Aggrescan3D: survivor [mutate: IC23D, IC52D, FC87D, IC120K]

Project name: survivor [mutate: IC23D, IC52D, FC87D, IC120K]

Status: done

submitted: 2019-10-10 02:59:46, status changed: 2019-10-10 05:25:22

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Chain sequence(s)	C: LKFNQLKFRKKKLKFCKSHIHDWGLFAMEPIAADEMVIEYVGQNIRQVIADMREKRYEDEGIGSSYMFRVDHDTIIDATKCGNFARFINHSCNPNCYAKVITVESQKKIVIYSKQHINVNEEITYDYKFPIEDVKIPCLCGSENCRGTLN
Distance of aggregation	10 Å
Dynamic mode	Yes
Mutated residues	IC23D, IC52D, FC87D, IC120K
Energy difference between WT (input) and mutated protein (by FoldX)	-0.725679 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: -4.2156
Maximal score value: 0.9611
Average score: -1.0739
Total score value: -161.0866

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	0.2701
5	K	C	-1.3151
6	F	C	-0.6687
7	N	C	-1.2587
8	Q	C	-1.5928
9	L	C	0.0000
10	K	C	-1.4019
11	F	C	-0.4761
12	R	C	-2.0335
13	K	C	0.0000
14	K	C	-2.7433
15	K	C	-2.4545
16	L	C	-1.0777
17	K	C	-0.7859
18	F	C	0.8876
19	C	C	0.7347
20	K	C	-1.1014
21	S	C	-1.6127
22	H	C	-2.4502
23	D	C	-2.6835	mutated: IC23D
24	H	C	-2.1010
25	D	C	-1.6545
26	W	C	0.0000
27	G	C	-0.2658
28	L	C	0.0000
29	F	C	-0.5171
30	A	C	0.0000
31	M	C	-1.4955
32	E	C	-1.8644
33	P	C	-1.6713
34	I	C	0.0000
35	A	C	-1.7489
36	A	C	-1.6892
37	D	C	-2.2098
38	E	C	-1.7546
39	M	C	-0.4503
40	V	C	0.0000
41	I	C	0.0000
42	E	C	0.0000
43	Y	C	-0.4676
44	V	C	0.0000
45	G	C	-1.3575
46	Q	C	-1.6974
47	N	C	-2.2708
48	I	C	-2.0637
49	R	C	-2.7977
50	Q	C	-1.5145
51	V	C	0.5292
52	D	C	-0.7332	mutated: IC52D
53	A	C	0.0000
54	D	C	-1.1128
55	M	C	-0.8811
56	R	C	-1.7084
57	E	C	-2.6359
58	K	C	-4.0066
59	R	C	-3.7378
60	Y	C	-2.8453
61	E	C	-3.9731
62	D	C	-4.2156
63	E	C	-3.4556
64	G	C	-1.9645
65	I	C	0.2531
66	G	C	-0.0374
67	S	C	-0.4834
68	S	C	-0.5899
69	Y	C	0.0000
70	M	C	-0.0983
71	F	C	0.0000
72	R	C	-1.2287
73	V	C	-0.9335
74	D	C	-1.9034
75	H	C	-2.1957
76	D	C	-2.4978
77	T	C	-2.2854
78	I	C	0.0000
79	I	C	0.0000
80	D	C	0.0000
81	A	C	0.0000
82	T	C	-1.0728
83	K	C	-1.7796
84	C	C	-1.4130
85	G	C	-1.6332
86	N	C	-2.2790
87	D	C	-2.2460	mutated: FC87D
88	A	C	0.0000
89	R	C	-0.8142
90	F	C	0.0000
91	I	C	0.0000
92	N	C	-0.9114
93	H	C	-0.8358
94	S	C	-0.7566
95	C	C	-0.6775
96	N	C	-0.7307
97	P	C	-0.6420
98	N	C	-1.1722
99	C	C	0.0000
100	Y	C	-0.3605
101	A	C	0.0000
102	K	C	-0.6000
103	V	C	0.0000
104	I	C	0.1843
105	T	C	-0.4259
106	V	C	-0.3820
107	E	C	-1.8999
108	S	C	-0.9692
109	Q	C	-0.8434
110	K	C	-0.7304
111	K	C	-0.2733
112	I	C	0.0000
113	V	C	0.0000
114	I	C	0.0000
115	Y	C	-0.5215
116	S	C	0.0000
117	K	C	-2.8211
118	Q	C	-2.8359
119	H	C	-2.1079
120	K	C	-2.4301	mutated: IC120K
121	N	C	-1.2427
122	V	C	0.1096
123	N	C	-1.1787
124	E	C	0.0000
125	E	C	-1.8366
126	I	C	0.0000
127	T	C	-0.7975
128	Y	C	0.0000
129	D	C	-0.8580
130	Y	C	0.0000
131	K	C	-0.7971
132	F	C	-0.7407
133	P	C	-0.8859
134	I	C	-1.2804
135	E	C	-2.5128
136	D	C	-2.6787
137	V	C	-1.6067
138	K	C	-2.3568
139	I	C	-1.0092
140	P	C	-0.5086
141	C	C	0.1336
142	L	C	0.9611
143	C	C	0.1855
144	G	C	-1.2835
145	S	C	-1.7230
146	E	C	-2.8329
147	N	C	-2.4038
148	C	C	-1.7914
149	R	C	-2.0695
150	G	C	0.0000
151	T	C	-0.4454
152	L	C	0.0000
153	N	C	-1.5594

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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, -1.0739 in this case) is selected and presented in A3D results.