Aggrescan3D: c151_surface [mutate: VA188G, VA189G, AA190G, LA191G]

Project name: c151_surface [mutate: VA188G, VA189G, AA190G, LA191G]

Status: done

submitted: 2018-11-12 16:22:56, status changed: 2018-11-24 16:04:18

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Chain sequence(s)	A: GTVCLKYLLFTYNCCFWLAGLAVMAVGIWTLALKSDYISLLASGTYLATAYILVVAGTVVMVTGVLGCCATFKERRNLLRLYFILLLIIFLLEIIAGILAYAYYQQLNTELKENLKDTMTKRYHQPGHEAVTSAVDQLQQEFHCCGSNNSQDWRDSEWIRSQEAGGRVVPDSCCKTVVALCGQRDHASNIYKVEGGCITKLETFIQEHLRVIGAVGIGIACVQVFGMIFTCCLYR
Distance of aggregation	5 Å
Dynamic mode	Yes
Mutated residues	VA188G, VA189G, AA190G, LA191G
Energy difference between WT (input) and mutated protein (by FoldX)	-3.99858 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: -2.2115
Maximal score value: 2.4797
Average score: 0.1042
Total score value: 24.4954

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
12	G	A	-0.4791
13	T	A	0.1711
14	V	A	1.8331
15	C	A	1.2786
16	L	A	0.5665
17	K	A	-0.0531
18	Y	A	1.4757
19	L	A	0.8644
20	L	A	0.0000
21	F	A	0.7911
22	T	A	0.1944
23	Y	A	0.5081
24	N	A	0.0000
25	C	A	0.2704
26	C	A	0.6497
27	F	A	0.0000
28	W	A	0.6261
29	L	A	1.6604
30	A	A	0.3070
31	G	A	0.0000
32	L	A	1.0770
33	A	A	0.2913
34	V	A	0.4145
35	M	A	0.2887
36	A	A	0.2459
37	V	A	0.8199
38	G	A	0.0000
39	I	A	2.1398
40	W	A	1.0051
41	T	A	0.0000
42	L	A	0.8367
43	A	A	0.2230
44	L	A	0.0000
45	K	A	-1.1555
46	S	A	-0.7603
47	D	A	-1.8291
48	Y	A	0.0000
49	I	A	0.2295
50	S	A	0.1109
51	L	A	1.5104
52	L	A	0.0000
53	A	A	-0.0198
54	S	A	-0.2161
55	G	A	-0.0841
56	T	A	0.0665
57	Y	A	0.4651
58	L	A	0.0000
59	A	A	0.1423
60	T	A	0.1864
61	A	A	0.0000
62	Y	A	1.3929
63	I	A	2.4797
64	L	A	1.2511
65	V	A	0.7156
66	V	A	1.6073
67	A	A	0.2934
68	G	A	0.0000
69	T	A	-0.0073
70	V	A	0.3088
71	V	A	0.2757
72	M	A	0.4656
73	V	A	1.1000
74	T	A	0.0000
75	G	A	0.0000
76	V	A	1.5731
77	L	A	0.4840
78	G	A	0.0000
79	C	A	0.7752
80	C	A	0.4464
81	A	A	-0.1141
82	T	A	0.3742
83	F	A	1.6345
84	K	A	-1.6996
85	E	A	-2.2115
86	R	A	-1.0650
87	R	A	-2.1509
88	N	A	-1.8256
89	L	A	0.0000
90	L	A	0.0000
91	R	A	-1.7181
92	L	A	0.6589
93	Y	A	0.0000
94	F	A	1.3914
95	I	A	2.1173
96	L	A	0.4787
97	L	A	0.0000
98	L	A	1.1175
99	I	A	1.4113
100	I	A	0.0000
101	F	A	0.8357
102	L	A	1.8400
103	L	A	1.1974
104	E	A	-0.3215
105	I	A	0.9257
106	I	A	2.1412
107	A	A	0.4416
108	G	A	0.2703
109	I	A	2.0906
110	L	A	0.9631
111	A	A	0.4653
