Aggrescan3D: survivor [mutate: RC89K]

Project name: survivor [mutate: RC89K]

Status: done

submitted: 2019-10-11 13:17:40, status changed: 2019-10-11 15:46:02

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Chain sequence(s)	C: LKFNQLKFRKKKLKFCKSHIHDWGLFAMEPIAADEMVIEYVGQNIRQVIADMREKRYEDEGIGSSYMFRVDHDTIIDATKCGNFARFINHSCNPNCYAKVITVESQKKIVIYSKQHINVNEEITYDYKFPIEDVKIPCLCGSENCRGTLN
Distance of aggregation	10 Å
Dynamic mode	Yes
Mutated residues	RC89K
Energy difference between WT (input) and mutated protein (by FoldX)	-3.02476 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: -4.4172
Maximal score value: 1.9178
Average score: -0.5367
Total score value: -80.5043

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	0.2133
5	K	C	-1.1330
6	F	C	-0.4082
7	N	C	-1.2393
8	Q	C	-1.2874
9	L	C	-1.0966
10	K	C	-0.9666
11	F	C	-0.3401
12	R	C	-1.7576
13	K	C	-1.5239
14	K	C	-2.1945
15	K	C	-1.4303
16	L	C	-0.2682
17	K	C	-0.0026
18	F	C	1.5335
19	C	C	0.7093
20	K	C	-0.4318
21	S	C	-0.4996
22	H	C	-0.7505
23	I	C	0.7784
24	H	C	-0.5418
25	D	C	-0.7506
26	W	C	0.0000
27	G	C	-0.0736
28	L	C	0.0000
29	F	C	0.5805
30	A	C	0.0000
31	M	C	-0.6972
32	E	C	-0.8577
33	P	C	-0.5347
34	I	C	-0.2612
35	A	C	0.0846
36	A	C	-0.5208
37	D	C	-1.8075
38	E	C	0.0000
39	M	C	-0.2710
40	V	C	0.0000
41	I	C	0.1360
42	E	C	0.0000
43	Y	C	0.2890
44	V	C	0.0000
45	G	C	0.0000
46	Q	C	-1.7818
47	N	C	-1.5743
48	I	C	-0.5966
49	R	C	-1.4872
50	Q	C	-0.5090
51	V	C	1.7854
52	I	C	1.9178
53	A	C	0.0000
54	D	C	-0.2168
55	M	C	0.2075
56	R	C	-1.1798
57	E	C	-2.4313
58	K	C	-3.8301
59	R	C	-3.9331
60	Y	C	-3.0336
61	E	C	-4.2703
62	D	C	-4.4172
63	E	C	-3.5630
64	G	C	-1.9295
65	I	C	0.2949
66	G	C	0.2938
67	S	C	0.2183
68	S	C	0.4195
69	Y	C	0.7718
70	M	C	0.2493
71	F	C	0.0000
72	R	C	-0.6741
73	V	C	-0.2484
74	D	C	-1.1213
75	H	C	-0.9961
76	D	C	-1.3938
77	T	C	-1.4480
78	I	C	0.0000
79	I	C	0.0000
80	D	C	0.0000
81	A	C	-0.1278
82	T	C	-0.6300
83	K	C	-1.5773
84	C	C	-0.4427
85	G	C	-0.7412
86	N	C	-0.6470
87	F	C	0.9893
88	A	C	0.5452
89	K	C	0.6256	mutated: RC89K
90	F	C	0.0000
91	I	C	0.0000
92	N	C	0.0000
93	H	C	-0.2901
94	S	C	0.0000
95	C	C	-1.1933
96	N	C	-1.6230
97	P	C	-0.8985
98	N	C	-1.3711
99	C	C	0.0000
100	Y	C	-0.1135
101	A	C	0.0000
102	K	C	0.0147
103	V	C	1.1322
104	I	C	1.0641
105	T	C	0.2095
106	V	C	-0.1238
107	E	C	-1.8193
108	S	C	-1.6343
109	Q	C	-1.2903
110	K	C	0.0000
111	K	C	0.1145
112	I	C	0.0000
113	V	C	0.5018
114	I	C	0.0000
115	Y	C	-0.4770
116	S	C	-1.2588
117	K	C	-2.2334
118	Q	C	-1.8708
119	H	C	-0.1522
120	I	C	1.7055
121	N	C	1.0646
122	V	C	1.5725
123	N	C	0.1306
124	E	C	0.0000
125	E	C	-1.3003
126	I	C	0.0000
127	T	C	0.0000
128	Y	C	0.0000
129	D	C	-0.8110
130	Y	C	0.0000
131	K	C	-0.1207
132	F	C	1.1244
133	P	C	0.0195
134	I	C	-0.4255
135	E	C	-2.0634
136	D	C	-2.1022
137	V	C	-0.1887
138	K	C	-1.1769
139	I	C	0.4921
140	P	C	0.2477
141	C	C	0.9397
142	L	C	1.3727
143	C	C	-0.0410
144	G	C	-1.4969
145	S	C	-1.9202
146	E	C	-2.7627
147	N	C	-2.5933
148	C	C	-1.8567
149	R	C	-2.0643
150	G	C	0.0000
151	T	C	0.0000
152	L	C	0.0000
153	N	C	-1.1326

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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, -0.5367 in this case) is selected and presented in A3D results.