Aggrescan3D: 5 mutations [mutate: AX848R, TX847M, GX871W, FX843Y, TX865W]

Project name: 5 mutations [mutate: AX848R, TX847M, GX871W, FX843Y, TX865W]

Status: done

submitted: 2019-01-30 11:10:27, status changed: 2019-01-30 14:07:27

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Chain sequence(s)	X: EVTIKVNLIFADGKIQTAEFKGTFEEATAEAYRYADLLAKVNGEYTADLEDGGNHMNIKFA
Distance of aggregation	10 Å
Dynamic mode	Yes
Mutated residues	AX848R, TX847M, GX871W, FX843Y, TX865W
Energy difference between WT (input) and mutated protein (by FoldX)	-1.57579 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: -2.5288
Maximal score value: 1.091
Average score: -0.7253
Total score value: -43.5157

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
820	E	X	-1.6369
821	V	X	-0.6409
822	T	X	-1.1263
823	I	X	0.0000
824	K	X	-1.8705
825	V	X	0.0000
826	N	X	-0.8701
827	L	X	0.0000
828	I	X	0.3050
829	F	X	-0.0402
830	A	X	-0.7347
831	D	X	-1.9453
832	G	X	-1.3476
833	K	X	-1.2497
834	I	X	0.6032
835	Q	X	-0.2099
836	T	X	-0.6285
837	A	X	0.0000
838	E	X	-2.5288
839	F	X	-1.8606
840	K	X	-2.2363
841	G	X	-1.8160
842	T	X	-1.0833
843	Y	X	-0.6438	mutated: FX843Y
844	E	X	-1.9559
845	E	X	-2.0444
846	A	X	0.0000
847	M	X	-1.1004	mutated: TX847M
848	R	X	-1.9511	mutated: AX848R
849	E	X	-1.6665
850	A	X	0.0000
851	Y	X	-0.3248
852	R	X	-1.4945
853	Y	X	-0.5382
854	A	X	-0.0608
855	D	X	-0.7981
856	L	X	0.0404
857	L	X	0.0000
858	A	X	-1.0295
859	K	X	-1.2043
860	V	X	0.2074
861	N	X	-1.3842
862	G	X	-0.6888
863	E	X	-1.1103
864	Y	X	0.6989
865	W	X	1.0910	mutated: TX865W
866	A	X	0.4171
867	D	X	-0.1382
868	L	X	0.5413
869	E	X	-1.4114
870	D	X	-1.8560
871	W	X	-0.2463	mutated: GX871W
872	G	X	-0.9864
873	N	X	-0.9965
874	H	X	-1.3179
875	M	X	0.0000
876	N	X	-0.4600
877	I	X	0.0000
878	K	X	-0.2408
879	F	X	0.0547

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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, -0.7253 in this case) is selected and presented in A3D results.