112	Y	A	1.3269
113	A	A	0.5358
114	Y	A	1.1470
115	Y	A	0.5315
116	Q	A	-1.2439
117	Q	A	-1.0216
118	L	A	-0.0303
119	N	A	-0.6643
120	T	A	-0.2626
121	E	A	-0.4871
122	L	A	0.0000
123	K	A	-1.8579
124	E	A	-1.6479
125	N	A	-0.4070
126	L	A	-0.2605
127	K	A	-1.7153
128	D	A	-0.5574
129	T	A	0.0000
130	M	A	0.7871
131	T	A	0.3287
132	K	A	0.0000
133	R	A	-0.3462
134	Y	A	0.9979
135	H	A	-0.9554
136	Q	A	-1.3906
137	P	A	-0.3654
138	G	A	-0.4117
139	H	A	-0.6227
140	E	A	-1.8631
141	A	A	-0.3251
142	V	A	0.0000
143	T	A	-0.2141
144	S	A	-0.0617
145	A	A	0.0023
146	V	A	0.0000
147	D	A	-0.3797
148	Q	A	-0.8861
149	L	A	-0.0958
150	Q	A	-0.5474
151	Q	A	-1.4726
152	E	A	-0.8930
153	F	A	0.0000
154	H	A	-0.9073
155	C	A	-0.0594
156	C	A	0.2972
157	G	A	0.0000
158	S	A	-0.2488
159	N	A	-1.5086
160	N	A	-1.5391
161	S	A	-0.3266
162	Q	A	-0.3449
163	D	A	0.0000
164	W	A	0.9198
165	R	A	-1.1773
166	D	A	0.0000
167	S	A	0.0000
168	E	A	-0.1225
169	W	A	0.5058
170	I	A	1.7139
171	R	A	-1.5198
172	S	A	-0.7937
173	Q	A	-1.5808
174	E	A	-2.0341
175	A	A	-0.3676
176	G	A	-0.5409
177	G	A	-0.7571
178	R	A	-0.8156
179	V	A	1.6390
180	V	A	1.6699
181	P	A	-0.0377
182	D	A	-1.0021
183	S	A	-0.3501
184	C	A	0.1428
185	C	A	-0.2142
186	K	A	-1.6993
187	T	A	-0.4215
188	G	A	-0.2571	mutated: VA188G
189	G	A	-0.5068	mutated: VA189G
190	G	A	-0.2227	mutated: AA190G
191	G	A	-0.5157	mutated: LA191G
192	C	A	-0.0631
193	G	A	-0.7222
194	Q	A	-1.2831
195	R	A	0.0000
196	D	A	-0.8444
197	H	A	-0.6744
198	A	A	-0.0567
199	S	A	-0.1497
200	N	A	0.0000
201	I	A	2.2570
202	Y	A	1.5486
203	K	A	-0.2285
204	V	A	1.1710
205	E	A	-0.5234
206	G	A	-0.2872
207	G	A	-0.2779
208	C	A	1.0371
209	I	A	2.1361
210	T	A	0.2381
211	K	A	-0.1868
212	L	A	0.0000
213	E	A	-1.8245
214	T	A	-0.3786
215	F	A	0.0000
216	I	A	0.0000
217	Q	A	-1.1089
218	E	A	-2.0312
219	H	A	-0.4477
220	L	A	-0.0825
221	R	A	-1.5373
222	V	A	1.4734
223	I	A	2.0284
224	G	A	0.1466
225	A	A	0.7249
226	V	A	1.9346
227	G	A	0.5774
228	I	A	1.9279
229	G	A	0.2491
230	I	A	1.4451
231	A	A	0.0000
232	C	A	0.3763
233	V	A	0.7140
234	Q	A	0.0000
235	V	A	1.1203
236	F	A	2.2396
237	G	A	0.0000
238	M	A	0.4629
239	I	A	1.7345
240	F	A	0.5944
241	T	A	0.0000
242	C	A	0.6768
243	C	A	0.5957
244	L	A	0.0000
245	Y	A	0.6950
246	R	A	-1.6516

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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, 0.1042 in this case) is selected and presented in A3D results.