Project name: survivor [mutate: IC23E]

Status: done

submitted: 2019-10-11 12:41:51, status changed: 2019-10-11 15:11:27
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Chain sequence(s) C: LKFNQLKFRKKKLKFCKSHIHDWGLFAMEPIAADEMVIEYVGQNIRQVIADMREKRYEDEGIGSSYMFRVDHDTIIDATKCGNFARFINHSCNPNCYAKVITVESQKKIVIYSKQHINVNEEITYDYKFPIEDVKIPCLCGSENCRGTLN
Distance of aggregation 10 Å
Dynamic mode Yes
Mutated residues IC23E
Energy difference between WT (input) and mutated protein (by FoldX) -0.529919 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
-4.3837
Maximal score value
1.4547
Average score
-0.7718
Total score value
-115.7689

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 0.7126
5 K C -0.5100
6 F C -0.2934
7 N C -1.0216
8 Q C -0.4979
9 L C 0.0000
10 K C -0.8259
11 F C 0.4394
12 R C -1.1776
13 K C -1.6976
14 K C -2.6836
15 K C -2.7766
16 L C -1.3074
17 K C -1.5543
18 F C -0.2158
19 C C -0.4186
20 K C -2.1648
21 S C -2.0356
22 H C -2.7837
23 E C -3.2305 mutated: IC23E
24 H C -2.3069
25 D C -2.2751
26 W C 0.0000
27 G C -0.6055
28 L C 0.0000
29 F C -0.5362
30 A C 0.0000
31 M C -0.5727
32 E C -1.2278
33 P C -0.4194
34 I C 0.0000
35 A C 0.1049
36 A C 0.3249
37 D C -0.5626
38 E C 0.0000
39 M C 0.0000
40 V C -0.1561
41 I C 0.0000
42 E C -0.1815
43 Y C -0.3330
44 V C 0.0000
45 G C -1.6497
46 Q C -1.7970
47 N C -2.1777
48 I C 0.0000
49 R C -2.4822
50 Q C -1.7089
51 V C 0.9747
52 I C 0.7858
53 A C 0.0000
54 D C -0.9466
55 M C -0.0896
56 R C -1.6000
57 E C -2.7650
58 K C -3.9437
59 R C -3.7209
60 Y C -3.0112
61 E C -3.9511
62 D C -4.3837
63 E C -3.5859
64 G C -1.3757
65 I C 0.3390
66 G C 0.2103
67 S C -0.2387
68 S C 0.0515
69 Y C 0.0000
70 M C 0.1240
71 F C 0.0000
72 R C -1.4221
73 V C 0.0000
74 D C -1.3122
75 H C -2.0139
76 D C -2.8502
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 -1.1712
83 K C -2.1515
84 C C -1.5647
85 G C -1.4880
86 N C -1.6718
87 F C -1.1632
88 A C 0.0000
89 R C -0.4083
90 F C 0.0000
91 I C 0.3038
92 N C 0.0000
93 H C -0.0738
94 S C 0.0000
95 C C -0.5309
96 N C -1.3508
97 P C -1.4835
98 N C -1.4686
99 C C 0.0000
100 Y C -0.2237
101 A C 0.0000
102 K C -0.8795
103 V C 0.0000
104 I C 0.7193
105 T C 0.5707
106 V C 0.6614
107 E C -1.2636
108 S C -1.2216
109 Q C -1.0785
110 K C -0.7871
111 K C -0.3480
112 I C 0.0000
113 V C 0.0571
114 I C 0.0000
115 Y C -0.3187
116 S C 0.0000
117 K C -2.2106
118 Q C -2.0489
119 H C -0.7443
120 I C 1.4547
121 N C 0.0000
122 V C 1.3751
123 N C -0.2751
124 E C 0.0000
125 E C -1.6106
126 I C 0.0000
127 T C 0.0000
128 Y C 0.0000
129 D C 0.0000
130 Y C 0.0000
131 K C -0.1166
132 F C 0.6135
133 P C 0.0000
134 I C -0.1844
135 E C -1.9620
136 D C -1.8875
137 V C 0.1031
138 K C -0.4923
139 I C 0.4549
140 P C 0.0000
141 C C 0.0000
142 L C 1.1069
143 C C 0.0499
144 G C -1.7818
145 S C -2.2639
146 E C -2.9847
147 N C -2.3898
148 C C -1.5257
149 R C -2.0570
150 G C -0.8080
151 T C 0.1451
152 L C 0.3763
153 N C -0.4399

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, -0.7718 in this case) is selected and presented in A3D results.


 

Laboratory of Theory of Biopolymers 2015