Aggrescan3D: Met847 [mutate: TX847M]

Project name: Met847 [mutate: TX847M]

Status: done

submitted: 2019-01-30 09:15:26, status changed: 2019-01-30 11:36:07

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Chain sequence(s)	X: EVTIKVNLIFADGKIQTAEFKGTFEEATAEAYRYADLLAKVNGEYTADLEDGGNHMNIKFA
Distance of aggregation	10 Å
Dynamic mode	Yes
Mutated residues	TX847M
Energy difference between WT (input) and mutated protein (by FoldX)	-2.36576 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: -2.9883
Maximal score value: 1.2178
Average score: -0.7065
Total score value: -42.3895

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	-1.2416
821	V	X	0.6414
822	T	X	-0.6397
823	I	X	0.0000
824	K	X	-1.8433
825	V	X	0.0000
826	N	X	-0.4271
827	L	X	0.0000
828	I	X	1.2178
829	F	X	0.7930
830	A	X	-0.4116
831	D	X	-1.9328
832	G	X	-1.4169
833	K	X	-1.0765
834	I	X	1.1264
835	Q	X	0.5966
836	T	X	-0.1749
837	A	X	0.0000
838	E	X	-2.6307
839	F	X	0.0000
840	K	X	-2.3494
841	G	X	-1.3668
842	T	X	-0.3734
843	F	X	0.4192
844	E	X	-1.5715
845	E	X	-1.8614
846	A	X	0.0000
847	M	X	-0.1993	mutated: TX847M
848	A	X	-0.6069
849	E	X	-1.0151
850	A	X	0.0000
851	Y	X	0.3031
852	R	X	-1.2405
853	Y	X	-0.3535
854	A	X	-0.3128
855	D	X	-1.2866
856	L	X	-0.5417
857	L	X	0.0000
858	A	X	-1.3691
859	K	X	-1.6121
860	V	X	-0.3538
861	N	X	-1.4825
862	G	X	-0.8522
863	E	X	-1.1792
864	Y	X	0.3243
865	T	X	-0.0480
866	A	X	-0.5722
867	D	X	-1.4772
868	L	X	-0.8128
869	E	X	-2.6864
870	D	X	-2.9883
871	G	X	-1.8417
872	G	X	-0.9252
873	N	X	-1.6388
874	H	X	-2.0658
875	M	X	-1.4140
876	N	X	-0.8579
877	I	X	0.0000
878	K	X	0.1692
879	F	X	1.0707

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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, -0.7065 in this case) is selected and presented in A3D results.