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

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

Status: done

submitted: 2019-10-07 07:44:51, status changed: 2019-10-07 19:49:11

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Chain sequence(s)	C: LKFNQLKFRKKKLKFCKSHIHDWGLFAMEPIAADEMVIEYVGQNIRQVIADMREKRYEDEGIGSSYMFRVDHDTIIDATKCGNFARFINHSCNPNCYAKVITVESQKKIVIYSKQHINVNEEITYDYKFPIEDVKIPCLCGSENCRGTLN
Distance of aggregation	10 Å
Dynamic mode	Yes
Mutated residues	IC23D, IC52D, IC120K
Energy difference between WT (input) and mutated protein (by FoldX)	0.194093 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: -3.823
Maximal score value: 1.807
Average score: -0.8747
Total score value: -131.2108

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	0.5729
5	K	C	-1.3344
6	F	C	-0.9894
7	N	C	-1.7533
8	Q	C	-1.9783
9	L	C	0.0000
10	K	C	-0.9923
11	F	C	0.3240
12	R	C	-1.2763
13	K	C	-2.3214
14	K	C	0.0000
15	K	C	-2.0984
16	L	C	0.0000
17	K	C	-1.1818
18	F	C	-0.4194
19	C	C	-0.5463
20	K	C	-1.6765
21	S	C	-1.7804
22	H	C	-2.6847
23	D	C	-2.9417	mutated: IC23D
24	H	C	-2.3192
25	D	C	-2.3339
26	W	C	0.0000
27	G	C	0.0000
28	L	C	0.0000
29	F	C	-0.6909
30	A	C	0.0000
31	M	C	-0.3664
32	E	C	-0.2864
33	P	C	0.0977
34	I	C	0.0000
35	A	C	-1.2962
36	A	C	-1.2624
37	D	C	-1.1640
38	E	C	0.0000
39	M	C	0.0000
40	V	C	0.0000
41	I	C	0.0000
42	E	C	-0.2987
43	Y	C	0.0000
44	V	C	-0.8365
45	G	C	-1.4514
46	Q	C	-1.6427
47	N	C	-2.5729
48	I	C	0.0000
49	R	C	-2.8686
50	Q	C	-1.6862
51	V	C	0.0123
52	D	C	-1.7917	mutated: IC52D
53	A	C	0.0000
54	D	C	-1.3214
55	M	C	-1.0215
56	R	C	-2.0313
57	E	C	-2.6142
58	K	C	-3.6361
59	R	C	-3.6377
60	Y	C	-2.8605
61	E	C	-3.8230
62	D	C	-3.7180
63	E	C	-2.4777
64	G	C	-0.9322
65	I	C	0.2848
66	G	C	0.0010
67	S	C	0.0595
68	S	C	0.2614
69	Y	C	0.8957
70	M	C	0.5572
71	F	C	0.0000
72	R	C	-1.1331
73	V	C	0.0000
74	D	C	-2.5733
75	H	C	-2.2881
76	D	C	-2.4370
77	T	C	-2.2819
78	I	C	0.0000
79	I	C	0.0000
80	D	C	-0.8616
81	A	C	0.0000
82	T	C	-1.2523
83	K	C	-2.2160
84	C	C	0.0000
85	G	C	-1.3939
86	N	C	-1.7104
87	F	C	-1.2250
88	A	C	-1.1058
89	R	C	-0.5299
90	F	C	0.0000
91	I	C	0.1535
92	N	C	-0.4220
93	H	C	-0.3072
94	S	C	-0.4672
95	C	C	-0.5012
96	N	C	-0.8675
97	P	C	-0.7773
98	N	C	-1.1017
99	C	C	0.0000
100	Y	C	-0.2067
101	A	C	0.0000
102	K	C	-0.3710
103	V	C	0.0000
104	I	C	0.7718
105	T	C	0.3663
106	V	C	0.4509
107	E	C	-1.4295
108	S	C	-1.3666
109	Q	C	-1.3958
110	K	C	-0.8949
111	K	C	-0.3871
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	-1.7385
118	Q	C	-2.3951
119	H	C	-2.2364
120	K	C	-2.2099	mutated: IC120K
121	N	C	-1.1581
122	V	C	0.8057
123	N	C	-0.4996
124	E	C	0.0000
125	E	C	-1.8078
126	I	C	0.0000
127	T	C	-0.5451
128	Y	C	0.0000
129	D	C	-0.4911
130	Y	C	-0.3574
131	K	C	-0.5656
132	F	C	-0.3784
133	P	C	-0.4380
134	I	C	-0.9454
135	E	C	-2.5464
136	D	C	-2.6117
137	V	C	-1.6517
138	K	C	-1.6401
139	I	C	0.2818
140	P	C	0.5805
141	C	C	1.4768
142	L	C	1.8070
143	C	C	0.9956
144	G	C	-1.0139
145	S	C	-1.8501
146	E	C	-2.9494
147	N	C	-2.5263
148	C	C	-1.8537
149	R	C	-2.0636
150	G	C	0.0000
151	T	C	0.4839
152	L	C	0.6282
153	N	C	-0.1857

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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, -0.8747 in this case) is selected and presented in A3D results.