Aggrescan3D: survivor [mutate: IC23D]

Project name: survivor [mutate: IC23D]

Status: done

submitted: 2019-09-02 13:58:44, status changed: 2019-09-02 16:25:16

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Chain sequence(s)	C: LKFNQLKFRKKKLKFCKSHIHDWGLFAMEPIAADEMVIEYVGQNIRQVIADMREKRYEDEGIGSSYMFRVDHDTIIDATKCGNFARFINHSCNPNCYAKVITVESQKKIVIYSKQHINVNEEITYDYKFPIEDVKIPCLCGSENCRGTLN
Distance of aggregation	10 Å
Dynamic mode	Yes
Mutated residues	IC23D
Energy difference between WT (input) and mutated protein (by FoldX)	-0.448547 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: -4.6124
Maximal score value: 2.2649
Average score: -0.8751
Total score value: -131.2635

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	1.2262
5	K	C	-0.5927
6	F	C	0.4025
7	N	C	-1.5171
8	Q	C	-2.2618
9	L	C	0.0000
10	K	C	-1.7739
11	F	C	0.0000
12	R	C	-2.6468
13	K	C	-3.5647
14	K	C	-3.2547
15	K	C	-2.2364
16	L	C	-1.3517
17	K	C	-1.0077
18	F	C	0.4587
19	C	C	0.0196
20	K	C	-1.8804
21	S	C	-2.1324
22	H	C	-2.7089
23	D	C	-2.8518	mutated: IC23D
24	H	C	0.0000
25	D	C	-2.3348
26	W	C	0.0000
27	G	C	-0.7331
28	L	C	0.0000
29	F	C	-0.3285
30	A	C	0.0000
31	M	C	-0.8276
32	E	C	-0.3259
33	P	C	0.4125
34	I	C	0.0000
35	A	C	0.0821
36	A	C	-1.0159
37	D	C	-2.6633
38	E	C	0.0000
39	M	C	0.0000
40	V	C	0.0000
41	I	C	0.0000
42	E	C	-1.0736
43	Y	C	0.0000
44	V	C	0.0000
45	G	C	-0.8815
46	Q	C	-0.9505
47	N	C	-1.1293
48	I	C	-0.6064
49	R	C	-1.5264
50	Q	C	-0.7020
51	V	C	1.8853
52	I	C	2.2649
53	A	C	0.0000
54	D	C	-0.0922
55	M	C	0.5674
56	R	C	-1.0218
57	E	C	-2.4746
58	K	C	-4.0542
59	R	C	-4.1010
60	Y	C	-2.7988
61	E	C	-4.1209
62	D	C	-4.6124
63	E	C	-3.6532
64	G	C	-2.2350
65	I	C	0.3424
66	G	C	0.1550
67	S	C	-0.1757
68	S	C	-0.1465
69	Y	C	-0.1223
70	M	C	0.1260
71	F	C	-0.0858
72	R	C	-1.6937
73	V	C	0.0000
74	D	C	-2.8604
75	H	C	-2.7735
76	D	C	-2.3868
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	-0.7959
83	K	C	-1.9395
84	C	C	-1.3758
85	G	C	-1.2856
86	N	C	-1.9753
87	F	C	-1.4347
88	A	C	0.0000
89	R	C	-0.2946
90	F	C	0.0000
91	I	C	0.0091
92	N	C	0.0000
93	H	C	-0.6258
94	S	C	0.0000
95	C	C	-0.5174
96	N	C	-0.9747
97	P	C	-0.8113
98	N	C	-1.1283
99	C	C	0.0000
100	Y	C	-0.6266
101	A	C	0.0000
102	K	C	-1.2928
103	V	C	0.0000
104	I	C	0.7412
105	T	C	0.3401
106	V	C	0.6480
107	E	C	-1.2453
108	S	C	-1.1646
109	Q	C	-0.7030
110	K	C	0.0000
111	K	C	-0.7532
112	I	C	0.0000
113	V	C	0.0000
114	I	C	0.0000
115	Y	C	-0.7954
116	S	C	0.0000
117	K	C	-2.6550
118	Q	C	-1.9006
119	H	C	-1.3502
120	I	C	0.7939
121	N	C	0.0700
122	V	C	1.2784
123	N	C	-0.1580
124	E	C	0.0000
125	E	C	-1.3183
126	I	C	0.0000
127	T	C	0.0000
128	Y	C	0.0000
129	D	C	-1.0912
130	Y	C	0.0000
131	K	C	-2.3569
132	F	C	0.0000
133	P	C	-1.4406
134	I	C	-1.2505
135	E	C	-2.5446
136	D	C	-2.4806
137	V	C	-1.3619
138	K	C	-2.6648
139	I	C	0.0000
140	P	C	-1.2302
141	C	C	-0.3481
142	L	C	0.7802
143	C	C	-0.0933
144	G	C	-1.5820
145	S	C	-2.1946
146	E	C	-2.9224
147	N	C	-2.4358
148	C	C	-1.9652
149	R	C	-2.3239
150	G	C	0.0000
151	T	C	-0.3675
152	L	C	0.0000
153	N	C	-1.8024

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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, -0.8751 in this case) is selected and presented in A3D results.