Aggrescan3D: Trp865-Arg848 [mutate: TX865W, AX848R]

Project name: Trp865-Arg848 [mutate: TX865W, AX848R]

Status: done

submitted: 2019-01-30 09:29:32, status changed: 2019-01-30 11:50:36

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Chain sequence(s)	X: EVTIKVNLIFADGKIQTAEFKGTFEEATAEAYRYADLLAKVNGEYTADLEDGGNHMNIKFA
Distance of aggregation	10 Å
Dynamic mode	Yes
Mutated residues	TX865W, AX848R
Energy difference between WT (input) and mutated protein (by FoldX)	-0.11796 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: -3.1072
Maximal score value: 1.5527
Average score: -0.6228
Total score value: -37.369

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	-1.7507
821	V	X	-0.9896
822	T	X	-1.8022
823	I	X	0.0000
824	K	X	-2.7189
825	V	X	0.0000
826	N	X	-0.8526
827	L	X	0.0000
828	I	X	0.9205
829	F	X	0.0408
830	A	X	-0.9304
831	D	X	-2.1707
832	G	X	-1.4238
833	K	X	-1.3260
834	I	X	0.7078
835	Q	X	-0.5712
836	T	X	-0.8289
837	A	X	0.0000
838	E	X	-2.6656
839	F	X	-1.5673
840	K	X	-2.0236
841	G	X	-1.1203
842	T	X	-0.1604
843	F	X	0.2167
844	E	X	-1.6617
845	E	X	-2.1675
846	A	X	-0.9803
847	T	X	-0.4766
848	R	X	0.0000	mutated: AX848R
849	E	X	-1.3673
850	A	X	0.2823
851	Y	X	1.0669
852	R	X	0.7001
853	Y	X	1.5527
854	A	X	1.1777
855	D	X	0.8181
856	L	X	0.0000
857	L	X	1.3187
858	A	X	-0.1219
859	K	X	-1.1359
860	V	X	0.5711
861	N	X	-0.4086
862	G	X	-0.6905
863	E	X	-1.0765
864	Y	X	0.8384
865	W	X	1.1672	mutated: TX865W
866	A	X	0.2109
867	D	X	-0.7206
868	L	X	-0.7662
869	E	X	-2.6617
870	D	X	-3.1072
871	G	X	-1.9129
872	G	X	-1.9685
873	N	X	-2.6881
874	H	X	-2.5536
875	M	X	0.0000
876	N	X	-0.7779
877	I	X	0.0000
878	K	X	0.4044
879	F	X	0.7824

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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, -0.6228 in this case) is selected and presented in A3D results.