Aggrescan3D: survivor [mutate: FC18S]

Project name: survivor [mutate: FC18S]

Status: done

submitted: 2019-10-12 02:58:31, status changed: 2019-10-12 05:25:32

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Chain sequence(s)	C: LKFNQLKFRKKKLKFCKSHIHDWGLFAMEPIAADEMVIEYVGQNIRQVIADMREKRYEDEGIGSSYMFRVDHDTIIDATKCGNFARFINHSCNPNCYAKVITVESQKKIVIYSKQHINVNEEITYDYKFPIEDVKIPCLCGSENCRGTLN
Distance of aggregation	10 Å
Dynamic mode	Yes
Mutated residues	FC18S
Energy difference between WT (input) and mutated protein (by FoldX)	0.821993 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: -4.1179
Maximal score value: 1.2706
Average score: -0.7727
Total score value: -115.9078

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
4	L	C	0.7199
5	K	C	-1.4026
6	F	C	-0.0705
7	N	C	-1.4126
8	Q	C	-1.4172
9	L	C	0.0000
10	K	C	-1.8705
11	F	C	0.0914
12	R	C	-0.9140
13	K	C	-1.7021
14	K	C	-2.5320
15	K	C	-2.2224
16	L	C	-1.2843
17	K	C	-1.1603
18	S	C	-0.6648	mutated: FC18S
19	C	C	-0.7618
20	K	C	-1.0770
21	S	C	-0.8565
22	H	C	-0.8130
23	I	C	1.0150
24	H	C	-0.4221
25	D	C	-1.3132
26	W	C	0.0000
27	G	C	0.0000
28	L	C	0.0000
29	F	C	-0.7317
30	A	C	0.0000
31	M	C	-1.4677
32	E	C	-1.3757
33	P	C	0.0430
34	I	C	0.0000
35	A	C	-0.3089
36	A	C	-1.6159
37	D	C	-2.6277
38	E	C	0.0000
39	M	C	0.0000
40	V	C	0.5843
41	I	C	1.0017
42	E	C	0.0000
43	Y	C	0.5417
44	V	C	0.0000
45	G	C	-0.8080
46	Q	C	-1.7925
47	N	C	-2.3244
48	I	C	-1.4475
49	R	C	-2.2277
50	Q	C	-1.0977
51	V	C	1.1406
52	I	C	0.7632
53	A	C	0.0000
54	D	C	-0.9775
55	M	C	-0.0976
56	R	C	-1.2354
57	E	C	-2.3290
58	K	C	-3.6734
59	R	C	-3.3283
60	Y	C	-2.9033
61	E	C	-3.9899
62	D	C	-4.1179
63	E	C	-3.2701
64	G	C	-1.2918
65	I	C	0.8988
66	G	C	0.1415
67	S	C	-0.1663
68	S	C	-0.1996
69	Y	C	-0.0711
70	M	C	0.0643
71	F	C	-0.4033
72	R	C	-1.5778
73	V	C	0.0000
74	D	C	-1.7868
75	H	C	-2.4219
76	D	C	-2.2779
77	T	C	0.0000
78	I	C	0.0000
79	I	C	0.0000
80	D	C	0.0000
81	A	C	0.0000
82	T	C	-0.5666
83	K	C	-1.1337
84	C	C	0.0606
85	G	C	-0.3056
86	N	C	-0.3526
87	F	C	0.9946
88	A	C	0.0000
89	R	C	-0.0287
90	F	C	0.0000
91	I	C	-0.3126
92	N	C	-0.6816
93	H	C	-0.4070
94	S	C	0.0000
95	C	C	0.0000
96	N	C	-1.9551
97	P	C	-1.6389
98	N	C	-2.0720
99	C	C	0.0000
100	Y	C	-0.2531
101	A	C	0.0000
102	K	C	-0.7288
103	V	C	0.0000
104	I	C	0.3351
105	T	C	0.0000
106	V	C	0.3394
107	E	C	-1.4519
108	S	C	-0.9823
109	Q	C	-0.8706
110	K	C	0.0000
111	K	C	-0.4107
112	I	C	0.0000
113	V	C	0.0000
114	I	C	0.0000
115	Y	C	-0.6352
116	S	C	0.0000
117	K	C	-2.3886
118	Q	C	-2.2487
119	H	C	-1.1461
120	I	C	1.0173
121	N	C	-0.0067
122	V	C	0.7037
123	N	C	-0.8583
124	E	C	-0.9126
125	E	C	-1.7644
126	I	C	0.0000
127	T	C	-0.8463
128	Y	C	0.0000
129	D	C	0.0000
130	Y	C	0.0000
131	K	C	-1.7485
132	F	C	-0.9843
133	P	C	-0.9571
134	I	C	-0.9926
135	E	C	-2.3810
136	D	C	-2.8973
137	V	C	-2.1807
138	K	C	-2.4203
139	I	C	-0.8019
140	P	C	-0.2132
141	C	C	0.6418
142	L	C	1.2706
143	C	C	0.6883
144	G	C	-0.6413
145	S	C	-1.6110
146	E	C	-2.7005
147	N	C	-2.6641
148	C	C	-1.4354
149	R	C	-1.5533
150	G	C	0.0000
151	T	C	-0.0644
152	L	C	-0.5575
153	N	C	-1.3603

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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, -0.7727 in this case) is selected and presented in A3D results.