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

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

Status: done

submitted: 2019-01-30 09:26:27, status changed: 2019-01-30 11:44:50

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Chain sequence(s)	X: EVTIKVNLIFADGKIQTAEFKGTFEEATAEAYRYADLLAKVNGEYTADLEDGGNHMNIKFA
Distance of aggregation	10 Å
Dynamic mode	Yes
Mutated residues	TX847M, GX871W
Energy difference between WT (input) and mutated protein (by FoldX)	-0.743362 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: -2.7673
Maximal score value: 1.7137
Average score: -0.5894
Total score value: -35.3662

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	-1.8489
821	V	X	-0.9115
822	T	X	-1.5831
823	I	X	0.0000
824	K	X	-2.2671
825	V	X	0.0000
826	N	X	-0.8011
827	L	X	0.0000
828	I	X	1.2175
829	F	X	0.7061
830	A	X	-0.1344
831	D	X	-1.7044
832	G	X	-1.0253
833	K	X	-1.0566
834	I	X	0.9348
835	Q	X	-0.4205
836	T	X	-0.8569
837	A	X	-1.4498
838	E	X	-2.7673
839	F	X	-2.0168
840	K	X	-2.6306
841	G	X	0.0000
842	T	X	-0.9586
843	F	X	0.0337
844	E	X	-1.7106
845	E	X	-2.2391
846	A	X	0.0000
847	M	X	-0.4718	mutated: TX847M
848	A	X	-0.8716
849	E	X	-1.3362
850	A	X	0.0000
851	Y	X	0.2185
852	R	X	-1.2083
853	Y	X	-0.3074
854	A	X	-0.0565
855	D	X	-0.8953
856	L	X	0.5338
857	L	X	0.0000
858	A	X	-0.8824
859	K	X	-1.0146
860	V	X	0.3198
861	N	X	-1.2470
862	G	X	-0.5814
863	E	X	-0.7471
864	Y	X	0.8080
865	T	X	0.2643
866	A	X	0.2911
867	D	X	-0.7712
868	L	X	-0.1358
869	E	X	-1.0293
870	D	X	-1.5946
871	W	X	-0.0495	mutated: GX871W
872	G	X	-0.8190
873	N	X	-0.8620
874	H	X	-1.4076
875	M	X	0.0000
876	N	X	-0.5308
877	I	X	0.0000
878	K	X	0.7945
879	F	X	1.7137

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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, -0.5894 in this case) is selected and presented in A3D results.