Aggrescan3D: 20190218h8C12 [mutate: AH98L, SH149I, EH178A]

Project name: 20190218h8C12 [mutate: AH98L, SH149I, EH178A]

Status: done

submitted: 2019-02-18 04:47:32, status changed: 2019-02-18 07:15:08

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Chain sequence(s)	H: QVQLQESGPGLVKPSETLSLTCTVSGFSLNSFGWSWIRQPPGKGLEWIGYIWAGKNTNYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCARAGYGNSLDYWGQGTTLTVSSDIVMTQSPDSLAVSLGERATINCKSSQSLLNSGNQRNYLTWYQQKPGQPPKLLIYWASTRESGVPDRFSGSGSGTDFTLTISSLQAEDVAVYYCQNNYYFPLTFGTGTKLEIK
Distance of aggregation	5 Å
Dynamic mode	Yes
Mutated residues	AH98L, SH149I, EH178A
Energy difference between WT (input) and mutated protein (by FoldX)	-1.45447 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: -2.2404
Maximal score value: 2.1956
Average score: -0.1885
Total score value: -43.357

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
1	Q	H	-0.9429
2	V	H	1.2373
3	Q	H	-0.7681
4	L	H	-0.0729
5	Q	H	-1.0559
6	E	H	-1.0654
7	S	H	-0.4525
8	G	H	-0.5235
9	P	H	-0.3967
10	G	H	-0.3937
11	L	H	0.9014
12	V	H	1.5825
13	K	H	-1.4512
14	P	H	-0.5817
15	S	H	-0.1834
16	E	H	-0.4823
17	T	H	0.0240
18	L	H	0.0000
19	S	H	-0.2163
20	L	H	0.0903
21	T	H	0.0093
22	C	H	0.0000
23	T	H	-0.1293
24	V	H	0.0000
25	S	H	-0.1165
26	G	H	-0.2070
27	F	H	0.6627
28	S	H	-0.0649
29	L	H	0.0000
30	N	H	-1.3125
31	S	H	-0.3669
32	F	H	0.4763
33	G	H	-0.0212
34	W	H	0.0000
35	S	H	0.0000
36	W	H	0.0000
37	I	H	0.0000
38	R	H	-0.4737
39	Q	H	-0.5098
40	P	H	-0.1562
41	P	H	-0.3485
42	G	H	-0.6078
43	K	H	-0.6237
44	G	H	-0.2548
45	L	H	0.0000
46	E	H	-0.0891
47	W	H	0.7048
48	I	H	0.0000
49	G	H	0.0000
50	Y	H	0.1438
51	I	H	0.2798
52	W	H	0.4400
53	A	H	-0.2624
54	G	H	-0.8078
55	K	H	-1.8236
56	N	H	-0.5090
57	T	H	-0.1366
58	N	H	-0.1501
59	Y	H	0.0714
60	N	H	-0.3025
61	P	H	-0.3304
62	S	H	-0.2215
63	L	H	0.0000
64	K	H	-1.8004
65	S	H	-0.6617
66	R	H	-0.8028
67	V	H	0.0000
68	T	H	0.0063
69	I	H	0.3679
70	S	H	0.0235
71	V	H	0.4183
72	D	H	-1.1072
73	T	H	-0.3679
74	S	H	-0.5613
75	K	H	-1.8336
76	N	H	-0.8401
77	Q	H	-0.2607
78	F	H	0.0000
79	S	H	-0.0754
80	L	H	0.0000
81	K	H	-1.7053
82	L	H	0.0000
83	S	H	-0.1342
84	S	H	-0.0729
85	V	H	0.2309
86	T	H	-0.0115
87	A	H	0.0405
88	A	H	-0.2548
89	D	H	-1.7904
90	T	H	-0.4007
91	A	H	0.0924
92	V	H	0.5594
93	Y	H	0.0000
94	Y	H	0.2058
95	C	H	0.0000
96	A	H	-0.1825
