Aggrescan3D: Therapeutic

Project name: Therapeutic_mAb

Status: done

submitted: 2019-03-08 02:23:58, status changed: 2019-03-08 04:45:16

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Chain sequence(s)	H: EVQLVESGGGLVQPGGSLRLSCAVSGYSITSGYSWNWIRQAPGKGLEWVASITYDGSTNYNPSVKGRITISRDDSKNTFYLQMNSLRAEDTAVYYCARGSHYFGHWHFAVWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKV
Distance of aggregation	10 Å
Dynamic mode	Yes

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Minimal score value: -3.3528
Maximal score value: 2.3763
Average score: -0.3583
Total score value: -78.4673

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	E	H	-1.7804
2	V	H	-0.7093
3	Q	H	-0.6978
4	L	H	0.5634
5	V	H	1.2891
6	E	H	0.1911
7	S	H	-0.1630
8	G	H	-0.4468
9	G	H	-0.4784
10	G	H	-0.3011
11	L	H	0.3014
12	V	H	-0.5732
13	Q	H	-1.2633
14	P	H	-1.0867
15	G	H	-0.9389
16	G	H	-1.1360
17	S	H	-1.3062
18	L	H	0.0000
19	R	H	-2.3146
20	L	H	0.0000
21	S	H	-0.6273
22	C	H	0.0000
23	A	H	-0.3813
24	V	H	0.0000
25	S	H	-0.5773
26	G	H	-0.8263
27	Y	H	0.3186
28	S	H	-0.1255
29	I	H	-0.0673
30	T	H	0.3263
31	S	H	-0.1846
32	G	H	0.0000
33	Y	H	0.2245
34	S	H	0.3250
35	W	H	0.0000
36	N	H	0.1365
37	W	H	0.0000
38	I	H	0.0000
39	R	H	-0.4407
40	Q	H	-0.7189
41	A	H	-0.9331
42	P	H	-1.1000
43	G	H	-1.4078
44	K	H	-1.9757
45	G	H	-1.0771
46	L	H	-0.1186
47	E	H	-0.7345
48	W	H	0.0980
49	V	H	0.0000
50	A	H	0.0000
51	S	H	-0.1036
52	I	H	0.0000
53	T	H	-0.2398
54	Y	H	0.2498
55	D	H	-1.4642
56	G	H	-1.0484
57	S	H	-0.8051
58	T	H	-0.5815
59	N	H	-0.9642
60	Y	H	-0.1825
61	N	H	-1.0152
62	P	H	-1.1392
63	S	H	-1.1012
64	V	H	-1.1512
65	K	H	-2.2143
66	G	H	-2.0121
67	R	H	-2.0206
68	I	H	-1.0089
69	T	H	-0.5527
70	I	H	-0.2449
71	S	H	-1.1107
72	R	H	-2.5519
73	D	H	-2.8741
74	D	H	-3.3528
75	S	H	-2.4217
76	K	H	-2.7371
77	N	H	0.0000
78	T	H	-1.8850
79	F	H	0.0000
80	Y	H	-0.8381
81	L	H	0.0000
82	Q	H	-1.6128
83	M	H	0.0000
84	N	H	-1.8936
85	S	H	-0.9281
86	L	H	-0.1070
87	R	H	-1.8768
88	A	H	-1.5008
89	E	H	-1.9149
90	D	H	-1.8022
91	T	H	-0.7031
92	A	H	0.0000
93	V	H	-0.0518
94	Y	H	0.0000
95	Y	H	-0.2068
96	C	H	0.0000
97	A	H	0.0000
98	R	H	0.0000
99	G	H	0.0000
100	S	H	0.0000
101	H	H	-0.1337
102	Y	H	1.5010
103	F	H	1.9079
104	G	H	0.1840
105	H	H	-0.1383
106	W	H	0.7477
107	H	H	0.3406
108	F	H	0.8082
109	A	H	0.3762
110	V	H	0.0000
111	W	H	0.7951
112	G	H	0.1387
113	Q	H	-0.7563
114	G	H	-0.4925
115	T	H	0.0000
116	L	H	0.3821
117	V	H	0.0000
118	T	H	0.0000
119	V	H	0.0000
120	S	H	0.0000
121	S	H	-1.1571
122	A	H	-0.7241
123	S	H	0.0000
124	T	H	-0.5085
125	K	H	-1.7201
126	G	H	-0.8430
127	P	H	-0.6250
128	S	H	0.1072
129	V	H	0.8165
130	F	H	1.2179
131	P	H	0.3441
132	L	H	1.1300
133	A	H	0.4722
134	P	H	-0.2893
135	S	H	-0.6513
136	S	H	-1.3945
137	K	H	-2.2166
138	S	H	-1.4416
139	T	H	-1.2309
140	S	H	-1.4779
141	G	H	-1.2917
142	G	H	-1.2420
143	T	H	-0.8577
144	A	H	-0.4416
145	A	H	0.2123
146	L	H	0.4090
147	G	H	0.0000
148	C	H	0.0000
149	L	H	0.7331
150	V	H	0.0000
151	K	H	-0.3842
152	D	H	-0.0450
153	Y	H	0.6835
154	F	H	0.3120
155	P	H	0.0000
156	E	H	-0.0539
157	P	H	-0.1690
158	V	H	0.3926
159	T	H	0.3191
160	V	H	0.7704
161	S	H	0.1776
162	W	H	0.3573
163	N	H	-0.5471
164	S	H	-0.1852
165	G	H	-0.3208
166	A	H	0.0023
167	L	H	0.1806
168	T	H	0.3196
169	S	H	0.3360
170	G	H	0.6384
171	V	H	1.6441
172	H	H	0.7435
173	T	H	1.0757
174	F	H	1.7788
175	P	H	1.0435
176	A	H	1.5112
177	V	H	2.3763
178	L	H	1.5820
179	Q	H	-0.1577
180	S	H	-0.5107
181	S	H	-0.3376
182	G	H	0.0711
183	L	H	0.7477
184	Y	H	0.9063
185	S	H	0.4849
186	L	H	1.0426
187	S	H	0.9366
188	S	H	0.0000
189	V	H	1.0210
190	V	H	0.0000
191	T	H	0.2323
192	V	H	0.0000
193	P	H	-0.4456
194	S	H	-0.3801
195	S	H	-0.3021
196	S	H	-0.1530
197	L	H	0.4447
198	G	H	-0.3563
199	T	H	-0.4738
200	Q	H	-0.7036
201	T	H	-0.3328
202	Y	H	0.0738
203	I	H	0.0107
204	C	H	0.0000
205	N	H	-1.2666
206	V	H	0.0000
207	N	H	-1.4447
208	H	H	0.0000
209	K	H	-2.1637
210	P	H	-1.3651
211	S	H	-1.6982
212	N	H	-2.3012
213	T	H	-2.1604
214	K	H	-2.6937
215	V	H	0.0000
216	D	H	-2.5740
217	K	H	0.0000
218	K	H	-1.4606
219	V	H	0.0000

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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, -0.3583 in this case) is selected and presented in A3D results.