Project name: survivor [mutate: FC18N, FC87D]

Status: done

submitted: 2019-10-12 09:27:24, status changed: 2019-10-12 11:56:16
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Chain sequence(s) C: LKFNQLKFRKKKLKFCKSHIHDWGLFAMEPIAADEMVIEYVGQNIRQVIADMREKRYEDEGIGSSYMFRVDHDTIIDATKCGNFARFINHSCNPNCYAKVITVESQKKIVIYSKQHINVNEEITYDYKFPIEDVKIPCLCGSENCRGTLN
Distance of aggregation 10 Å
Dynamic mode Yes
Mutated residues FC18N, FC87D
Energy difference between WT (input) and mutated protein (by FoldX) -1.5824 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.

Show buried residues

Minimal score value
-4.0074
Maximal score value
1.8948
Average score
-0.8365
Total score value
-125.4726

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 0.1206
5 K C -1.4898
6 F C -0.9265
7 N C -2.0689
8 Q C -1.7825
9 L C 0.0000
10 K C -2.5054
11 F C -0.5998
12 R C -1.5313
13 K C 0.0000
14 K C -2.9386
15 K C -2.6322
16 L C -1.2186
17 K C -2.1352
18 N C -2.1837 mutated: FC18N
19 C C -1.2929
20 K C -1.7895
21 S C -0.8996
22 H C -0.7902
23 I C 0.9175
24 H C -0.1804
25 D C -0.6896
26 W C -0.6209
27 G C -0.7719
28 L C 0.0000
29 F C -0.9108
30 A C 0.0000
31 M C -1.4388
32 E C -1.5967
33 P C -0.5988
34 I C 0.0000
35 A C -0.0744
36 A C -1.2273
37 D C -2.1896
38 E C 0.0000
39 M C 0.0000
40 V C 0.0000
41 I C 0.5763
42 E C 0.0000
43 Y C 0.3038
44 V C -0.2673
45 G C -0.7074
46 Q C -1.0106
47 N C -1.8724
48 I C 0.0000
49 R C -2.1529
50 Q C -1.1573
51 V C 1.4330
52 I C 1.4934
53 A C 0.0000
54 D C -1.1011
55 M C -0.1530
56 R C -1.4340
57 E C -2.2420
58 K C -3.7788
59 R C -4.0066
60 Y C -2.7643
61 E C -3.8110
62 D C -4.0074
63 E C -2.8167
64 G C -1.1619
65 I C -0.2452
66 G C -0.3921
67 S C -0.2291
68 S C -0.2613
69 Y C 0.1771
70 M C 0.7168
71 F C 0.9182
72 R C -1.3322
73 V C 0.0000
74 D C -2.5653
75 H C -2.7648
76 D C -2.3984
77 T C -2.1547
78 I C 0.0000
79 I C 0.0000
80 D C 0.0000
81 A C 0.0000
82 T C -1.4372
83 K C -2.5434
84 C C -1.8970
85 G C 0.0000
86 N C -2.4963
87 D C -3.0100 mutated: FC87D
88 A C -1.8662
89 R C -1.1194
90 F C 0.1443
91 I C 0.4581
92 N C 0.0000
93 H C 0.5028
94 S C 0.0000
95 C C 0.0000
96 N C -1.8777
97 P C -1.2679
98 N C -1.4554
99 C C 0.0000
100 Y C -0.0547
101 A C 0.0000
102 K C -0.2859
103 V C 0.2786
104 I C 0.6231
105 T C 0.0123
106 V C -0.2091
107 E C -1.7174
108 S C -1.3398
109 Q C -1.2438
110 K C -0.7349
111 K C -0.0102
112 I C 0.0000
113 V C 0.0000
114 I C 0.0000
115 Y C -0.7492
116 S C 0.0000
117 K C -2.6820
118 Q C -2.2550
119 H C -0.9390
120 I C 0.7942
121 N C -0.1885
122 V C 0.7722
123 N C -0.9678
124 E C 0.0000
125 E C -1.8847
126 I C 0.0000
127 T C -0.6132
128 Y C 0.0000
129 D C 0.0000
130 Y C 0.3039
131 K C -0.4468
132 F C 0.0000
133 P C -1.1652
134 I C -1.3410
135 E C -2.8825
136 D C -3.0984
137 V C 0.0000
138 K C -2.5712
139 I C -0.8273
140 P C 0.1874
141 C C 1.5502
142 L C 1.8948
143 C C 0.7577
144 G C -0.8997
145 S C -1.4651
146 E C -2.6446
147 N C -2.4945
148 C C -1.6401
149 R C -1.4407
150 G C 0.0000
151 T C 0.0000
152 L C 1.2125
153 N C 0.0131

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, -0.8365 in this case) is selected and presented in A3D results.


 

Laboratory of Theory of Biopolymers 2015