Aggrescan3D: Trp865-Met847-Trp871 [mutate: TX847M, GX871W, TX865W]

Project name: Trp865-Met847-Trp871 [mutate: TX847M, GX871W, TX865W]

Status: done

submitted: 2019-01-30 09:48:24, status changed: 2019-01-30 12:08:18

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Chain sequence(s)	X: EVTIKVNLIFADGKIQTAEFKGTFEEATAEAYRYADLLAKVNGEYTADLEDGGNHMNIKFA
Distance of aggregation	10 Å
Dynamic mode	Yes
Mutated residues	TX847M, GX871W, TX865W
Energy difference between WT (input) and mutated protein (by FoldX)	-0.908614 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: -2.7554
Maximal score value: 1.5793
Average score: -0.6886
Total score value: -41.3137

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	-1.7668
821	V	X	-0.6060
822	T	X	-1.2391
823	I	X	0.0000
824	K	X	-2.4265
825	V	X	0.0000
826	N	X	-0.6433
827	L	X	0.0000
828	I	X	0.9470
829	F	X	0.3927
830	A	X	-0.2869
831	D	X	-1.7812
832	G	X	-1.3582
833	K	X	-1.3914
834	I	X	0.5056
835	Q	X	-0.6225
836	T	X	-0.8292
837	A	X	-1.4571
838	E	X	-2.7554
839	F	X	-1.7821
840	K	X	-2.4854
841	G	X	0.0000
842	T	X	-1.1373
843	F	X	-0.9771
844	E	X	-2.2035
845	E	X	-2.6126
846	A	X	0.0000
847	M	X	-0.7979	mutated: TX847M
848	A	X	-0.8990
849	E	X	-1.5997
850	A	X	0.0000
851	Y	X	0.3560
852	R	X	-1.2541
853	Y	X	0.0000
854	A	X	0.0856
855	D	X	-0.8132
856	L	X	0.3864
857	L	X	0.0000
858	A	X	-0.9389
859	K	X	-1.0195
860	V	X	0.4871
861	N	X	-1.3092
862	G	X	-0.5791
863	E	X	-1.1075
864	Y	X	0.4893
865	W	X	0.8431	mutated: TX865W
866	A	X	0.2955
867	D	X	-0.9904
868	L	X	-0.4413
869	E	X	-2.2022
870	D	X	-2.0433
871	W	X	-0.0464	mutated: GX871W
872	G	X	-0.7728
873	N	X	-1.1578
874	H	X	-1.7439
875	M	X	0.0000
876	N	X	-0.4801
877	I	X	0.0000
878	K	X	0.8766
879	F	X	1.5793

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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, -0.6886 in this case) is selected and presented in A3D results.