Aggrescan3D: survivor [mutate: IC52D, IC23D, IC120K]

Project name: survivor [mutate: IC52D, IC23D, IC120K]

Status: done

submitted: 2019-10-12 04:31:36, status changed: 2019-10-12 07:00:17

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Chain sequence(s)	C: LKFNQLKFRKKKLKFCKSHIHDWGLFAMEPIAADEMVIEYVGQNIRQVIADMREKRYEDEGIGSSYMFRVDHDTIIDATKCGNFARFINHSCNPNCYAKVITVESQKKIVIYSKQHINVNEEITYDYKFPIEDVKIPCLCGSENCRGTLN
Distance of aggregation	10 Å
Dynamic mode	Yes
Mutated residues	IC52D, IC23D, IC120K
Energy difference between WT (input) and mutated protein (by FoldX)	0.220732 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: -3.8019
Maximal score value: 1.8231
Average score: -0.8756
Total score value: -131.3446

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	0.5617
5	K	C	-1.3358
6	F	C	-0.9999
7	N	C	-1.7670
8	Q	C	-1.9912
9	L	C	0.0000
10	K	C	-1.0085
11	F	C	0.3130
12	R	C	-1.3348
13	K	C	-2.3409
14	K	C	0.0000
15	K	C	-2.1195
16	L	C	0.0000
17	K	C	-1.2009
18	F	C	-0.4083
19	C	C	-0.5261
20	K	C	-1.6433
21	S	C	-1.7696
22	H	C	-2.6959
23	D	C	-2.9605	mutated: IC23D
24	H	C	-2.3563
25	D	C	-2.3800
26	W	C	0.0000
27	G	C	0.0000
28	L	C	0.0000
29	F	C	-0.7075
30	A	C	0.0000
31	M	C	-0.4244
32	E	C	-0.3002
33	P	C	0.1561
34	I	C	-0.3562
35	A	C	-1.1755
36	A	C	-1.1739
37	D	C	-1.0566
38	E	C	0.0000
39	M	C	0.0000
40	V	C	0.0000
41	I	C	0.0000
42	E	C	-0.3108
43	Y	C	0.0000
44	V	C	-0.8409
45	G	C	-1.4414
46	Q	C	-1.6349
47	N	C	-2.5621
48	I	C	0.0000
49	R	C	-2.9111
50	Q	C	-1.7470
51	V	C	-0.0486
52	D	C	-1.8414	mutated: IC52D
53	A	C	0.0000
54	D	C	-1.5362
55	M	C	-1.1052
56	R	C	-2.0526
57	E	C	-2.6136
58	K	C	-3.6653
59	R	C	-3.6345
60	Y	C	-2.8776
61	E	C	-3.8019
62	D	C	-3.7034
63	E	C	-2.4734
64	G	C	-0.9710
65	I	C	0.1880
66	G	C	-0.0402
67	S	C	0.0592
68	S	C	0.3042
69	Y	C	0.9121
70	M	C	0.6641
71	F	C	0.0000
72	R	C	-1.2012
73	V	C	0.0000
74	D	C	-2.6634
75	H	C	-2.3609
76	D	C	-2.5017
77	T	C	-2.3175
78	I	C	0.0000
79	I	C	0.0000
80	D	C	-0.8159
81	A	C	0.0000
82	T	C	-1.2360
83	K	C	-2.2160
84	C	C	0.0000
85	G	C	-1.4447
86	N	C	-1.7122
87	F	C	-1.2331
88	A	C	-1.1155
89	R	C	-0.5466
90	F	C	0.0000
91	I	C	0.1431
92	N	C	-0.4530
93	H	C	-0.1558
94	S	C	-0.4781
95	C	C	-0.5362
96	N	C	-0.9126
97	P	C	-0.8251
98	N	C	-1.1552
99	C	C	0.0000
100	Y	C	-0.2644
101	A	C	0.0000
102	K	C	-0.4209
103	V	C	0.0000
104	I	C	0.7532
105	T	C	0.3586
106	V	C	0.4519
107	E	C	-1.4281
108	S	C	-1.3666
109	Q	C	-1.3988
110	K	C	-0.8975
111	K	C	-0.4018
112	I	C	0.0000
113	V	C	0.0000
114	I	C	0.0000
115	Y	C	0.0000
116	S	C	0.0000
117	K	C	-1.7055
118	Q	C	-2.3204
119	H	C	-2.1161
120	K	C	-2.1172	mutated: IC120K
121	N	C	-1.0865
122	V	C	0.6435
123	N	C	-0.5323
124	E	C	0.0000
125	E	C	-1.6509
126	I	C	0.0000
127	T	C	-0.5675
128	Y	C	0.0000
129	D	C	-0.5641
130	Y	C	-0.4341
131	K	C	-0.6557
132	F	C	-0.4173
133	P	C	-0.4576
134	I	C	-0.9358
135	E	C	-2.5163
136	D	C	-2.5604
137	V	C	-1.4989
138	K	C	-1.4538
139	I	C	0.6538
140	P	C	0.7319
141	C	C	1.5257
142	L	C	1.8231
143	C	C	0.9945
144	G	C	-1.0181
145	S	C	-1.8434
146	E	C	-2.9446
147	N	C	-2.5183
148	C	C	-1.8447
149	R	C	-2.0491
150	G	C	0.0000
151	T	C	0.5085
152	L	C	0.6505
153	N	C	-0.0280

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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, -0.8756 in this case) is selected and presented in A3D results.