A3D score > 0.0000 are marked by yellow rows.

residue index	residue name	chain	Aggrescan3D score	mutation
residue index	residue name	chain	Aggrescan3D score	mutation
4	L	C	0.3038
5	K	C	-1.1023
6	F	C	-0.1144
7	N	C	-1.4179
8	Q	C	-1.7621
9	L	C	-1.4042
10	K	C	-1.9807
11	F	C	-0.5576
12	R	C	-2.0574
13	K	C	-2.1762
14	K	C	-2.6502
15	K	C	-1.9463
16	L	C	0.0000
17	K	C	-1.0274
18	F	C	0.3733
19	C	C	-0.5602
20	K	C	-2.0494
21	S	C	-1.6337
22	H	C	-2.3443
23	R	C	-2.5675	mutated: IC23R
24	H	C	-1.4473
25	D	C	0.0000
26	W	C	0.0000
27	G	C	0.0000
28	L	C	0.0000
29	F	C	0.7786
30	A	C	0.0000
31	M	C	0.0000
32	E	C	-1.4072
33	P	C	-0.3702
34	I	C	0.0000
35	A	C	-0.3285
36	A	C	-1.0188
37	D	C	-2.2002
38	E	C	0.0000
39	M	C	-0.0104
40	V	C	0.0000
41	I	C	0.0000
42	E	C	-1.1536
43	Y	C	0.0000
44	V	C	-0.3993
45	G	C	0.0000
46	Q	C	-1.4460
47	N	C	-1.4013
48	I	C	-0.9289
49	R	C	-1.3928
50	Q	C	-0.4246
51	V	C	1.6455
52	I	C	1.9616
53	A	C	0.0000
54	D	C	-0.5400
55	M	C	-0.0476
56	R	C	-1.0508
57	E	C	-2.6742
58	K	C	-4.0848
59	R	C	-4.4572
60	Y	C	-3.4506
61	E	C	-4.1184
62	D	C	-4.3918
63	E	C	-3.7152
64	G	C	-1.6583
65	I	C	0.5554
66	G	C	-0.0829
67	S	C	-0.1053
68	S	C	-0.3148
69	Y	C	-0.1654
70	M	C	-0.1946
71	F	C	0.0000
72	R	C	-1.8984
73	V	C	0.0000
74	D	C	-2.8432
75	H	C	-2.4742
76	D	C	-2.8665
77	T	C	0.0000
78	I	C	0.0000
79	I	C	0.0000
80	D	C	0.0000
81	A	C	0.0000
82	T	C	-1.1418
83	K	C	-1.9322
84	C	C	-1.1908
85	G	C	-1.3271
86	N	C	-1.8105
87	F	C	0.0000
88	A	C	-1.2943
89	R	C	-1.0075
90	F	C	0.0000
91	I	C	0.0000
92	N	C	0.0000
93	H	C	-0.2677
94	S	C	0.0000
95	C	C	-1.2968
96	N	C	-1.4230
97	P	C	-1.5053
98	N	C	-1.8404
99	C	C	0.0000
100	Y	C	-0.5803
101	A	C	0.0000
102	K	C	-0.2514
103	V	C	0.0000
104	I	C	1.2356
105	T	C	0.2998
106	V	C	0.9121
107	E	C	-1.1294
108	S	C	-1.5180
109	Q	C	-0.9964
110	K	C	0.0000
111	K	C	-0.5803
112	I	C	0.0000
113	V	C	0.1539
114	I	C	0.0000
115	Y	C	-0.3419
116	S	C	0.0000
117	K	C	-2.4290
118	Q	C	-1.9250
119	H	C	-1.0044
120	I	C	0.8818
121	N	C	0.0075
122	V	C	0.5234
123	N	C	-1.0769
124	E	C	-0.8995
125	E	C	-1.3062
126	I	C	0.0000
127	T	C	0.0000
128	Y	C	0.0000
129	D	C	0.0000
130	Y	C	0.0000
131	K	C	-0.8672
132	F	C	0.0000
133	P	C	-0.8004
134	I	C	-1.1604
135	E	C	-2.3889
136	D	C	-2.9468
137	V	C	-1.9693
138	K	C	-2.4953
139	I	C	-1.1782
140	P	C	-0.6869
141	C	C	-0.1453
142	L	C	0.9317
143	C	C	-0.2141
144	G	C	-1.3055
145	S	C	-1.9034
146	E	C	-2.7288
147	N	C	-2.5524
148	C	C	-1.9046
149	R	C	-2.1147
150	G	C	0.0000
151	T	C	-0.6160
152	L	C	0.0000
153	N	C	-1.2604

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Above is the comparison between the input structure and the most aggregation prone model (predicted in the flexibility simulations, download both models in the PDB file format , download table with rmsd values ). The picture presents the most aggregation prone model (in blue) superimposed on the input structure (in red). The plot shows rmsd profile (distances between residues of the superimposed structures).

Dynamic mode uses CABS-flex simulations of protein structure fluctuations. The structure fluctuations may have impact on the size and extent of aggregation "hot-spots" on the protein surface. The dynamic mode uses the following pipeline: (1) based on the input structure, CABS-flex predicts a set of different models reflecting protein dynamics in solution; (2) for each of these models A3D score is calculated; (3) finally, the most aggregation prone model (the model with the highest A3D score, -0.8744 in this case) is selected and presented in A3D results.