Aggrescan3D: Arg848-Met847-Trp865 [mutate: AX848R, TX847M, TX865W]

Project name: Arg848-Met847-Trp865 [mutate: AX848R, TX847M, TX865W]

Status: done

submitted: 2019-01-30 09:39:33, status changed: 2019-01-30 12:02:07

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Chain sequence(s)	X: EVTIKVNLIFADGKIQTAEFKGTFEEATAEAYRYADLLAKVNGEYTADLEDGGNHMNIKFA
Distance of aggregation	10 Å
Dynamic mode	Yes
Mutated residues	AX848R, TX847M, TX865W
Energy difference between WT (input) and mutated protein (by FoldX)	-2.47981 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: -3.1897
Maximal score value: 1.2948
Average score: -0.75
Total score value: -44.9999

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	-1.7778
821	V	X	-0.6691
822	T	X	-1.2469
823	I	X	0.0000
824	K	X	-1.7494
825	V	X	0.0000
826	N	X	-0.6669
827	L	X	0.5089
828	I	X	1.2414
829	F	X	1.2948
830	A	X	-0.1470
831	D	X	-1.8592
832	G	X	-1.1887
833	K	X	-0.8286
834	I	X	1.1979
835	Q	X	-0.4488
836	T	X	-0.8155
837	A	X	-1.0834
838	E	X	-2.4769
839	F	X	-1.5394
840	K	X	-2.2568
841	G	X	-1.2314
842	T	X	-0.3883
843	F	X	0.2840
844	E	X	-1.3835
845	E	X	-1.1907
846	A	X	0.0000
847	M	X	-0.3692	mutated: TX847M
848	R	X	-1.5481	mutated: AX848R
849	E	X	-1.2961
850	A	X	0.0000
851	Y	X	0.1608
852	R	X	-0.9904
853	Y	X	-0.0014
854	A	X	0.2456
855	D	X	-0.4552
856	L	X	0.7388
857	L	X	0.0000
858	A	X	-0.8743
859	K	X	-1.1916
860	V	X	0.4215
861	N	X	-1.4669
862	G	X	-1.6916
863	E	X	-1.8946
864	Y	X	-0.2563
865	W	X	0.6506	mutated: TX865W
866	A	X	-0.0971
867	D	X	-0.7693
868	L	X	-1.1993
869	E	X	-2.9949
870	D	X	-3.1897
871	G	X	-2.1066
872	G	X	-1.9373
873	N	X	-2.0786
874	H	X	-2.2081
875	M	X	0.0000
876	N	X	-0.7816
877	I	X	0.0000
878	K	X	0.0136
879	F	X	0.5887

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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, -0.75 in this case) is selected and presented in A3D results.