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

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

Status: done

submitted: 2019-01-30 09:25:07, status changed: 2019-01-30 11:45:12

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Chain sequence(s)	X: EVTIKVNLIFADGKIQTAEFKGTFEEATAEAYRYADLLAKVNGEYTADLEDGGNHMNIKFA
Distance of aggregation	10 Å
Dynamic mode	Yes
Mutated residues	TX847M, AX848R
Energy difference between WT (input) and mutated protein (by FoldX)	-2.33227 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: -2.9717
Maximal score value: 0.9651
Average score: -0.8446
Total score value: -50.6764

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	-1.5618
821	V	X	-0.6562
822	T	X	-1.0329
823	I	X	0.0000
824	K	X	-1.6439
825	V	X	0.0000
826	N	X	-0.9024
827	L	X	0.0000
828	I	X	0.5169
829	F	X	-0.0227
830	A	X	-0.6907
831	D	X	-1.8626
832	G	X	-1.2650
833	K	X	-0.8351
834	I	X	0.9651
835	Q	X	0.1065
836	T	X	-0.3962
837	A	X	-0.8701
838	E	X	-1.7944
839	F	X	-1.1235
840	K	X	-2.0506
841	G	X	-1.5447
842	T	X	-1.0123
843	F	X	-0.2879
844	E	X	-2.1737
845	E	X	-2.7233
846	A	X	0.0000
847	M	X	-1.1091	mutated: TX847M
848	R	X	-2.3422	mutated: AX848R
849	E	X	-1.9866
850	A	X	0.0000
851	Y	X	-0.1167
852	R	X	-1.4853
853	Y	X	-0.0613
854	A	X	0.0761
855	D	X	-0.5700
856	L	X	0.8241
857	L	X	0.4030
858	A	X	-0.4429
859	K	X	-1.0560
860	V	X	0.7771
861	N	X	-0.9254
862	G	X	-0.7632
863	E	X	-1.3061
864	Y	X	0.1941
865	T	X	-0.2659
866	A	X	-0.4189
867	D	X	-1.1711
868	L	X	-0.8538
869	E	X	-2.6552
870	D	X	-2.9717
871	G	X	-2.1066
872	G	X	-1.6669
873	N	X	-1.8825
874	H	X	-2.1302
875	M	X	0.0000
876	N	X	-1.1707
877	I	X	0.0000
878	K	X	-0.7591
879	F	X	0.1281

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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, -0.8446 in this case) is selected and presented in A3D results.