97	R	H	-1.0331
98	L	H	0.0547	mutated: AH98L
99	G	H	-0.2632
100	Y	H	0.0000
101	G	H	0.0000
102	N	H	0.0000
103	S	H	0.0060
104	L	H	0.0871
105	D	H	-0.6014
106	Y	H	0.1819
107	W	H	1.1438
108	G	H	-0.4705
109	Q	H	-1.3480
110	G	H	-0.6918
111	T	H	0.0000
112	T	H	0.1989
113	L	H	1.4447
114	T	H	0.6026
115	V	H	1.7574
116	S	H	0.2427
117	S	H	-0.5563
118	D	H	-1.4894
119	I	H	2.0361
120	V	H	2.1956
121	M	H	0.6050
122	T	H	-0.0982
123	Q	H	-0.4524
124	S	H	-0.2834
125	P	H	-0.4741
126	D	H	-0.9105
127	S	H	-0.2889
128	L	H	0.6304
129	A	H	0.1802
130	V	H	0.0000
131	S	H	-0.2129
132	L	H	0.0000
133	G	H	-0.7946
134	E	H	-2.2404
135	R	H	-2.1830
136	A	H	0.0000
137	T	H	-0.0709
138	I	H	0.0000
139	N	H	-1.0804
140	C	H	0.0000
141	K	H	-1.3684
142	S	H	-0.3353
143	S	H	-0.4099
144	Q	H	-1.0819
145	S	H	-0.2541
146	L	H	0.0000
147	L	H	1.4275
148	N	H	0.3585
149	I	H	1.8562	mutated: SH149I
150	G	H	-0.2919
151	N	H	-1.4073
152	Q	H	-1.4342
153	R	H	-0.5688
154	N	H	-0.4271
155	Y	H	0.0000
156	L	H	0.0000
157	T	H	0.0000
158	W	H	0.0000
159	Y	H	0.0000
160	Q	H	0.0000
161	Q	H	-0.3273
162	K	H	-0.3224
163	P	H	-0.3850
164	G	H	-0.7365
165	Q	H	-1.3327
166	P	H	-0.4814
167	P	H	0.0000
168	K	H	-0.7096
169	L	H	0.1553
170	L	H	0.1975
171	I	H	0.0000
172	Y	H	0.0000
173	W	H	0.2636
174	A	H	0.0212
175	S	H	-0.2113
176	T	H	0.0000
177	R	H	-1.7144
178	A	H	0.0000	mutated: EH178A
179	S	H	-0.2324
180	G	H	0.0586
181	V	H	1.0448
182	P	H	-0.3585
183	D	H	-2.0149
184	R	H	-1.3278
185	F	H	0.0000
186	S	H	-0.1825
187	G	H	-0.1873
188	S	H	-0.2722
189	G	H	-0.5242
190	S	H	-0.3671
191	G	H	-0.4974
192	T	H	-0.2038
193	D	H	-0.6129
194	F	H	0.0000
195	T	H	-0.1549
196	L	H	0.0000
197	T	H	-0.0561
198	I	H	0.0000
199	S	H	-0.3026
200	S	H	-0.2266
201	L	H	0.0000
202	Q	H	-1.2595
203	A	H	-0.2838
204	E	H	-1.0903
205	D	H	-1.8406
206	V	H	-0.0041
207	A	H	0.0000
208	V	H	0.2390
209	Y	H	0.0000
210	Y	H	0.1437
211	C	H	0.0000
212	Q	H	0.0000
213	N	H	0.0000
214	N	H	0.0000
215	Y	H	0.4969
216	Y	H	1.7248
217	F	H	2.1458
218	P	H	0.2571
219	L	H	1.0366
220	T	H	0.2911
221	F	H	0.4840
222	G	H	0.0314
223	T	H	0.0000
224	G	H	-0.0858
225	T	H	0.0000
226	K	H	-0.5470
227	L	H	0.0000
228	E	H	-0.5754
229	I	H	0.0000
230	K	H	-1.7000

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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, -0.1885 in this case) is selected and presented in A3D results.