Aggrescan3D: 2a60d4f281d2f4f [mutate: RA5Q, GA8L, PA13T]

Project name: 2a60d4f281d2f4f [mutate: RA5Q, GA8L, PA13T]

Status: done

submitted: 2019-11-28 14:23:55, status changed: 2019-11-28 22:06:31

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Chain sequence(s)	A: PADGRVRGIGYDPETGTWGLWDSSTLGAILM
Distance of aggregation	10 Å
Dynamic mode	Yes
Mutated residues	RA5Q, GA8L, PA13T
Energy difference between WT (input) and mutated protein (by FoldX)	1.23486 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: -2.1153
Maximal score value: 3.2239
Average score: 0.6387
Total score value: 19.7986

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
1	P	A	-1.0383
2	A	A	-1.3698
3	D	A	-2.0098
4	G	A	-1.5236
5	Q	A	-1.4114	mutated: RA5Q
6	V	A	0.1974
7	R	A	-0.3180
8	L	A	2.1528	mutated: GA8L
9	I	A	3.2239
10	G	A	2.1910
11	Y	A	1.6502
12	D	A	-0.8767
13	T	A	-1.3493	mutated: PA13T
14	E	A	-2.1153
15	T	A	-1.2581
16	G	A	-0.9439
17	T	A	-0.3642
18	W	A	1.1038
19	G	A	1.4953
20	L	A	2.8850
21	W	A	2.4657
22	D	A	1.1842
23	S	A	0.8138
24	S	A	0.3688
25	T	A	1.1322
26	L	A	1.7699
27	G	A	1.1181
28	A	A	1.9274
29	I	A	3.1838
30	L	A	3.0172
31	M	A	2.4965

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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, 0.6387 in this case) is selected and presented in A3D results.