Aggrescan3D: Met847-Tyr843-Trp871 [mutate: TX847M, FX843Y, GX871W]

Project name: Met847-Tyr843-Trp871 [mutate: TX847M, FX843Y, GX871W]

Status: done

submitted: 2019-01-30 09:46:00, status changed: 2019-01-30 12:07:51

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Chain sequence(s)	X: EVTIKVNLIFADGKIQTAEFKGTFEEATAEAYRYADLLAKVNGEYTADLEDGGNHMNIKFA
Distance of aggregation	10 Å
Dynamic mode	Yes
Mutated residues	TX847M, FX843Y, GX871W
Energy difference between WT (input) and mutated protein (by FoldX)	-1.43553 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: -2.6251
Maximal score value: 0.8011
Average score: -0.6349
Total score value: -38.0959

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	-1.3019
821	V	X	0.1129
822	T	X	-0.9623
823	I	X	0.0000
824	K	X	-1.8197
825	V	X	0.0000
826	N	X	-0.7526
827	L	X	0.0000
828	I	X	0.5511
829	F	X	0.0088
830	A	X	-0.9397
831	D	X	-2.0107
832	G	X	-1.5355
833	K	X	-1.3371
834	I	X	0.7763
835	Q	X	0.0478
836	T	X	-0.6139
837	A	X	-1.2917
838	E	X	-2.6251
839	F	X	-1.8218
840	K	X	-2.6036
841	G	X	-1.7165
842	T	X	-1.2489
843	Y	X	-0.6729	mutated: FX843Y
844	E	X	-2.2602
845	E	X	-2.4919
846	A	X	0.0000
847	M	X	-0.6497	mutated: TX847M
848	A	X	-0.7607
849	E	X	-1.3904
850	A	X	0.0000
851	Y	X	0.5246
852	R	X	-0.6451
853	Y	X	0.0623
854	A	X	0.1394
855	D	X	-0.6096
856	L	X	0.8011
857	L	X	0.3333
858	A	X	-0.6413
859	K	X	-1.0097
860	V	X	0.6163
861	N	X	-1.1169
862	G	X	-0.9156
863	E	X	-1.4542
864	Y	X	0.1683
865	T	X	0.0618
866	A	X	-0.0745
867	D	X	-0.4918
868	L	X	0.2793
869	E	X	-1.1978
870	D	X	-1.5481
871	W	X	-0.1513	mutated: GX871W
872	G	X	-0.4013
873	N	X	-0.4211
874	H	X	-1.1483
875	M	X	0.0000
876	N	X	0.0000
877	I	X	0.0000
878	K	X	-0.1752
879	F	X	0.2294

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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, -0.6349 in this case) is selected and presented in A3D results.