Aggrescan3D: 20190214h8C12 [mutate: SL32I, EL61A, AL211L]

Project name: 20190214h8C12 [mutate: SL32I, EL61A, AL211L]

Status: done

submitted: 2019-02-15 02:27:30, status changed: 2019-02-15 04:54:03

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Chain sequence(s)	L: DIVMTQSPDSLAVSLGERATINCKSSQSLLNSGNQRNYLTWYQQKPGQPPKLLIYWASTRESGVPDRFSGSGSGTDFTLTISSLQAEDVAVYYCQNNYYFPLTFGTGTKLEIKQVQLQESGPGLVKPSETLSLTCTVSGFSLNSFGWSWIRQPPGKGLEWIGYIWAGKNTNYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCARAGYGNSLDYWGQGTTLTVSS
Distance of aggregation	5 Å
Dynamic mode	Yes
Mutated residues	SL32I, EL61A, AL211L
Energy difference between WT (input) and mutated protein (by FoldX)	-0.742607 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: -2.078
Maximal score value: 1.7587
Average score: -0.198
Total score value: -45.5306

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	D	L	-1.7328
2	I	L	0.3082
3	V	L	1.7587
4	M	L	0.0000
5	T	L	-0.0616
6	Q	L	0.0000
7	S	L	-0.0836
8	P	L	-0.4681
9	D	L	-1.2356
10	S	L	-0.3931
11	L	L	0.1955
12	A	L	0.1016
13	V	L	0.0000
14	S	L	0.2065
15	L	L	1.4599
16	G	L	-0.3497
17	E	L	-1.6637
18	R	L	-2.0780
19	A	L	0.0000
20	T	L	-0.0584
21	I	L	0.0000
22	N	L	-0.4780
23	C	L	0.0000
24	K	L	-1.7000
25	S	L	0.0000
26	S	L	-0.2725
27	Q	L	-0.3763
28	S	L	-0.0877
29	L	L	0.2524
30	L	L	0.4775
31	N	L	0.0000
32	I	L	1.0860	mutated: SL32I
33	G	L	-0.3323
34	N	L	-1.4180
35	Q	L	-0.5632
36	R	L	-0.3398
37	N	L	-0.2004
38	Y	L	0.1857
39	L	L	0.0000
40	T	L	0.0000
41	W	L	0.0000
42	Y	L	0.0000
43	Q	L	0.0000
44	Q	L	0.0000
45	K	L	-0.4216
46	P	L	-0.1356
47	G	L	-0.3927
48	Q	L	-1.2626
49	P	L	-0.4752
50	P	L	-0.1895
51	K	L	-0.5510
52	L	L	0.0000
53	L	L	0.0000
54	I	L	0.0000
55	Y	L	0.3465
56	W	L	0.3944
57	A	L	0.0307
58	S	L	-0.2232
59	T	L	-0.4407
60	R	L	-1.8553
61	A	L	-0.3757	mutated: EL61A
62	S	L	-0.2981
63	G	L	-0.4713
64	V	L	0.0669
65	P	L	-0.2168
66	D	L	0.0000
67	R	L	-1.8441
68	F	L	0.0000
69	S	L	-0.2114
70	G	L	-0.5038
71	S	L	-0.3438
72	G	L	-0.2835
73	S	L	-0.3966
74	G	L	-0.3332
75	T	L	-0.2812
76	D	L	-0.8717
77	F	L	-0.0109
78	T	L	-0.0073
79	L	L	0.0000
80	T	L	-0.0231
81	I	L	0.0000
82	S	L	-0.2511
83	S	L	-0.1374
84	L	L	0.0000
85	Q	L	-0.4428
86	A	L	-0.3734
87	E	L	-1.8968
88	D	L	-0.8266
89	V	L	0.0000
90	A	L	0.0000
91	V	L	0.0000
92	Y	L	0.0000
93	Y	L	0.0000
94	C	L	0.0000
95	Q	L	0.0000
