Aggrescan3D: 20190215h8C12-4 [mutate: AH98L, SH149I, EH178A]

Project name: 20190215h8C12-4 [mutate: AH98L, SH149I, EH178A]

Status: done

submitted: 2019-02-15 03:25:59, status changed: 2019-02-15 05:51:50

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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)	-3.48568 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: -2.0499
Maximal score value: 1.911
Average score: -0.1985
Total score value: -45.6458

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	-1.0170
2	V	H	1.0520
3	Q	H	0.0484
4	L	H	0.0000
5	Q	H	-0.4790
6	E	H	0.0000
7	S	H	-0.1235
8	G	H	-0.1393
9	P	H	-0.2885
10	G	H	0.1200
11	L	H	1.6651
12	V	H	0.6763
13	K	H	-1.5902
14	P	H	-0.4607
15	S	H	-0.5840
16	E	H	-1.8663
17	T	H	-0.3816
18	L	H	0.0000
19	S	H	-0.2934
20	L	H	0.0000
21	T	H	-0.0345
22	C	H	0.0000
23	T	H	0.0232
24	V	H	0.1529
25	S	H	-0.2499
26	G	H	-0.4123
27	F	H	0.4114
28	S	H	-0.1268
29	L	H	0.0000
30	N	H	-1.3109
31	S	H	-0.4397
32	F	H	0.0000
33	G	H	0.0000
34	W	H	0.0000
35	S	H	0.0000
36	W	H	0.0000
37	I	H	0.0000
38	R	H	0.0000
39	Q	H	0.0000
40	P	H	0.0000
41	P	H	-0.2976
42	G	H	-0.5607
43	K	H	-0.4297
44	G	H	0.0000
45	L	H	0.0000
46	E	H	0.0000
47	W	H	0.0000
48	I	H	0.0000
49	G	H	0.0931
50	Y	H	0.0000
51	I	H	0.0000
52	W	H	0.2923
53	A	H	-0.1726
54	G	H	-0.7625
55	K	H	-1.9426
56	N	H	-1.5910
57	T	H	-0.4328
58	N	H	-0.7722
59	Y	H	1.0962
60	N	H	0.0563
61	P	H	-0.4160
62	S	H	-0.2402
63	L	H	0.0000
64	K	H	-1.6885
65	S	H	-0.6747
66	R	H	-1.2423
67	V	H	0.0915
68	T	H	-0.0371
69	I	H	0.1903
70	S	H	0.0096
71	V	H	0.0082
72	D	H	-1.3750
73	T	H	-0.3489
74	S	H	-0.5638
75	K	H	-1.8637
76	N	H	-1.0304
77	Q	H	-0.4363
78	F	H	0.0000
79	S	H	-0.0803
80	L	H	0.0000
81	K	H	-0.9370
82	L	H	0.0000
83	S	H	-0.0401
84	S	H	0.0140
85	V	H	0.3735
86	T	H	0.0097
87	A	H	-0.0302
88	A	H	0.0270
89	D	H	-0.2711
90	T	H	0.0000
91	A	H	0.0000
92	V	H	0.4088
93	Y	H	0.0000
94	Y	H	0.0000
95	C	H	0.0000
96	A	H	0.0000
97	R	H	0.0000
98	L	H	0.0000	mutated: AH98L
99	G	H	0.1294
100	Y	H	1.2145
101	G	H	-0.2329
102	N	H	0.0000
103	S	H	0.0000
104	L	H	0.0000
105	D	H	-1.7496
106	Y	H	-0.1227
107	W	H	0.0000
108	G	H	0.0000
109	Q	H	-0.7791
110	G	H	-0.5960
111	T	H	-0.1092
112	T	H	-0.0146
113	L	H	0.0000
114	T	H	0.0116
115	V	H	0.3922
116	S	H	-0.2576
117	S	H	-0.5683
118	D	H	-1.7305
119	I	H	0.5987
120	V	H	1.9110
121	M	H	0.4529
122	T	H	-0.0768
123	Q	H	-0.1893
124	S	H	-0.1429
125	P	H	-0.2500
126	D	H	-0.3851
127	S	H	-0.2225
128	L	H	0.2532
129	A	H	0.1566
130	V	H	0.2049
131	S	H	0.0811
132	L	H	1.4273
133	G	H	-0.3628
134	E	H	-1.4683
135	R	H	-2.0499
136	A	H	0.0000
137	T	H	-0.0381
138	I	H	0.0000
139	N	H	-0.6920
140	C	H	0.0000
141	K	H	-0.9888
142	S	H	0.0000
143	S	H	-0.2129
144	Q	H	0.0000
145	S	H	-0.1909
146	L	H	0.0000
147	L	H	0.2702
148	N	H	-0.1275
149	I	H	1.5205	mutated: SH149I
150	G	H	-0.3255
151	N	H	-1.3596
152	Q	H	-1.3236
153	R	H	-0.9961
154	N	H	-0.2772
155	Y	H	0.4849
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	0.0000
162	K	H	-0.7551
163	P	H	-0.4814
164	G	H	-0.7494
165	Q	H	-1.3038
166	P	H	-0.3152
167	P	H	-0.4172
168	K	H	-1.5955
169	L	H	0.2820
170	L	H	0.0000
171	I	H	0.0000
172	Y	H	0.6636
173	W	H	0.8635
174	A	H	0.0000
175	S	H	-0.1421
176	T	H	-0.4140
177	R	H	-1.8518
178	A	H	-0.4229	mutated: EH178A
179	S	H	-0.2723
180	G	H	-0.3225
181	V	H	0.1642
182	P	H	-0.3442
183	D	H	-0.9510
184	R	H	-0.6853
185	F	H	0.0972
186	S	H	-0.0208
187	G	H	0.0000
188	S	H	-0.2406
189	G	H	-0.2837
190	S	H	-0.3237
191	G	H	-0.4333
192	T	H	-0.1886
193	D	H	-0.2263
194	F	H	0.0000
195	T	H	-0.0467
196	L	H	0.0000
197	T	H	-0.0221
198	I	H	0.0000
199	S	H	-0.2741
200	S	H	-0.0899
201	L	H	0.0000
202	Q	H	-1.0347
203	A	H	-0.4858
204	E	H	-1.9236
205	D	H	-0.8817
206	V	H	0.2407
207	A	H	0.0000
208	V	H	0.0000
209	Y	H	0.0000
210	Y	H	0.0000
211	C	H	0.0000
212	Q	H	0.0000
213	N	H	0.0000
214	N	H	0.0000
215	Y	H	1.0147
216	Y	H	1.5272
217	F	H	0.7063
218	P	H	-0.1101
219	L	H	0.0000
220	T	H	-0.0223
221	F	H	0.0000
222	G	H	0.0000
223	T	H	0.0000
224	G	H	0.0000
225	T	H	0.0000
226	K	H	-0.5319
227	L	H	0.0000
228	E	H	-1.3952
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, -0.1985 in this case) is selected and presented in A3D results.