Aggrescan3D: Tyr843-Trp871-Arg848 [mutate: FX843Y, GX871W, AX848R]

Project name: Tyr843-Trp871-Arg848 [mutate: FX843Y, GX871W, AX848R]

Status: done

submitted: 2019-01-30 11:07:45, status changed: 2019-01-30 14:07:06

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Chain sequence(s)	X: EVTIKVNLIFADGKIQTAEFKGTFEEATAEAYRYADLLAKVNGEYTADLEDGGNHMNIKFA
Distance of aggregation	10 Å
Dynamic mode	Yes
Mutated residues	FX843Y, GX871W, AX848R
Energy difference between WT (input) and mutated protein (by FoldX)	1.02978 kcal/mol CAUTION: Your mutation/s can destabilize the protein structure 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: -2.7155
Maximal score value: 1.352
Average score: -0.753
Total score value: -45.1808

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	-1.6947
821	V	X	-0.7991
822	T	X	-1.2754
823	I	X	0.0000
824	K	X	-1.6324
825	V	X	0.0000
826	N	X	-0.4072
827	L	X	0.0000
828	I	X	0.9852
829	F	X	0.0000
830	A	X	-0.8213
831	D	X	-1.8527
832	G	X	-1.1151
833	K	X	-0.4640
834	I	X	1.3520
835	Q	X	0.2719
836	T	X	-0.4403
837	A	X	0.0000
838	E	X	-2.4813
839	F	X	-1.9521
840	K	X	-2.6850
841	G	X	-1.9080
842	T	X	-1.2351
843	Y	X	-1.0884	mutated: FX843Y
844	E	X	-2.6264
845	E	X	-2.7155
846	A	X	0.0000
847	T	X	-1.8204
848	R	X	-2.3169	mutated: AX848R
849	E	X	-2.4344
850	A	X	0.0000
851	Y	X	-0.3032
852	R	X	-1.5807
853	Y	X	-0.5338
854	A	X	-0.0580
855	D	X	-0.4876
856	L	X	0.7687
857	L	X	0.0000
858	A	X	-0.5046
859	K	X	-0.9041
860	V	X	0.8116
861	N	X	-0.3998
862	G	X	-1.1523
863	E	X	-1.6060
864	Y	X	0.0870
865	T	X	-0.1504
866	A	X	-0.1884
867	D	X	-0.9749
868	L	X	0.3322
869	E	X	-0.9831
870	D	X	-1.5615
871	W	X	-0.1345	mutated: GX871W
872	G	X	-0.5842
873	N	X	-0.5933
874	H	X	-0.8367
875	M	X	-0.5575
876	N	X	-0.6200
877	I	X	0.0000
878	K	X	-0.9840
879	F	X	-0.3251

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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, -0.753 in this case) is selected and presented in A3D results.