Project name: SyxNoRhoMutants [mutate: LA251K, TA294K]

Status: done

submitted: 2018-10-15 20:11:15, status changed: 2018-11-24 16:04:06
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Chain sequence(s) A: QSNSWRELIDGHEKLTRRQCHQQEAVWELLHTEASYIRKLRVIINLFLCCLLNLQESGLLCEVEAERLFSNIPEIAQLHRRLWASVMAPVLEKARRTRALLQPGDFLKGFKMFGSLFKPYIRYCMEEEGCMEYMRGLLRDNDLFRAYITWAEKHPQCQRLKLSDMLAKPHQRLTKYPLLLKSVLRKTEEPRAKEAVVAMIGSVERFIHHVNACMRQRQERQRLAAVVSRIDAYEVVESSSDEVDKLLKEFLHLDLTAPIPGASPEETRQLLLEGSLRMKEGKDSKMDVYCFLFTDLLLVTKAVKKAERTRVIRPPLLVDKIVCRELRDPGSFLLIYLNEFHSAVGAYTFQASGQALCRGWVDTIYNAQNQLQ
Distance of aggregation 10 Å
Dynamic mode Yes
Mutated residues LA251K, TA294K
Energy difference between WT (input) and mutated protein (by FoldX) -1.64053 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
-4.0563
Maximal score value
1.5485
Average score
-1.1017
Total score value
-409.8175

