Aggrescan3D: Trp865-Tyr843 [mutate: TX865W, FX843Y]

Project name: Trp865-Tyr843 [mutate: TX865W, FX843Y]

Status: done

submitted: 2019-01-30 09:34:08, status changed: 2019-01-30 11:50:30

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Chain sequence(s)	X: EVTIKVNLIFADGKIQTAEFKGTFEEATAEAYRYADLLAKVNGEYTADLEDGGNHMNIKFA
Distance of aggregation	10 Å
Dynamic mode	Yes
Mutated residues	TX865W, FX843Y
Energy difference between WT (input) and mutated protein (by FoldX)	-0.766036 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: -2.7882
Maximal score value: 1.034
Average score: -0.6902
Total score value: -41.4115

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	-1.7283
821	V	X	-0.5691
822	T	X	-1.0947
823	I	X	0.0000
824	K	X	-1.5524
825	V	X	0.0000
826	N	X	-0.5106
827	L	X	0.1697
828	I	X	0.5076
829	F	X	0.2209
830	A	X	-0.8466
831	D	X	-2.1272
832	G	X	-1.4948
833	K	X	-1.2215
834	I	X	0.7932
835	Q	X	-0.5234
836	T	X	-0.7018
837	A	X	-1.1781
838	E	X	-1.8637
839	F	X	-1.3208
840	K	X	-2.2100
841	G	X	0.0000
842	T	X	-1.2300
843	Y	X	-0.5707	mutated: FX843Y
844	E	X	-2.1444
845	E	X	-2.3709
846	A	X	0.0000
847	T	X	-1.0020
848	A	X	-0.9772
849	E	X	-1.3284
850	A	X	0.0000
851	Y	X	0.2220
852	R	X	-1.0172
853	Y	X	-0.1730
854	A	X	-0.0415
855	D	X	-0.5228
856	L	X	0.7742
857	L	X	0.0000
858	A	X	-0.2320
859	K	X	-0.8265
860	V	X	1.0031
861	N	X	0.0207
862	G	X	-0.8486
863	E	X	-0.6649
864	Y	X	0.5413
865	W	X	1.0340	mutated: TX865W
866	A	X	0.2730
867	D	X	-0.7630
868	L	X	-0.4360
869	E	X	-2.5986
870	D	X	-2.7882
871	G	X	-2.0353
872	G	X	-1.6597
873	N	X	-1.5153
874	H	X	-1.9174
875	M	X	-1.0315
876	N	X	-0.5229
877	I	X	0.0000
878	K	X	0.3772
879	F	X	0.8126

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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, -0.6902 in this case) is selected and presented in A3D results.