Project name: m72e [mutate: MA72E]

Status: done

submitted: 2018-03-10 04:47:18, status changed: 2018-03-10 07:17:06
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Chain sequence(s) A: MRSGSHHHHHHRSDITSLYKKAGSAAAPFTMENLYFQSYQGNSDCYFGNGSAYRGTHSLTESGASCLPWNSMILIGKVYTAQNPSAQALGLGKHNYCRNPDGDAKPWCHVLKNRRLTWEYCDVPSCSTCGLRQYSQPQFRIKGGLFADIASHPWQAAIFAKHRRSPGERFLCGGILISSCWILSAAHCFQERFPPHHLTVILGRTYRVVPGEEEQKFEVEKYIVHKEFDDDTYDNDIALLQLKSDSSRCAQESSVVRTVCLPPADLQLPDWTECELSGYGKHEALSPFYSERLKEAHVRLYPSSRCTSQHLLNRTVTDNMLCAGDTRSGGPQANLHDACQGDSGGPLVCLNDGRMTLVGIISWGLGCGQKDVPGVYTKVTNYLDWIRDNMRP
Distance of aggregation 10 Å
Dynamic mode Yes
Mutated residues MA72E
Energy difference between WT (input) and mutated protein (by FoldX) -0.316995 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
-3.8934
Maximal score value
2.6407
Average score
-0.669
Total score value
-262.2623

