Aggrescan3D: Arg848-Tyr843-Met847 [mutate: FX843Y, AX848R, TX847M]

Project name: Arg848-Tyr843-Met847 [mutate: FX843Y, AX848R, TX847M]

Status: done

submitted: 2019-01-30 09:44:23, status changed: 2019-01-30 12:08:09

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Chain sequence(s)	X: EVTIKVNLIFADGKIQTAEFKGTFEEATAEAYRYADLLAKVNGEYTADLEDGGNHMNIKFA
Distance of aggregation	10 Å
Dynamic mode	Yes
Mutated residues	FX843Y, AX848R, TX847M
Energy difference between WT (input) and mutated protein (by FoldX)	-2.98048 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: -3.1965
Maximal score value: 1.0719
Average score: -0.8566
Total score value: -51.3963

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	-2.0353
821	V	X	0.0000
822	T	X	-1.8567
823	I	X	0.0000
824	K	X	-2.1297
825	V	X	0.0000
826	N	X	-0.5479
827	L	X	0.5006
828	I	X	0.7002
829	F	X	0.1079
830	A	X	-0.6036
831	D	X	-2.0386
832	G	X	-1.3036
833	K	X	-0.9317
834	I	X	1.0719
835	Q	X	0.0037
836	T	X	-0.5254
837	A	X	0.0000
838	E	X	-2.5006
839	F	X	-1.6324
840	K	X	-2.4396
841	G	X	-1.8405
842	T	X	-1.1660
843	Y	X	-0.6749	mutated: FX843Y
844	E	X	-1.9210
845	E	X	-1.6807
846	A	X	0.0000
847	M	X	-0.3311	mutated: TX847M
848	R	X	-1.2346	mutated: AX848R
849	E	X	-1.0542
850	A	X	-0.3956
851	Y	X	0.2752
852	R	X	-1.1573
853	Y	X	0.0000
854	A	X	-0.1947
855	D	X	-0.8669
856	L	X	0.0095
857	L	X	0.0000
858	A	X	-1.0935
859	K	X	-1.3079
860	V	X	0.2597
861	N	X	-1.2667
862	G	X	-0.6851
863	E	X	-1.0352
864	Y	X	0.3759
865	T	X	0.0311
866	A	X	0.1315
867	D	X	-0.7469
868	L	X	-0.6246
869	E	X	-2.8136
870	D	X	-3.1965
871	G	X	-2.3353
872	G	X	-2.2986
873	N	X	-2.7413
874	H	X	-2.3841
875	M	X	-1.3627
876	N	X	-0.4344
877	I	X	0.0000
878	K	X	-0.1427
879	F	X	0.6682

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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, -0.8566 in this case) is selected and presented in A3D results.