Aggrescan3D: Trp871-Arg848 [mutate: AX848R, GX871W]

Project name: Trp871-Arg848 [mutate: AX848R, GX871W]

Status: done

submitted: 2019-01-30 09:35:27, status changed: 2019-01-30 11:56:46

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Chain sequence(s)	X: EVTIKVNLIFADGKIQTAEFKGTFEEATAEAYRYADLLAKVNGEYTADLEDGGNHMNIKFA
Distance of aggregation	10 Å
Dynamic mode	Yes
Mutated residues	AX848R, GX871W
Energy difference between WT (input) and mutated protein (by FoldX)	1.70597 kcal/mol CAUTION: Your mutation/s can destabilize the protein structure 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: -2.7571
Maximal score value: 0.5121
Average score: -0.7871
Total score value: -47.2256

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	-1.3053
821	V	X	0.1105
822	T	X	-0.6844
823	I	X	-0.6703
824	K	X	-1.2919
825	V	X	0.0000
826	N	X	-0.6842
827	L	X	0.0000
828	I	X	0.2677
829	F	X	-0.0576
830	A	X	-0.7277
831	D	X	-1.9836
832	G	X	-1.4230
833	K	X	-1.3908
834	I	X	0.5121
835	Q	X	-0.5803
836	T	X	-0.5673
837	A	X	-0.8601
838	E	X	-1.5819
839	F	X	-1.3085
840	K	X	-1.9743
841	G	X	0.0000
842	T	X	-0.6886
843	F	X	-0.0315
844	E	X	-2.0654
845	E	X	-2.7571
846	A	X	0.0000
847	T	X	-1.2166
848	R	X	-2.1690	mutated: AX848R
849	E	X	-1.9308
850	A	X	-0.8249
851	Y	X	-0.3443
852	R	X	-1.7390
853	Y	X	0.0000
854	A	X	-0.4079
855	D	X	-1.1263
856	L	X	-0.1746
857	L	X	-0.0396
858	A	X	-0.9896
859	K	X	-1.2394
860	V	X	0.2472
861	N	X	-1.3376
862	G	X	-0.9653
863	E	X	-1.2891
864	Y	X	-0.0438
865	T	X	-0.3184
866	A	X	-0.5818
867	D	X	-1.1801
868	L	X	-0.0273
869	E	X	-1.2689
870	D	X	-1.5309
871	W	X	-0.1785	mutated: GX871W
872	G	X	-0.6716
873	N	X	-0.9230
874	H	X	-1.1107
875	M	X	-0.7445
876	N	X	-0.8436
877	I	X	0.0000
878	K	X	-0.5320
879	F	X	0.0198

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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, -0.7871 in this case) is selected and presented in A3D results.