Aggrescan3D: TRFI2P [mutate: DA357V, DA367V, GA386D, RA392W]

Project name: TRFI2P [mutate: DA357V, DA367V, GA386D, RA392W]

Status: done

submitted: 2018-12-19 14:15:10, status changed: 2018-12-19 16:35:44

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Chain sequence(s)	A: GAAIKIIRQLMEKFNLDLSTVTQAFLKNSGELEATSAFLASGQRADGYPIWSRQDDIDLQKDDEDTREALVKKFGAQNVARRIEFR
Distance of aggregation	10 Å
Dynamic mode	Yes
Mutated residues	DA357V, DA367V, GA386D, RA392W
Energy difference between WT (input) and mutated protein (by FoldX)	6.74908 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: -4.4342
Maximal score value: 2.2026
Average score: -0.9058
Total score value: -77.9018

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
312	G	A	-0.3032
313	A	A	-0.3012
314	A	A	0.1386
315	I	A	0.2817
316	K	A	-1.4670
317	I	A	-0.3362
318	I	A	0.0000
319	R	A	-2.4227
320	Q	A	-2.1534
321	L	A	-1.2622
322	M	A	-1.7881
323	E	A	-2.6245
324	K	A	-2.3953
325	F	A	-0.8810
326	N	A	-1.7134
327	L	A	-0.4616
328	D	A	-1.0353
329	L	A	-0.6657
330	S	A	-0.4458
331	T	A	-0.4269
332	V	A	0.0000
333	T	A	-0.5218
334	Q	A	-1.2442
335	A	A	0.0000
336	F	A	0.0000
337	L	A	-0.2299
338	K	A	-1.5651
339	N	A	0.0000
340	S	A	0.0000
341	G	A	0.0000
342	E	A	0.0000
343	L	A	-0.0583
344	E	A	-1.4192
345	A	A	0.0000
346	T	A	0.0000
347	S	A	0.2698
348	A	A	0.0000
349	F	A	1.9031
350	L	A	1.2134
351	A	A	0.7538
352	S	A	0.0838
353	G	A	-0.0532
354	Q	A	-0.9645
355	R	A	-1.0706
356	A	A	0.6165
357	V	A	1.7595	mutated: DA357V
358	G	A	0.2841
359	Y	A	0.3843
360	P	A	1.2331
361	I	A	2.2026
362	W	A	0.0000
363	S	A	-0.6107
364	R	A	-1.4359
365	Q	A	-1.6078
366	D	A	-1.1052
367	V	A	-0.2876	mutated: DA367V
368	I	A	-0.2057
369	D	A	-2.0526
370	L	A	0.0000
371	Q	A	-2.6061
372	K	A	-3.6329
373	D	A	-4.4342
374	D	A	-4.3470
375	E	A	-4.2963
376	D	A	-3.6196
377	T	A	-3.3152
378	R	A	-3.9745
379	E	A	-3.0071
380	A	A	-2.2969
381	L	A	-2.1368
382	V	A	-2.0503
383	K	A	-3.1846
384	K	A	-2.9879
385	F	A	0.0000
386	D	A	-2.9686	mutated: GA386D
387	A	A	-1.8475
388	Q	A	-1.3301
389	N	A	-1.0844
390	V	A	-0.5379
391	A	A	0.1131
392	W	A	0.3060	mutated: RA392W
393	R	A	0.0000
394	I	A	0.9977
395	E	A	-0.6176
396	F	A	0.1527
397	R	A	-1.2043

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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, -0.9058 in this case) is selected and presented in A3D results.