Aggrescan3D: 76-M [mutate: FA70G]

Project name: 76-M [mutate: FA70G]

Status: done

submitted: 2020-06-16 17:10:07, status changed: 2020-06-20 15:16:14

Settings

Chain sequence(s)	A: MIQRTPKIQVYSRHPAENGKSNFLNCYVSGFHPSDIEVDLLKNGERIEKVEHSDLSFSKDWSFYLLYYTEFTPTEKNEYACRVNHVTLSQPKIVKWDRDM
Distance of aggregation	10 Å
Dynamic mode	Yes
Mutated residues	FA70G
Energy difference between WT (input) and mutated protein (by FoldX)	3.9686 kcal/mol CAUTION: Your mutation/s can destabilize the protein structure 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.

Drag cursor over the plot to display residue labels.

Show buried residues

Minimal score value: -3.2496
Maximal score value: 1.8665
Average score: -0.7185
Total score value: -71.8482

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
0	M	A	1.6842
1	I	A	1.8539
2	Q	A	-0.2970
3	R	A	-0.8649
4	T	A	-0.6720
5	P	A	-1.0904
6	K	A	-1.5717
7	I	A	-0.6471
8	Q	A	-0.9537
9	V	A	0.0000
10	Y	A	-0.7704
11	S	A	0.0000
12	R	A	-0.8332
13	H	A	-1.0173
14	P	A	-1.2279
15	A	A	-1.9541
16	E	A	-2.9351
17	N	A	-2.7516
18	G	A	-2.0970
19	K	A	-2.3074
20	S	A	-1.4942
21	N	A	0.0000
22	F	A	0.0565
23	L	A	0.0000
24	N	A	0.0000
25	C	A	0.0000
26	Y	A	0.3353
27	V	A	0.0000
28	S	A	-0.0427
29	G	A	0.0000
30	F	A	0.6868
31	H	A	0.1723
32	P	A	-0.3653
33	S	A	-0.3872
34	D	A	-1.2959
35	I	A	-0.8041
36	E	A	-1.5442
37	V	A	0.0000
38	D	A	-1.4160
39	L	A	0.0000
40	L	A	0.0000
41	K	A	0.0000
42	N	A	-2.8581
43	G	A	-2.2921
44	E	A	-3.1009
45	R	A	-2.9342
46	I	A	-2.1848
47	E	A	-3.0684
48	K	A	-2.5876
49	V	A	-1.9116
50	E	A	-2.3534
51	H	A	-1.6333
52	S	A	-1.0315
53	D	A	-0.2124
54	L	A	1.6831
55	S	A	1.5845
56	F	A	1.8665
57	S	A	-0.1782
58	K	A	-1.8397
59	D	A	-1.7435
60	W	A	0.2436
61	S	A	0.7036
62	F	A	1.6114
63	Y	A	1.4792
64	L	A	0.9406
65	L	A	0.3854
66	Y	A	0.0000
67	Y	A	-0.5121
68	T	A	0.0000
69	E	A	-1.6805
70	G	A	0.0000	mutated: FA70G
71	T	A	-0.9771
72	P	A	-1.5110
73	T	A	-1.6408
74	E	A	-2.7601
75	K	A	-3.0468
76	N	A	-2.3694
77	E	A	-2.4211
78	Y	A	0.0000
79	A	A	-1.4054
80	C	A	0.0000
81	R	A	-0.6797
82	V	A	0.0000
83	N	A	-0.6756
84	H	A	0.0000
85	V	A	1.3316
86	T	A	0.9961
87	L	A	1.6041
88	S	A	0.6979
89	Q	A	0.0886
90	P	A	-0.2570
91	K	A	-0.1938
92	I	A	1.0046
93	V	A	0.1523
94	K	A	-1.8965
95	W	A	-2.1374
96	D	A	-3.2496
97	R	A	-3.2225
98	D	A	-2.5715
99	M	A	-0.5323

Download PDB file

View in JSmol

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, -0.7185 in this case) is selected and presented in A3D results.