Aggrescan3D: Trp865-Tyr843-Arg848 [mutate: AX848R, FX843Y, TX865W]

Project name: Trp865-Tyr843-Arg848 [mutate: AX848R, FX843Y, TX865W]

Status: done

submitted: 2019-01-30 09:53:13, status changed: 2019-01-30 12:55:06

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Chain sequence(s)	X: EVTIKVNLIFADGKIQTAEFKGTFEEATAEAYRYADLLAKVNGEYTADLEDGGNHMNIKFA
Distance of aggregation	10 Å
Dynamic mode	Yes
Mutated residues	AX848R, FX843Y, TX865W
Energy difference between WT (input) and mutated protein (by FoldX)	-0.744296 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: -3.1826
Maximal score value: 1.3011
Average score: -0.8444
Total score value: -50.6618

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	-1.4383
821	V	X	-0.2166
822	T	X	-1.0049
823	I	X	0.0000
824	K	X	-1.8745
825	V	X	0.0000
826	N	X	-0.4031
827	L	X	0.0000
828	I	X	1.3011
829	F	X	0.2009
830	A	X	-0.8457
831	D	X	-1.8741
832	G	X	-1.0815
833	K	X	-0.9244
834	I	X	1.0945
835	Q	X	0.3466
836	T	X	-0.1542
837	A	X	-0.9364
838	E	X	-1.8564
839	F	X	-1.3400
840	K	X	-2.1477
841	G	X	-1.6198
842	T	X	-1.2562
843	Y	X	-0.6000	mutated: FX843Y
844	E	X	-2.3605
845	E	X	-2.6589
846	A	X	0.0000
847	T	X	-1.1496
848	R	X	-2.0097	mutated: AX848R
849	E	X	-1.6286
850	A	X	0.0000
851	Y	X	-0.3178
852	R	X	-1.4425
853	Y	X	-0.4823
854	A	X	0.0000
855	D	X	-1.6189
856	L	X	0.0724
857	L	X	0.0000
858	A	X	-1.4762
859	K	X	-1.3906
860	V	X	0.1985
861	N	X	-1.1933
862	G	X	-0.7484
863	E	X	-1.5086
864	Y	X	0.1265
865	W	X	1.0528	mutated: TX865W
866	A	X	0.2415
867	D	X	-1.1566
868	L	X	-0.9147
869	E	X	-2.9499
870	D	X	-3.1826
871	G	X	-2.1046
872	G	X	-1.8782
873	N	X	-2.0723
874	H	X	-2.1769
875	M	X	0.0000
876	N	X	-0.6073
877	I	X	0.0000
878	K	X	0.2675
879	F	X	1.0387

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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, -0.8444 in this case) is selected and presented in A3D results.