Aggrescan3D: 76-23L [mutate: LA23G]

Project name: 76-23L [mutate: LA23G]

Status: done

submitted: 2020-06-16 17:14:53, status changed: 2020-06-20 17:39:05

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Chain sequence(s)	A: MIQRTPKIQVYSRHPAENGKSNFLNCYVSGFHPSDIEVDLLKNGERIEKVEHSDLSFSKDWSFYLLYYTEFTPTEKNEYACRVNHVTLSQPKIVKWDRDM
Distance of aggregation	10 Å
Dynamic mode	Yes
Mutated residues	LA23G
Energy difference between WT (input) and mutated protein (by FoldX)	5.21838 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.

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Minimal score value: -3.377
Maximal score value: 2.1114
Average score: -0.7183
Total score value: -71.831

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	1.6425
1	I	A	1.8479
2	Q	A	-0.2965
3	R	A	-1.0002
4	T	A	-0.7916
5	P	A	-1.0666
6	K	A	-1.3778
7	I	A	0.0000
8	Q	A	-0.5235
9	V	A	0.0000
10	Y	A	-0.6506
11	S	A	0.0000
12	R	A	-0.7476
13	H	A	-1.5064
14	P	A	-1.4935
15	A	A	-1.7280
16	E	A	-2.8880
17	N	A	-3.1040
18	G	A	-2.3582
19	K	A	-2.7624
20	S	A	-1.8912
21	N	A	0.0000
22	F	A	-0.6313
23	G	A	0.0000	mutated: LA23G
24	N	A	0.0000
25	C	A	0.0000
26	Y	A	0.3992
27	V	A	0.0000
28	S	A	0.0022
29	G	A	0.0000
30	F	A	0.5942
31	H	A	0.2762
32	P	A	-0.1048
33	S	A	0.0000
34	D	A	-1.4812
35	I	A	-1.3331
36	E	A	-2.3126
37	V	A	-1.1745
38	D	A	0.0000
39	L	A	0.0000
40	L	A	-1.4560
41	K	A	0.0000
42	N	A	-2.7393
43	G	A	-2.0226
44	E	A	-2.5441
45	R	A	-2.4931
46	I	A	0.0000
47	E	A	-2.9529
48	K	A	-2.7139
49	V	A	-1.5177
50	E	A	-2.3854
51	H	A	-2.1587
52	S	A	-1.3427
53	D	A	-1.1442
54	L	A	1.4607
55	S	A	1.5675
56	F	A	2.1114
57	S	A	-0.0699
58	K	A	-1.8601
59	D	A	-1.8609
60	W	A	0.5207
61	S	A	0.9227
62	F	A	1.4043
63	Y	A	1.6410
64	L	A	0.0000
65	L	A	0.4787
66	Y	A	-0.1551
67	Y	A	-0.7273
68	T	A	0.0000
69	E	A	-1.8296
70	F	A	0.0000
71	T	A	-1.0386
72	P	A	-1.6292
73	T	A	-1.3182
74	E	A	-3.1399
75	K	A	-3.3770
76	N	A	-2.8616
77	E	A	-3.0360
78	Y	A	0.0000
79	A	A	-0.9353
80	C	A	0.0000
81	R	A	-0.4225
82	V	A	0.0000
83	N	A	-1.2907
84	H	A	0.0000
85	V	A	0.5655
86	T	A	0.7326
87	L	A	1.1930
88	S	A	0.4680
89	Q	A	0.0113
90	P	A	-0.4684
91	K	A	-0.3305
92	I	A	1.1716
93	V	A	0.1558
94	K	A	-1.1216
95	W	A	-0.5083
96	D	A	-1.7507
97	R	A	-2.0560
98	D	A	-2.0932
99	M	A	-0.4232

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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, -0.7183 in this case) is selected and presented in A3D results.