Aggrescan3D: Trp865-Trp871-Arg848 [mutate: AX848R, TX865W, GX871W]

Project name: Trp865-Trp871-Arg848 [mutate: AX848R, TX865W, GX871W]

Status: done

submitted: 2019-01-30 09:51:55, status changed: 2019-01-30 12:12:53

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Chain sequence(s)	X: EVTIKVNLIFADGKIQTAEFKGTFEEATAEAYRYADLLAKVNGEYTADLEDGGNHMNIKFA
Distance of aggregation	10 Å
Dynamic mode	Yes
Mutated residues	AX848R, TX865W, GX871W
Energy difference between WT (input) and mutated protein (by FoldX)	1.50443 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: -2.8458
Maximal score value: 1.3523
Average score: -0.636
Total score value: -38.1576

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	-1.5515
821	V	X	-1.0853
822	T	X	-1.2289
823	I	X	0.0000
824	K	X	-1.3185
825	V	X	0.0000
826	N	X	-0.4243
827	L	X	0.0000
828	I	X	1.2816
829	F	X	0.5249
830	A	X	-0.3495
831	D	X	-1.7658
832	G	X	-1.5371
833	K	X	-1.1637
834	I	X	1.1209
835	Q	X	0.2978
836	T	X	-0.3675
837	A	X	-1.0985
838	E	X	-1.8607
839	F	X	0.0000
840	K	X	-2.6385
841	G	X	-1.8078
842	T	X	-1.0940
843	F	X	-0.2195
844	E	X	-2.4053
845	E	X	-2.8458
846	A	X	0.0000
847	T	X	-1.8664
848	R	X	-2.8060	mutated: AX848R
849	E	X	-2.6696
850	A	X	0.0000
851	Y	X	-0.5222
852	R	X	-1.6427
853	Y	X	-0.4439
854	A	X	0.0164
855	D	X	-0.6670
856	L	X	0.6210
857	L	X	0.0000
858	A	X	-0.7952
859	K	X	-0.9470
860	V	X	0.4104
861	N	X	-1.2228
862	G	X	-0.7226
863	E	X	-1.0290
864	Y	X	0.9069
865	W	X	1.3523	mutated: TX865W
866	A	X	0.8417
867	D	X	0.3546
868	L	X	0.4224
869	E	X	-1.4622
870	D	X	-1.8109
871	W	X	-0.3685	mutated: GX871W
872	G	X	-0.7480
873	N	X	-1.0122
874	H	X	-1.0432
875	M	X	-0.5772
876	N	X	-0.1714
877	I	X	0.0000
878	K	X	0.3009
879	F	X	0.6808

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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, -0.636 in this case) is selected and presented in A3D results.