Aggrescan3D: survivor [mutate: IC52D, IC23D]

Project name: survivor [mutate: IC52D, IC23D]

Status: done

submitted: 2019-10-11 13:43:21, status changed: 2019-10-11 16:11:41

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Chain sequence(s)	C: LKFNQLKFRKKKLKFCKSHIHDWGLFAMEPIAADEMVIEYVGQNIRQVIADMREKRYEDEGIGSSYMFRVDHDTIIDATKCGNFARFINHSCNPNCYAKVITVESQKKIVIYSKQHINVNEEITYDYKFPIEDVKIPCLCGSENCRGTLN
Distance of aggregation	10 Å
Dynamic mode	Yes
Mutated residues	IC52D, IC23D
Energy difference between WT (input) and mutated protein (by FoldX)	0.55003 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: -4.3137
Maximal score value: 1.2973
Average score: -0.8417
Total score value: -126.2502

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	0.4762
5	K	C	-1.2177
6	F	C	-0.5734
7	N	C	-0.2942
8	Q	C	-1.0310
9	L	C	-0.5932
10	K	C	0.0000
11	F	C	0.1415
12	R	C	-0.9833
13	K	C	0.0000
14	K	C	-2.4130
15	K	C	-2.5811
16	L	C	-1.7937
17	K	C	-1.9575
18	F	C	-0.2354
19	C	C	-0.4267
20	K	C	-2.3368
21	S	C	-2.1271
22	H	C	-2.8905
23	D	C	-3.2389	mutated: IC23D
24	H	C	-2.7833
25	D	C	-2.4423
26	W	C	0.0000
27	G	C	-0.9825
28	L	C	0.0000
29	F	C	-0.8174
30	A	C	0.0000
31	M	C	-1.1142
32	E	C	-0.6395
33	P	C	0.7166
34	I	C	0.9545
35	A	C	-0.0740
36	A	C	-0.8707
37	D	C	-2.0276
38	E	C	0.0000
39	M	C	-0.3336
40	V	C	0.0000
41	I	C	0.0000
42	E	C	0.2097
43	Y	C	0.9614
44	V	C	0.4648
45	G	C	-0.7232
46	Q	C	-1.7736
47	N	C	-2.2482
48	I	C	0.0000
49	R	C	-1.9891
50	Q	C	-1.1060
51	V	C	0.2053
52	D	C	-1.7377	mutated: IC52D
53	A	C	0.0000
54	D	C	-2.4515
55	M	C	-1.5346
56	R	C	-2.3327
57	E	C	-3.2561
58	K	C	-4.3137
59	R	C	-4.0153
60	Y	C	-2.6518
61	E	C	-3.9295
62	D	C	-4.0805
63	E	C	-2.7363
64	G	C	-0.9717
65	I	C	0.5259
66	G	C	-0.1384
67	S	C	-0.2266
68	S	C	-0.2678
69	Y	C	-0.0924
70	M	C	0.2194
71	F	C	0.0000
72	R	C	-1.4497
73	V	C	-0.9843
74	D	C	-1.3734
75	H	C	-1.7596
76	D	C	-2.1009
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	-0.8959
83	K	C	-1.9219
84	C	C	-0.9083
85	G	C	-1.2089
86	N	C	-1.4243
87	F	C	-0.1332
88	A	C	0.0000
89	R	C	-0.4337
90	F	C	0.0000
91	I	C	0.0000
92	N	C	-1.4865
93	H	C	-0.8721
94	S	C	0.0000
95	C	C	-1.1264
96	N	C	-1.8415
97	P	C	-1.4777
98	N	C	-1.7327
99	C	C	0.0000
100	Y	C	-0.3967
101	A	C	0.0000
102	K	C	-0.3431
103	V	C	0.0000
104	I	C	0.7134
105	T	C	0.4159
106	V	C	0.6198
107	E	C	-1.4194
108	S	C	-1.6050
109	Q	C	-1.4936
110	K	C	-0.7488
111	K	C	-0.2680
112	I	C	0.0000
113	V	C	0.0000
114	I	C	0.0000
115	Y	C	-0.5800
116	S	C	0.0000
117	K	C	-1.4212
118	Q	C	-1.3715
119	H	C	-0.2988
120	I	C	1.1899
121	N	C	0.1428
122	V	C	1.1735
123	N	C	-0.4494
124	E	C	0.0000
125	E	C	-2.0167
126	I	C	0.0000
127	T	C	-0.8960
128	Y	C	0.0000
129	D	C	0.0000
130	Y	C	0.0000
131	K	C	-0.2951
132	F	C	-0.4448
133	P	C	-0.8843
134	I	C	-0.7627
135	E	C	-2.3733
136	D	C	-2.4624
137	V	C	-0.9318
138	K	C	-1.5737
139	I	C	-0.2750
140	P	C	0.2801
141	C	C	0.8479
142	L	C	1.2973
143	C	C	0.2486
144	G	C	-1.2236
145	S	C	-1.8718
146	E	C	-2.9297
147	N	C	-2.5964
148	C	C	-2.2267
149	R	C	-2.3327
150	G	C	0.0000
151	T	C	0.1757
152	L	C	0.4768
153	N	C	0.2713

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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, -0.8417 in this case) is selected and presented in A3D results.