Aggrescan3D: Trp865-Met847 [mutate: TX865W, TX847M]

Project name: Trp865-Met847 [mutate: TX865W, TX847M]

Status: done

submitted: 2019-01-30 09:31:12, status changed: 2019-01-30 11:50:34

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Chain sequence(s)	X: EVTIKVNLIFADGKIQTAEFKGTFEEATAEAYRYADLLAKVNGEYTADLEDGGNHMNIKFA
Distance of aggregation	10 Å
Dynamic mode	Yes
Mutated residues	TX865W, TX847M
Energy difference between WT (input) and mutated protein (by FoldX)	-2.51251 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: -2.761
Maximal score value: 1.2534
Average score: -0.6768
Total score value: -40.6067

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	-1.4011
821	V	X	-0.1476
822	T	X	-0.6962
823	I	X	0.0000
824	K	X	-1.7743
825	V	X	0.0000
826	N	X	-1.1127
827	L	X	0.0000
828	I	X	1.2534
829	F	X	0.5909
830	A	X	-0.4565
831	D	X	-1.7643
832	G	X	-1.2185
833	K	X	-0.9357
834	I	X	1.0641
835	Q	X	0.1936
836	T	X	-0.6230
837	A	X	-1.1646
838	E	X	-1.6961
839	F	X	-0.9311
840	K	X	-1.6444
841	G	X	-1.5675
842	T	X	-0.8123
843	F	X	0.3255
844	E	X	-1.7952
845	E	X	-2.1965
846	A	X	0.0000
847	M	X	-0.3671	mutated: TX847M
848	A	X	-0.9344
849	E	X	-1.3158
850	A	X	-0.3790
851	Y	X	0.3109
852	R	X	-0.9518
853	Y	X	0.1897
854	A	X	0.2031
855	D	X	-0.4006
856	L	X	0.8376
857	L	X	0.0000
858	A	X	-0.7459
859	K	X	-0.9262
860	V	X	0.6256
861	N	X	-1.2988
862	G	X	-1.4346
863	E	X	-1.6851
864	Y	X	0.1034
865	W	X	0.7324	mutated: TX865W
866	A	X	0.1867
867	D	X	-0.9334
868	L	X	-0.5078
869	E	X	-2.2919
870	D	X	-2.7610
871	G	X	-1.9767
872	G	X	-1.6964
873	N	X	-1.8518
874	H	X	-2.2411
875	M	X	0.0000
876	N	X	-0.9569
877	I	X	0.0000
878	K	X	-0.0440
879	F	X	0.4143

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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, -0.6768 in this case) is selected and presented in A3D results.