Aggrescan3D: Arg848-Trp871-Met847 [mutate: TX847M, AX848R, GX871W]

Project name: Arg848-Trp871-Met847 [mutate: TX847M, AX848R, GX871W]

Status: done

submitted: 2019-01-30 09:41:08, status changed: 2019-01-30 12:01:38

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Chain sequence(s)	X: EVTIKVNLIFADGKIQTAEFKGTFEEATAEAYRYADLLAKVNGEYTADLEDGGNHMNIKFA
Distance of aggregation	10 Å
Dynamic mode	Yes
Mutated residues	TX847M, AX848R, GX871W
Energy difference between WT (input) and mutated protein (by FoldX)	-0.708461 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: -2.4953
Maximal score value: 1.7056
Average score: -0.7056
Total score value: -42.336

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	-1.7667
821	V	X	-1.0263
822	T	X	-1.3634
823	I	X	0.0000
824	K	X	-1.9371
825	V	X	0.0000
826	N	X	-0.6198
827	L	X	0.0000
828	I	X	1.7056
829	F	X	0.4665
830	A	X	-0.4947
831	D	X	-1.7833
832	G	X	-1.4338
833	K	X	-1.0830
834	I	X	1.1151
835	Q	X	0.1043
836	T	X	-0.3873
837	A	X	-1.2634
838	E	X	-2.4953
839	F	X	-1.7328
840	K	X	-2.4261
841	G	X	-1.5484
842	T	X	-0.9334
843	F	X	-0.1957
844	E	X	-1.8097
845	E	X	-1.8092
846	A	X	0.0000
847	M	X	-1.0868	mutated: TX847M
848	R	X	-1.6149	mutated: AX848R
849	E	X	-1.5485
850	A	X	0.0000
851	Y	X	-0.1383
852	R	X	-1.3735
853	Y	X	-0.5467
854	A	X	-0.5085
855	D	X	-1.6416
856	L	X	-0.0347
857	L	X	0.0000
858	A	X	-1.2721
859	K	X	-1.3707
860	V	X	0.0577
861	N	X	-1.3322
862	G	X	-0.7382
863	E	X	-1.0356
864	Y	X	0.4282
865	T	X	0.0790
866	A	X	-0.0783
867	D	X	-0.4959
868	L	X	0.0557
869	E	X	-1.5074
870	D	X	-1.7221
871	W	X	-0.3200	mutated: GX871W
872	G	X	-0.7519
873	N	X	-0.9104
874	H	X	-1.3542
875	M	X	0.0000
876	N	X	-0.3137
877	I	X	0.0000
878	K	X	0.1773
879	F	X	1.2802

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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, -0.7056 in this case) is selected and presented in A3D results.