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
1 Q A -1.7004
2 S A -1.8529
3 N A -2.5308
4 S A -2.1894
5 W A 0.0000
6 R A -3.1769
7 E A -3.1332
8 L A -1.4580
9 I A 0.0000
10 D A -2.6839
11 G A -2.5665
12 H A -3.3984
13 E A -3.4828
14 K A -3.6295
15 L A 0.0000
16 T A -2.8904
17 R A -3.5757
18 R A -3.2882
19 Q A -2.3619
20 C A -2.2750
21 H A -2.5446
22 Q A -1.8803
23 Q A 0.0000
24 E A -1.7351
25 A A 0.0000
26 V A -0.3914
27 W A -1.0805
28 E A -0.9816
29 L A 0.0000
30 L A 0.0000
31 H A -0.9093
32 T A -0.6277
33 E A 0.0000
34 A A -0.9511
35 S A -0.6657
36 Y A 0.0000
37 I A -1.0409
38 R A -1.4289
39 K A -1.2386
40 L A 0.0000
41 R A -1.1986
42 V A 0.0000
43 I A 0.0000
44 I A -0.2832
45 N A -0.8163
46 L A 0.0000
47 F A 0.0000
48 L A 0.2265
49 C A 0.6792
50 C A 0.0000
51 L A 0.0000
52 L A 0.3958
53 N A -0.7172
54 L A 0.0000
55 Q A -1.2141
56 E A -2.0159
57 S A -1.1530
58 G A -0.6269
59 L A 0.0301
60 L A 0.0000
61 C A 0.2948
62 E A -0.3727
63 V A 0.3957
64 E A -0.4627
65 A A 0.0000
66 E A -1.4100
67 R A -1.2671
68 L A 0.0000
69 F A 0.0000
70 S A -0.8879
71 N A 0.0000
72 I A 0.0000
73 P A -1.0316
74 E A -1.6774
75 I A 0.0000
76 A A 0.0000
77 Q A -2.6712
78 L A -1.7377
79 H A 0.0000
80 R A -3.0155
81 R A -2.7760
82 L A 0.0000
83 W A -0.7240
84 A A -0.5910
85 S A -0.5251
86 V A 0.0000
87 M A 0.0000
88 A A 0.0799
89 P A -0.5153
90 V A 0.0000
91 L A -0.2798
92 E A -2.3208
93 K A -2.3966
94 A A -2.2940
95 R A -3.3700
96 R A -3.4028
97 T A -2.7329
98 R A -2.8556
99 A A -1.7739
100 L A 0.0000
101 L A -0.7399
102 Q A -1.2976
103 P A -0.9913
104 G A 0.0000
105 D A -1.5032
106 F A 0.0000
107 L A 0.0000
108 K A -1.9593
109 G A -1.2193
110 F A 0.0000
111 K A -2.0634
112 M A -1.1232
113 F A 0.0000
114 G A -0.7929
115 S A -0.9239
116 L A 0.0000
117 F A 0.0000
118 K A -1.7692
119 P A 0.0000
120 Y A 0.0000
121 I A -0.6698
122 R A -1.4189
123 Y A 0.0000
124 C A -0.5815
125 M A -0.6342
126 E A -1.0665
127 E A -0.7761
128 E A -0.9997
129 G A -0.8813
130 C A 0.0000
131 M A -1.1248
132 E A -1.7866
133 Y A -1.0467
134 M A -1.2485
135 R A -2.6567
136 G A -2.1530
137 L A 0.0000
138 L A -2.2998
139 R A -3.6087
140 D A -3.2905
141 N A -2.3171
142 D A -2.3597
143 L A -0.6552
144 F A 0.0000
145 R A -1.8070
146 A A -0.2378
147 Y A -0.0390
148 I A 0.0000
149 T A -1.0661
150 W A -0.3570
151 A A 0.0000
152 E A -3.4705
153 K A -2.9318
154 H A -2.5283
155 P A -2.5608
156 Q A -2.8796
157 C A 0.0000
158 Q A -4.0563
159 R A -3.5453
160 L A 0.0000
161 K A -3.3157
162 L A 0.0000
163 S A -1.1561
164 D A -1.4042
165 M A -1.2288
166 L A 0.0000
167 A A -1.0618
168 K A -1.6797
169 P A 0.0000
170 H A -1.1855
171 Q A -2.0182
172 R A -1.7181
173 L A 0.0000
174 T A -1.3176
175 K A -1.6403
176 Y A 0.0000
177 P A 0.0000
178 L A 0.6316
179 L A 0.0000
180 L A 0.0000
181 K A -0.5676
182 S A -0.5852
183 V A 0.0000
184 L A -1.7876
185 R A -2.9814
186 K A -2.5149
187 T A -2.9199
188 E A -3.9443
189 E A -3.9447
190 P A -3.1076
191 R A -3.2840
192 A A -2.7360
193 K A -3.0419
194 E A -2.6315
195 A A -1.4470
196 V A 0.0000
197 V A 0.0599
198 A A -0.0079
199 M A -0.6516
200 I A 0.0000
201 G A -0.6400
202 S A -0.8455
203 V A 0.0000
204 E A -1.4498
205 R A -2.3813
206 F A -1.0845
207 I A -1.1910
208 H A -1.8579
209 H A -1.3641
210 V A 0.0000
211 N A -1.2020
212 A A -0.8523
213 C A -0.6608
214 M A -0.9346
215 R A -1.6648
216 Q A -1.9926
217 R A -2.2798
218 Q A -2.1161
219 E A 0.0000
220 R A -3.2858
221 Q A -2.2084
222 R A -1.5423
223 L A -1.5377
224 A A -0.6936
225 A A -0.4405
226 V A 0.0000
227 V A 0.0959
228 S A -0.7399
229 R A -0.9161
230 I A 0.0000
231 D A -1.6216
232 A A -1.2471
233 Y A -1.1213
234 E A -1.4622
235 V A -1.2725
236 V A -1.5343
237 E A -2.2399
238 S A -1.6248
239 S A -1.7776
240 S A -1.9614
241 D A -2.5116
242 E A -2.1471
243 V A 0.0000
244 D A -2.2513
245 K A -2.1293
246 L A 0.0000
247 L A -1.9080
248 K A -2.8025
249 E A -2.1452
250 F A 0.0000
251 K A -3.0011 mutated: LA251K
252 H A -2.1397
253 L A -0.6901
254 D A -2.2659
255 L A 0.0000
256 T A -2.1354
257 A A -1.6933
258 P A 0.0000
259 I A 0.0000
260 P A 0.0000
261 G A -0.7353
262 A A -0.3813
263 S A -0.8452
264 P A -1.4784
265 E A -2.8665
266 E A -3.4436
267 T A 0.0000
268 R A -2.6645
269 Q A -1.7597
270 L A 0.0000
271 L A -0.0638
272 L A -0.4041
273 E A -1.5932
274 G A 0.0000
275 S A -1.3911
276 L A 0.0000
277 R A -2.7014
278 M A 0.0000
279 K A -3.0892
280 E A -2.7578
281 G A -2.1255
282 K A -3.2559
283 D A -3.3721
284 S A -2.1071
285 K A -2.4300
286 M A -1.6815
287 D A -2.2513
288 V A 0.0000
289 Y A 0.0000
290 C A 0.0000
291 F A 0.0000
292 L A 0.0000
293 F A 0.0000
294 K A -0.8584 mutated: TA294K
295 D A -0.7087
296 L A 0.0000
297 L A 0.0000
298 L A 0.0000
299 V A 0.0000
300 T A 0.0000
301 K A -0.3067
302 A A -0.3232
303 V A 0.0576
304 K A -2.1526
305 K A -2.6216
306 A A 0.0000
307 E A -1.9198
308 R A -2.9497
309 T A -1.6515
310 R A 0.0000
311 V A 0.6934
312 I A 0.0000
313 R A -0.6082
314 P A -0.3914
315 P A 0.0000
316 L A 0.0000
317 L A -0.5099
318 V A 0.0000
319 D A -1.6343
320 K A -0.8327
321 I A 0.0000
322 V A 0.9842
323 C A 0.0000
324 R A -1.0010
325 E A -2.0828
326 L A -1.3796
327 R A -3.1825
328 D A -2.9106
329 P A -1.7511
330 G A 0.0000
331 S A -1.4975
332 F A 0.0000
333 L A -0.0117
334 L A 0.0000
335 I A 1.2424
336 Y A 0.0000
337 L A 0.8277
338 N A -0.1238
339 E A -0.7075
340 F A 0.6689
341 H A -0.3043
342 S A -0.1710
343 A A 0.5025
344 V A 1.5485
345 G A 0.7703
346 A A -0.0421
347 Y A 0.0000
348 T A -0.7959
349 F A 0.0000
350 Q A -1.5596
351 A A -1.0826
352 S A -0.7929
353 G A -0.9868
354 Q A -2.1311
355 A A -1.1152
356 L A -1.2230
357 C A 0.0000
358 R A -2.8684
359 G A -1.6035
360 W A 0.0000
361 V A 0.0000
362 D A -2.4187
363 T A -1.3778
364 I A 0.0000
365 Y A -1.4246
366 N A -2.1582
367 A A 0.0000
368 Q A -2.0977
369 N A -2.2330
370 Q A -1.9270
371 L A -0.8534
372 Q A -1.6522

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, -1.1017 in this case) is selected and presented in A3D results.


 

Laboratory of Theory of Biopolymers 2015