Project name: survivor [mutate: VC122K]

Status: done

submitted: 2019-10-12 09:29:51, status changed: 2019-10-12 11:55:37
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Chain sequence(s) C: LKFNQLKFRKKKLKFCKSHIHDWGLFAMEPIAADEMVIEYVGQNIRQVIADMREKRYEDEGIGSSYMFRVDHDTIIDATKCGNFARFINHSCNPNCYAKVITVESQKKIVIYSKQHINVNEEITYDYKFPIEDVKIPCLCGSENCRGTLN
Distance of aggregation 10 Å
Dynamic mode Yes
Mutated residues VC122K
Energy difference between WT (input) and mutated protein (by FoldX) -0.112084 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
-4.5169
Maximal score value
1.445
Average score
-0.8186
Total score value
-122.7872

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 0.4160
5 K C -0.6977
6 F C -0.5676
7 N C -1.4205
8 Q C -1.5621
9 L C 0.0000
10 K C -2.3182
11 F C -0.8132
12 R C -2.8433
13 K C -2.8712
14 K C 0.0000
15 K C -1.9314
16 L C -1.0015
17 K C -1.1255
18 F C -0.1340
19 C C -0.8266
20 K C -1.7110
21 S C -1.1700
22 H C -0.8461
23 I C 0.7329
24 H C -0.4842
25 D C -0.8686
26 W C 0.0000
27 G C 0.0000
28 L C 0.0000
29 F C -0.1427
30 A C 0.0000
31 M C -1.5773
32 E C -2.1812
33 P C -1.2651
34 I C -0.0018
35 A C -0.2553
36 A C -0.6003
37 D C -0.8147
38 E C 0.0000
39 M C -0.3147
40 V C 0.0000
41 I C -0.8718
42 E C -1.4806
43 Y C 0.0000
44 V C 0.0000
45 G C -1.6215
46 Q C -1.7151
47 N C -1.6429
48 I C 0.0000
49 R C -1.9879
50 Q C -0.7265
51 V C 1.4450
52 I C 1.0007
53 A C 0.0000
54 D C -0.6922
55 M C -0.0817
56 R C -1.3702
57 E C -2.2353
58 K C -4.0146
59 R C -4.2140
60 Y C -2.9840
61 E C -4.1115
62 D C -4.5169
63 E C -3.7409
64 G C -1.6070
65 I C 0.1826
66 G C 0.0218
67 S C 0.2208
68 S C 0.1307
69 Y C -0.1051
70 M C 0.1050
71 F C 0.0000
72 R C -1.8413
73 V C -0.6969
74 D C -1.8337
75 H C -2.2959
76 D C -2.3024
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 -1.0454
83 K C -2.0484
84 C C 0.0000
85 G C -1.4619
86 N C -1.5667
87 F C 0.0000
88 A C -1.1151
89 R C -0.9768
90 F C 0.0000
91 I C 0.0000
92 N C -0.4831
93 H C -0.3220
94 S C 0.0000
95 C C -0.7205
96 N C -0.7625
97 P C -1.0368
98 N C -1.2165
99 C C -0.5939
100 Y C 0.0807
101 A C 0.0000
102 K C -0.4645
103 V C 0.0000
104 I C 1.0934
105 T C 0.4295
106 V C 0.2868
107 E C -1.3505
108 S C -1.2582
109 Q C -1.3514
110 K C -0.7917
111 K C -0.5269
112 I C 0.0000
113 V C 0.1384
114 I C 0.0000
115 Y C 0.1695
116 S C 0.0000
117 K C -1.1882
118 Q C -1.8397
119 H C -1.4930
120 I C -0.8947
121 N C -1.8106
122 K C -2.3879 mutated: VC122K
123 N C -1.2731
124 E C 0.0000
125 E C -0.7248
126 I C 0.0000
127 T C -0.3810
128 Y C 0.0000
129 D C 0.0000
130 Y C 0.0000
131 K C -1.2369
132 F C -0.6384
133 P C -0.8518
134 I C -0.8744
135 E C -2.3985
136 D C -2.5070
137 V C -0.8521
138 K C -1.4783
139 I C 0.3318
140 P C 0.0664
141 C C 0.7807
142 L C 1.2392
143 C C 0.3534
144 G C -0.6788
145 S C -1.5298
146 E C -2.5517
147 N C -2.2202
148 C C -1.1646
149 R C -1.4255
150 G C 0.0000
151 T C -0.2550
152 L C 0.0000
153 N C -1.2280

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, -0.8186 in this case) is selected and presented in A3D results.


 

Laboratory of Theory of Biopolymers 2015