Aggrescan3D: Tyr843 [mutate: FX843Y]

Project name: Tyr843 [mutate: FX843Y]

Status: done

submitted: 2019-01-30 09:20:21, status changed: 2019-01-30 11:39:19

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Chain sequence(s)	X: EVTIKVNLIFADGKIQTAEFKGTFEEATAEAYRYADLLAKVNGEYTADLEDGGNHMNIKFA
Distance of aggregation	10 Å
Dynamic mode	Yes
Mutated residues	FX843Y
Energy difference between WT (input) and mutated protein (by FoldX)	-0.614371 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: -2.6878
Maximal score value: 0.8414
Average score: -0.9368
Total score value: -56.2093

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	-1.6070
821	V	X	-0.2436
822	T	X	-1.0132
823	I	X	0.0000
824	K	X	-1.6032
825	V	X	0.0000
826	N	X	-0.7408
827	L	X	0.0000
828	I	X	0.5011
829	F	X	0.0231
830	A	X	-0.9082
831	D	X	-1.8191
832	G	X	-1.2515
833	K	X	-1.1447
834	I	X	0.8414
835	Q	X	0.1036
836	T	X	-0.3782
837	A	X	-1.2135
838	E	X	-2.4128
839	F	X	-1.8627
840	K	X	-2.3642
841	G	X	0.0000
842	T	X	-1.0753
843	Y	X	-0.6016	mutated: FX843Y
844	E	X	-2.2101
845	E	X	-2.5506
846	A	X	0.0000
847	T	X	-0.9674
848	A	X	-1.1429
849	E	X	-1.4931
850	A	X	-0.7845
851	Y	X	0.0512
852	R	X	-1.3592
853	Y	X	-0.5936
854	A	X	-0.1524
855	D	X	-1.0034
856	L	X	-0.3058
857	L	X	0.0000
858	A	X	-1.1132
859	K	X	-1.3284
860	V	X	0.2271
861	N	X	-1.4004
862	G	X	-1.1563
863	E	X	-1.7297
864	Y	X	-0.4674
865	T	X	-0.6068
866	A	X	-0.4441
867	D	X	-0.8844
868	L	X	-0.0772
869	E	X	-1.9885
870	D	X	-2.6878
871	G	X	-2.0122
872	G	X	-1.7884
873	N	X	-1.7327
874	H	X	-1.8894
875	M	X	-1.0630
876	N	X	-1.0363
877	I	X	0.0000
878	K	X	-1.1642
879	F	X	-0.5838

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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, -0.9368 in this case) is selected and presented in A3D results.