96	N	L	0.0000
97	N	L	0.0000
98	Y	L	0.0000
99	Y	L	0.1475
100	F	L	0.0000
101	P	L	0.0000
102	L	L	0.0000
103	T	L	0.0000
104	F	L	0.5735
105	G	L	0.0000
106	T	L	-0.0892
107	G	L	-0.4676
108	T	L	0.0000
109	K	L	-0.8326
110	L	L	0.0000
111	E	L	-1.8199
112	I	L	0.0000
113	K	L	-1.9080
114	Q	L	-1.4934
115	V	L	0.0000
116	Q	L	-1.1983
117	L	L	0.0000
118	Q	L	-1.4256
119	E	L	-1.4997
120	S	L	-0.5392
121	G	L	-0.4761
122	P	L	-0.4120
123	G	L	-0.2535
124	L	L	1.5498
125	V	L	0.4159
126	K	L	-1.6719
127	P	L	-0.6221
128	S	L	-0.5728
129	E	L	-1.8704
130	T	L	-0.3150
131	L	L	0.4638
132	S	L	0.0868
133	L	L	0.9870
134	T	L	0.2525
135	C	L	0.1846
136	T	L	0.0887
137	V	L	0.5807
138	S	L	-0.2034
139	G	L	-0.5046
140	F	L	0.0000
141	S	L	-0.1571
142	L	L	-0.0065
143	N	L	-1.2556
144	S	L	-0.4133
145	F	L	0.0450
146	G	L	-0.0468
147	W	L	0.1031
148	S	L	0.0010
149	W	L	0.2264
150	I	L	0.5776
151	R	L	-0.3440
152	Q	L	-0.2852
153	P	L	-0.1612
154	P	L	-0.2489
155	G	L	-0.8153
156	K	L	-1.8055
157	G	L	-0.2681
158	L	L	0.4297
159	E	L	-0.4504
160	W	L	1.0974
161	I	L	0.4146
162	G	L	0.1466
163	Y	L	0.0000
164	I	L	1.2065
165	W	L	0.0000
166	A	L	-0.0256
167	G	L	-0.7775
168	K	L	-1.8118
169	N	L	-0.4473
170	T	L	0.0580
171	N	L	0.1032
172	Y	L	1.2524
173	N	L	0.0604
174	P	L	-0.1481
175	S	L	-0.0370
176	L	L	0.9861
177	K	L	0.0000
178	S	L	0.0000
179	R	L	-0.5364
180	V	L	0.0000
181	T	L	-0.0245
182	I	L	0.0000
183	S	L	-0.0521
184	V	L	0.0000
185	D	L	-1.7748
186	T	L	-0.6199
187	S	L	-0.5325
188	K	L	-1.9681
189	N	L	-1.8007
190	Q	L	-1.1112
191	F	L	1.4371
192	S	L	0.2458
193	L	L	0.3274
194	K	L	-1.2945
195	L	L	1.2306
196	S	L	0.2162
197	S	L	-0.1719
198	V	L	0.2008
199	T	L	0.0186
200	A	L	0.0614
201	A	L	-0.2455
202	D	L	-1.5776
203	T	L	0.0000
204	A	L	0.2262
205	V	L	0.0000
206	Y	L	1.3402
207	Y	L	0.4470
208	C	L	0.1359
209	A	L	0.0000
210	R	L	-0.1806
211	L	L	0.0000	mutated: AL211L
212	G	L	-0.0253
213	Y	L	0.0305
214	G	L	-0.6543
215	N	L	-1.3725
216	S	L	-0.1656
217	L	L	1.1521
218	D	L	-1.4281
219	Y	L	0.0101
220	W	L	0.4564
221	G	L	-0.5855
222	Q	L	-1.3005
223	G	L	-0.3414
224	T	L	0.0598
225	T	L	0.2027
226	L	L	1.5310
227	T	L	0.5759
228	V	L	1.5224
229	S	L	0.0676
230	S	L	-0.2508

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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, -0.198 in this case) is selected and presented in A3D results.