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

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

Status: done

submitted: 2019-01-30 09:37:38, status changed: 2019-01-30 11:55:39

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Chain sequence(s)	X: EVTIKVNLIFADGKIQTAEFKGTFEEATAEAYRYADLLAKVNGEYTADLEDGGNHMNIKFA
Distance of aggregation	10 Å
Dynamic mode	Yes
Mutated residues	FX843Y, GX871W
Energy difference between WT (input) and mutated protein (by FoldX)	1.00804 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: -2.8586
Maximal score value: 1.1068
Average score: -0.6724
Total score value: -40.3418

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	-1.5625
821	V	X	-0.5731
822	T	X	-0.9796
823	I	X	0.0000
824	K	X	-1.3775
825	V	X	0.0000
826	N	X	-0.2793
827	L	X	0.0000
828	I	X	0.7785
829	F	X	0.2968
830	A	X	-0.4802
831	D	X	-1.7630
832	G	X	-1.3078
833	K	X	-0.7051
834	I	X	1.1068
835	Q	X	0.4230
836	T	X	-0.2648
837	A	X	0.0000
838	E	X	-2.4697
839	F	X	0.0000
840	K	X	-2.8586
841	G	X	-1.9581
842	T	X	-1.1685
843	Y	X	-0.8865	mutated: FX843Y
844	E	X	-2.4740
845	E	X	-2.5428
846	A	X	0.0000
847	T	X	-1.2527
848	A	X	-1.1779
849	E	X	-1.7308
850	A	X	0.0000
851	Y	X	0.2369
852	R	X	-0.9796
853	Y	X	-0.0051
854	A	X	-0.0810
855	D	X	-0.4716
856	L	X	0.7906
857	L	X	0.4925
858	A	X	-0.9068
859	K	X	-0.8116
860	V	X	0.7330
861	N	X	-1.0422
862	G	X	-0.9762
863	E	X	-1.7336
864	Y	X	-0.3997
865	T	X	-0.4851
866	A	X	-0.4628
867	D	X	-1.0789
868	L	X	-0.1779
869	E	X	-2.0286
870	D	X	-2.0224
871	W	X	-0.3216	mutated: GX871W
872	G	X	-0.4634
873	N	X	-0.8179
874	H	X	-1.1356
875	M	X	-0.6312
876	N	X	-0.5285
877	I	X	0.0000
878	K	X	-0.4519
879	F	X	0.6258

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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, -0.6724 in this case) is selected and presented in A3D results.