Aggrescan3D: Trp865-Met847-Tyr843 [mutate: TX847M, FX843Y, TX865W]

Project name: Trp865-Met847-Tyr843 [mutate: TX847M, FX843Y, TX865W]

Status: done

submitted: 2019-01-30 09:50:05, status changed: 2019-01-30 12:13:05

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Chain sequence(s)	X: EVTIKVNLIFADGKIQTAEFKGTFEEATAEAYRYADLLAKVNGEYTADLEDGGNHMNIKFA
Distance of aggregation	10 Å
Dynamic mode	Yes
Mutated residues	TX847M, FX843Y, TX865W
Energy difference between WT (input) and mutated protein (by FoldX)	-3.20552 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: -2.6623
Maximal score value: 1.8258
Average score: -0.6962
Total score value: -41.7733

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	-1.6401
821	V	X	-0.7270
822	T	X	-1.2015
823	I	X	0.0000
824	K	X	-1.6624
825	V	X	0.0000
826	N	X	-0.7139
827	L	X	0.0000
828	I	X	0.7678
829	F	X	0.6577
830	A	X	-0.3723
831	D	X	-2.0480
832	G	X	-1.6132
833	K	X	-1.4767
834	I	X	0.4505
835	Q	X	-0.5954
836	T	X	-0.7059
837	A	X	-1.5855
838	E	X	-2.4199
839	F	X	-1.7170
840	K	X	-2.4146
841	G	X	-1.8959
842	T	X	-1.1028
843	Y	X	-0.5270	mutated: FX843Y
844	E	X	-1.9124
845	E	X	-2.4248
846	A	X	0.0000
847	M	X	-0.8450	mutated: TX847M
848	A	X	-1.2585
849	E	X	-1.5570
850	A	X	0.0000
851	Y	X	-0.0323
852	R	X	-1.2245
853	Y	X	-0.2553
854	A	X	0.2890
855	D	X	-0.5951
856	L	X	0.4673
857	L	X	0.3213
858	A	X	-0.5949
859	K	X	-0.9317
860	V	X	0.3192
861	N	X	-1.2282
862	G	X	-0.7041
863	E	X	-0.8917
864	Y	X	0.8710
865	W	X	1.3370	mutated: TX865W
866	A	X	0.7285
867	D	X	-0.2708
868	L	X	-0.4181
869	E	X	-1.9744
870	D	X	-2.6623
871	G	X	-1.8080
872	G	X	-1.2525
873	N	X	-1.3122
874	H	X	-1.9927
875	M	X	0.0000
876	N	X	-0.1564
877	I	X	0.0000
878	K	X	0.9136
879	F	X	1.8258

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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, -0.6962 in this case) is selected and presented in A3D results.