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

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

Status: done

submitted: 2019-01-30 09:28:04, status changed: 2019-01-30 11:44:52

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Chain sequence(s)	X: EVTIKVNLIFADGKIQTAEFKGTFEEATAEAYRYADLLAKVNGEYTADLEDGGNHMNIKFA
Distance of aggregation	10 Å
Dynamic mode	Yes
Mutated residues	TX847M, FX843Y
Energy difference between WT (input) and mutated protein (by FoldX)	-3.0541 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: -2.9362
Maximal score value: 0.8867
Average score: -0.9072
Total score value: -54.4342

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	-1.9964
821	V	X	-0.9340
822	T	X	-1.3035
823	I	X	0.0000
824	K	X	-2.0566
825	V	X	0.0000
826	N	X	-0.7983
827	L	X	0.0000
828	I	X	0.8579
829	F	X	0.0637
830	A	X	-0.5904
831	D	X	-1.4691
832	G	X	-0.7371
833	K	X	-0.8416
834	I	X	0.8867
835	Q	X	-0.0321
836	T	X	-0.4425
837	A	X	-1.1230
838	E	X	-2.6762
839	F	X	-2.1283
840	K	X	-2.9362
841	G	X	-2.0043
842	T	X	-1.5901
843	Y	X	-0.9764	mutated: FX843Y
844	E	X	-2.4907
845	E	X	-2.8720
846	A	X	0.0000
847	M	X	0.0000	mutated: TX847M
848	A	X	-1.2338
849	E	X	-1.9673
850	A	X	0.0000
851	Y	X	-0.2019
852	R	X	-1.8078
853	Y	X	-0.7579
854	A	X	-0.5124
855	D	X	-2.1048
856	L	X	-0.6326
857	L	X	0.0000
858	A	X	-1.2451
859	K	X	-1.4888
860	V	X	0.1191
861	N	X	-1.2833
862	G	X	-0.8545
863	E	X	-1.0016
864	Y	X	0.4866
865	T	X	0.0646
866	A	X	-0.0056
867	D	X	-0.4960
868	L	X	-0.3108
869	E	X	-2.4643
870	D	X	-2.8110
871	G	X	-1.9782
872	G	X	-1.5994
873	N	X	0.0000
874	H	X	-1.9863
875	M	X	0.0000
876	N	X	-0.5510
877	I	X	0.0000
878	K	X	-0.1058
879	F	X	0.4862

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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, -0.9072 in this case) is selected and presented in A3D results.