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

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

Status: done

submitted: 2019-01-30 09:36:31, status changed: 2019-01-30 11:56:13

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Chain sequence(s)	X: EVTIKVNLIFADGKIQTAEFKGTFEEATAEAYRYADLLAKVNGEYTADLEDGGNHMNIKFA
Distance of aggregation	10 Å
Dynamic mode	Yes
Mutated residues	AX848R, FX843Y
Energy difference between WT (input) and mutated protein (by FoldX)	-0.59263 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: -2.9418
Maximal score value: 1.2175
Average score: -0.8346
Total score value: -50.0785

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	-1.7119
821	V	X	-0.7478
822	T	X	-1.2043
823	I	X	0.0000
824	K	X	-2.4167
825	V	X	0.0000
826	N	X	-1.0771
827	L	X	0.0000
828	I	X	1.1241
829	F	X	0.0000
830	A	X	-0.6775
831	D	X	-1.9821
832	G	X	-1.3027
833	K	X	-1.2483
834	I	X	0.7555
835	Q	X	0.2094
836	T	X	-0.4106
837	A	X	-1.4910
838	E	X	-2.3383
839	F	X	0.0000
840	K	X	-2.4391
841	G	X	-1.7157
842	T	X	-1.2887
843	Y	X	-0.7144	mutated: FX843Y
844	E	X	-1.9881
845	E	X	-2.1605
846	A	X	0.0000
847	T	X	-1.2528
848	R	X	-1.7026	mutated: AX848R
849	E	X	-1.4416
850	A	X	0.0000
851	Y	X	0.0973
852	R	X	-0.8989
853	Y	X	-0.1913
854	A	X	0.1729
855	D	X	-0.5960
856	L	X	0.2780
857	L	X	0.0000
858	A	X	-0.9450
859	K	X	-1.1079
860	V	X	0.2422
861	N	X	-1.4575
862	G	X	-0.8806
863	E	X	-0.9637
864	Y	X	0.6616
865	T	X	0.3290
866	A	X	-0.2129
867	D	X	-0.8889
868	L	X	-0.4867
869	E	X	-2.5953
870	D	X	-2.9418
871	G	X	-2.1877
872	G	X	-1.8864
873	N	X	-1.8546
874	H	X	-2.2056
875	M	X	-1.3034
876	N	X	-0.7511
877	I	X	0.0000
878	K	X	0.5011
879	F	X	1.2175

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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, -0.8346 in this case) is selected and presented in A3D results.