Aggrescan3D: survivor [mutate: IC52D, IC23D, IC120K, FC87D, RC89K]

Project name: survivor [mutate: IC52D, IC23D, IC120K, FC87D, RC89K]

Status: done

submitted: 2019-10-12 04:32:43, status changed: 2019-10-12 07:00:25

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Chain sequence(s)	C: LKFNQLKFRKKKLKFCKSHIHDWGLFAMEPIAADEMVIEYVGQNIRQVIADMREKRYEDEGIGSSYMFRVDHDTIIDATKCGNFARFINHSCNPNCYAKVITVESQKKIVIYSKQHINVNEEITYDYKFPIEDVKIPCLCGSENCRGTLN
Distance of aggregation	10 Å
Dynamic mode	Yes
Mutated residues	IC52D, IC23D, IC120K, FC87D, RC89K
Energy difference between WT (input) and mutated protein (by FoldX)	-3.81587 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: -4.3499
Maximal score value: 1.1661
Average score: -1.019
Total score value: -152.8475

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	0.6847
5	K	C	-1.0359
6	F	C	0.0374
7	N	C	-1.2945
8	Q	C	-1.0219
9	L	C	0.0000
10	K	C	-1.3951
11	F	C	0.5858
12	R	C	-0.5865
13	K	C	0.0000
14	K	C	-2.0542
15	K	C	-2.7804
16	L	C	0.0000
17	K	C	-1.6465
18	F	C	-0.0513
19	C	C	0.1579
20	K	C	-1.2197
21	S	C	-1.5842
22	H	C	-2.4021
23	D	C	-2.8759	mutated: IC23D
24	H	C	-2.5150
25	D	C	-1.9134
26	W	C	-0.8078
27	G	C	-0.3827
28	L	C	0.0000
29	F	C	-0.3225
30	A	C	0.0000
31	M	C	-1.1168
32	E	C	-0.8592
33	P	C	-0.6699
34	I	C	0.0000
35	A	C	-0.9326
36	A	C	-1.4046
37	D	C	-1.5225
38	E	C	0.0000
39	M	C	0.0874
40	V	C	0.0000
41	I	C	-1.0081
42	E	C	-2.2557
43	Y	C	0.0000
44	V	C	0.0000
45	G	C	-1.7678
46	Q	C	-1.7131
47	N	C	-2.5397
48	I	C	0.0000
49	R	C	-2.8312
50	Q	C	-1.5333
51	V	C	0.3460
52	D	C	-1.0558	mutated: IC52D
53	A	C	0.0000
54	D	C	-1.0235
55	M	C	-0.2225
56	R	C	0.0000
57	E	C	-2.1981
58	K	C	-3.5004
59	R	C	-3.6201
60	Y	C	0.0000
61	E	C	-3.9294
62	D	C	-4.3499
63	E	C	-3.7234
64	G	C	-2.1907
65	I	C	-0.2737
66	G	C	-0.6152
67	S	C	-0.4258
68	S	C	-0.0275
69	Y	C	0.0000
70	M	C	-0.1008
71	F	C	0.0000
72	R	C	-1.5079
73	V	C	0.0000
74	D	C	-2.4843
75	H	C	-2.7253
76	D	C	-2.5135
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	-1.3315
83	K	C	-2.1064
84	C	C	-1.7981
85	G	C	-2.1091
86	N	C	-2.4712
87	D	C	-2.5145	mutated: FC87D
88	A	C	-2.2987
89	K	C	-1.6864	mutated: RC89K
90	F	C	0.0000
91	I	C	0.0000
92	N	C	0.0000
93	H	C	0.0000
94	S	C	-1.1231
95	C	C	-1.2875
96	N	C	-1.7326
97	P	C	-1.0438
98	N	C	-1.1613
99	C	C	0.0000
100	Y	C	0.0699
101	A	C	0.0000
102	K	C	-0.9668
103	V	C	0.0000
104	I	C	0.0718
105	T	C	-0.2550
106	V	C	0.0143
107	E	C	-1.6461
108	S	C	-1.5365
109	Q	C	-1.3507
110	K	C	0.0000
111	K	C	-1.4763
112	I	C	0.0000
113	V	C	0.0000
114	I	C	0.0000
115	Y	C	-0.0771
116	S	C	0.0000
117	K	C	-2.5004
118	Q	C	-2.2676
119	H	C	-2.3936
120	K	C	-2.2339	mutated: IC120K
121	N	C	-1.3400
122	V	C	0.4467
123	N	C	-0.5464
124	E	C	0.0000
125	E	C	-1.2506
126	I	C	0.0000
127	T	C	-0.6454
128	Y	C	0.0000
129	D	C	-1.1379
130	Y	C	0.0000
131	K	C	-1.7130
132	F	C	-0.8066
133	P	C	-0.4299
134	I	C	0.4559
135	E	C	-1.5890
136	D	C	-2.2008
137	V	C	-1.9355
138	K	C	-2.6745
139	I	C	-1.2868
140	P	C	-0.4278
141	C	C	0.4630
142	L	C	1.1661
143	C	C	-0.2999
144	G	C	-1.0414
145	S	C	-2.0620
146	E	C	-3.1297
147	N	C	-2.6017
148	C	C	-2.3929
149	R	C	-2.6209
150	G	C	-0.9815
151	T	C	-0.0792
152	L	C	-0.6884
153	N	C	-1.6525

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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, -1.019 in this case) is selected and presented in A3D results.