Aggrescan3D: survivor [mutate: IC52D, IC23D, IC120K, RC89K]

Project name: survivor [mutate: IC52D, IC23D, IC120K, RC89K]

Status: done

submitted: 2019-10-12 13:17:35, status changed: 2019-10-12 15:45:25

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Chain sequence(s)	C: LKFNQLKFRKKKLKFCKSHIHDWGLFAMEPIAADEMVIEYVGQNIRQVIADMREKRYEDEGIGSSYMFRVDHDTIIDATKCGNFARFINHSCNPNCYAKVITVESQKKIVIYSKQHINVNEEITYDYKFPIEDVKIPCLCGSENCRGTLN
Distance of aggregation	10 Å
Dynamic mode	Yes
Mutated residues	IC52D, IC23D, IC120K, RC89K
Energy difference between WT (input) and mutated protein (by FoldX)	-3.10678 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: -4.3058
Maximal score value: 0.9363
Average score: -1.02
Total score value: -153.0052

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	0.5140
5	K	C	-0.9067
6	F	C	0.4976
7	N	C	-0.9634
8	Q	C	-1.3231
9	L	C	-0.5907
10	K	C	-1.2222
11	F	C	-0.1194
12	R	C	-1.4588
13	K	C	0.0000
14	K	C	-1.2075
15	K	C	-1.7972
16	L	C	-0.9861
17	K	C	-1.3546
18	F	C	-0.8697
19	C	C	-1.3991
20	K	C	-2.7879
21	S	C	-2.5096
22	H	C	-3.1518
23	D	C	-3.3261	mutated: IC23D
24	H	C	-2.9450
25	D	C	-3.4331
26	W	C	-2.2300
27	G	C	-1.4731
28	L	C	0.0000
29	F	C	-1.0994
30	A	C	0.0000
31	M	C	-0.6749
32	E	C	-0.6504
33	P	C	-0.0964
34	I	C	0.0000
35	A	C	-1.2850
36	A	C	-1.8021
37	D	C	-2.4623
38	E	C	0.0000
39	M	C	-0.3081
40	V	C	0.0000
41	I	C	0.0000
42	E	C	-0.1258
43	Y	C	0.0000
44	V	C	-0.0432
45	G	C	-0.6783
46	Q	C	-1.1191
47	N	C	-1.4156
48	I	C	0.0000
49	R	C	-2.6603
50	Q	C	-1.2943
51	V	C	0.4143
52	D	C	-1.2870	mutated: IC52D
53	A	C	0.0000
54	D	C	-1.2448
55	M	C	-0.9412
56	R	C	-2.0885
57	E	C	-2.9049
58	K	C	-3.9183
59	R	C	-4.1658
60	Y	C	-3.0870
61	E	C	-4.2996
62	D	C	-4.3058
63	E	C	-3.6867
64	G	C	-2.2204
65	I	C	0.4483
66	G	C	-0.9656
67	S	C	-0.5342
68	S	C	-0.2248
69	Y	C	0.0054
70	M	C	0.4700
71	F	C	0.0000
72	R	C	-1.4275
73	V	C	0.0000
74	D	C	-1.2126
75	H	C	-1.5647
76	D	C	-2.0565
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	-0.9096
83	K	C	-2.2948
84	C	C	-1.6344
85	G	C	-1.3865
86	N	C	-1.8397
87	F	C	0.0000
88	A	C	-1.3837
89	K	C	-2.3441	mutated: RC89K
90	F	C	0.0000
91	I	C	0.0000
92	N	C	0.0000
93	H	C	-0.3670
94	S	C	-0.7010
95	C	C	-0.5949
96	N	C	-1.0658
97	P	C	-1.1129
98	N	C	-2.1173
99	C	C	0.0000
100	Y	C	-0.6439
101	A	C	0.0000
102	K	C	-0.7774
103	V	C	0.0000
104	I	C	0.5499
105	T	C	0.3909
106	V	C	0.7814
107	E	C	-1.3513
108	S	C	-1.0769
109	Q	C	-0.6757
110	K	C	0.0000
111	K	C	-0.0907
112	I	C	0.0000
113	V	C	0.0000
114	I	C	0.0000
115	Y	C	-0.2746
116	S	C	0.0000
117	K	C	-2.4189
118	Q	C	-2.8037
119	H	C	-2.1768
120	K	C	-2.0967	mutated: IC120K
121	N	C	-0.8504
122	V	C	0.6339
123	N	C	-0.5959
124	E	C	0.0000
125	E	C	-1.7997
126	I	C	0.0000
127	T	C	-0.8755
128	Y	C	0.0000
129	D	C	-1.0933
130	Y	C	0.0000
131	K	C	-1.8663
132	F	C	-1.2509
133	P	C	-0.9618
134	I	C	-0.5335
135	E	C	-2.2734
136	D	C	-2.2055
137	V	C	-0.7424
138	K	C	-1.6832
139	I	C	-0.6507
140	P	C	-0.2318
141	C	C	0.2311
142	L	C	0.9363
143	C	C	0.1100
144	G	C	-1.3933
145	S	C	-1.9278
146	E	C	-2.7853
147	N	C	-2.4166
148	C	C	-1.5839
149	R	C	-2.1016
150	G	C	-0.7852
151	T	C	-0.5749
152	L	C	0.0000
153	N	C	-1.7609

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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, -1.02 in this case) is selected and presented in A3D results.