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 M A 0.1154
2 R A -1.5087
3 S A -1.1547
4 G A -1.1819
5 S A -1.2099
6 H A -1.8879
7 H A -2.3995
8 H A -2.7213
9 H A -2.7550
10 H A -2.3987
11 H A -2.3518
12 R A -2.7185
13 S A -1.7408
14 D A -1.1159
15 I A 0.1453
16 T A 0.4245
17 S A 0.8797
18 L A 1.1713
19 Y A 0.8011
20 K A -0.1672
21 K A -0.5810
22 A A -0.4983
23 G A -0.7045
24 S A 0.3343
25 A A 0.0000
26 A A 0.5831
27 A A 0.7684
28 P A 0.0000
29 F A 1.6970
30 T A 0.7475
31 M A 0.6546
32 E A -0.9575
33 N A -1.0858
34 L A 0.9035
35 Y A 1.7682
36 F A 2.1650
37 Q A 0.0277
38 S A 0.5555
39 Y A 0.5995
40 Q A -1.0671
41 G A -1.0310
42 N A -1.4773
43 S A -0.8236
44 D A -0.4148
45 C A 0.5371
46 Y A 1.6043
47 F A 1.6980
48 G A -0.2780
49 N A -1.1084
50 G A 0.0000
51 S A -1.1906
52 A A 0.0000
53 Y A -1.1014
54 R A -1.6035
55 G A -1.0976
56 T A -0.4772
57 H A -0.2247
58 S A -0.0769
59 L A 0.5110
60 T A -0.0674
61 E A -1.0578
62 S A -0.9951
63 G A -0.3814
64 A A 0.0716
65 S A 0.0594
66 C A 0.0000
67 L A 0.0000
68 P A -1.0824
69 W A 0.0000
70 N A -1.6111
71 S A -0.8898
72 E A -1.4937 mutated: MA72E
73 I A -0.4113
74 L A 0.0132
75 I A 0.9019
76 G A -0.3823
77 K A -1.0167
78 V A -0.3943
79 Y A 0.0047
80 T A -0.6640
81 A A -1.1942
82 Q A -1.8715
83 N A -1.9633
84 P A -0.9606
85 S A -0.2666
86 A A 0.0000
87 Q A -0.6043
88 A A -0.1420
89 L A 0.0000
90 G A -1.1192
91 L A 0.0000
92 G A -1.9312
93 K A -2.6522
94 H A -2.2537
95 N A -1.1448
96 Y A -0.5130
97 C A 0.0000
98 R A -0.3363
99 N A 0.0000
100 P A 0.0000
101 D A -1.3842
102 G A -1.1645
103 D A -1.2769
104 A A -0.7919
105 K A 0.0000
106 P A 0.0000
107 W A 0.0000
108 C A 0.0000
109 H A 0.0000
110 V A -0.1977
111 L A -1.1724
112 K A -3.4507
113 N A -3.2581
114 R A -3.8934
115 R A -3.3969
116 L A -1.3893
117 T A -0.8819
118 W A 0.1890
119 E A -0.1131
120 Y A 0.0000
121 C A 0.0000
122 D A 0.0000
123 V A -0.3871
124 P A -0.1956
125 S A 0.0000
126 C A -0.0785
127 S A 0.0000
128 T A -0.5618
129 C A 0.0000
130 G A -0.8840
131 L A 0.0000
132 R A -2.8476
133 Q A -2.0263
134 Y A 0.0000
135 S A -1.3931
136 Q A -2.3349
137 P A -1.0365
138 Q A -0.2564
139 F A 1.0433
140 R A -0.4298
141 I A -0.5597
142 K A -1.3311
143 G A -1.2192
144 G A -0.1352
145 L A 1.2818
146 F A 1.6060
147 A A 0.2043
148 D A -1.0334
149 I A 0.0000
150 A A -0.0728
151 S A -0.7846
152 H A 0.0000
153 P A -0.4479
154 W A 0.0000
155 Q A -0.1318
156 A A 0.0000
157 A A -0.1192
158 I A 0.0000
159 F A 0.0000
160 A A 0.0000
161 K A -2.5327
162 H A -2.6990
163 R A -2.7852
164 R A -2.4926
165 S A -1.6892
166 P A -0.9965
167 G A -1.0767
168 E A -1.4869
169 R A -1.8057
170 F A 0.0000
171 L A 0.0244
172 C A 0.0000
173 G A -0.0474
174 G A 0.0000
175 I A 0.0000
176 L A 0.0000
177 I A 0.4843
178 S A 0.1895
179 S A 0.0000
180 C A 0.0000
181 W A -0.3334
182 I A 0.0000
183 L A 0.0000
184 S A 0.0000
185 A A 0.0000
186 A A 0.0000
187 H A -0.4872
188 C A 0.0000
189 F A -0.5886
190 Q A -1.1882
191 E A -1.3116
192 R A -1.4632
193 F A 0.0000
194 P A -0.9958
195 P A -0.7323
196 H A -1.6680
197 H A -2.3841
198 L A 0.0000
199 T A -1.3480
200 V A 0.0000
201 I A -1.0520
202 L A 0.0000
203 G A -1.0008
204 R A -1.0209
205 T A 0.0000
206 Y A -1.5610
207 R A -2.1191
208 V A -0.7430
209 V A 0.2503
210 P A -1.2034
211 G A -1.9519
212 E A -3.0149
213 E A -2.9498
214 E A -2.3429
215 Q A -1.8418
216 K A -2.4249
217 F A -1.8673
218 E A -2.8292
219 V A 0.0000
220 E A -2.4010
221 K A -1.2852
222 Y A 1.3906
223 I A 2.6407
224 V A 2.1703
225 H A 0.0000
226 K A -0.3592
227 E A 0.0000
228 F A -1.0611
229 D A -2.7933
230 D A -3.0684
231 D A -2.8191
232 T A -1.5442
233 Y A -0.6264
234 D A 0.0000
235 N A 0.0000
236 D A 0.0000
237 I A 0.0000
238 A A 0.0000
239 L A 0.0000
240 L A 0.0000
241 Q A -0.9313
242 L A -1.9715
243 K A -2.9801
244 S A -2.5011
245 D A -2.9280
246 S A -1.8208
247 S A -2.3601
248 R A -3.3808
249 C A -2.2896
250 A A -2.0896
251 Q A -2.5207
252 E A -2.9759
253 S A -1.6449
254 S A -1.3638
255 V A -0.2661
256 V A 0.0000
257 R A -0.7647
258 T A -0.2056
259 V A 0.0000
260 C A 0.7181
261 L A 0.0000
262 P A -0.3741
263 P A -0.9674
264 A A -0.9119
265 D A -1.6736
266 L A -0.8181
267 Q A -1.8412
268 L A -0.8176
269 P A -1.3617
270 D A -2.2825
271 W A 0.0000
272 T A -0.8213
273 E A -1.0877
274 C A 0.0000
275 E A 0.0000
276 L A 0.0000
277 S A 0.0000
278 G A 0.0000
279 Y A 0.0000
280 G A 0.0000
281 K A 0.0000
282 H A -0.7860
283 E A -1.5958
284 A A -0.5911
285 L A -0.0065
286 S A -0.5113
287 P A -0.4127
288 F A -0.1799
289 Y A -0.3741
290 S A -0.9235
291 E A -1.4418
292 R A -1.1650
293 L A 0.0000
294 K A 0.1417
295 E A 0.0115
296 A A -0.2373
297 H A -0.5633
298 V A 0.0000
299 R A -0.5631
300 L A -0.2170
301 Y A 0.0000
302 P A -0.5962
303 S A -0.6384
304 S A -0.9030
305 R A -1.4877
306 C A 0.0000
307 T A -0.5939
308 S A -0.9162
309 Q A -1.6856
310 H A 0.0000
311 L A 0.0000
312 L A 0.0697
313 N A -1.5787
314 R A -1.6929
315 T A -0.8217
316 V A -0.2609
317 T A -0.7022
318 D A -1.6679
319 N A 0.0000
320 M A -0.1222
321 L A 0.3359
322 C A 0.0000
323 A A -0.1346
324 G A 0.0000
325 D A -0.7905
326 T A -1.1311
327 R A -1.4487
328 S A -1.0604
329 G A -1.3326
330 G A -1.6052
331 P A -1.4591
332 Q A -1.7491
333 A A -1.7379
334 N A -2.0092
335 L A -1.5474
336 H A -1.3996
337 D A -1.1993
338 A A -0.4824
339 C A 0.0000
340 Q A -1.0830
341 G A 0.0000
342 D A 0.0000
343 S A 0.0000
344 G A 0.0000
345 G A 0.0000
346 P A 0.0000
347 L A 0.0000
348 V A 0.0000
349 C A 0.0000
350 L A 0.0000
351 N A -2.3383
352 D A -2.8429
353 G A -2.7744
354 R A -3.2199
355 M A 0.0000
356 T A 0.0000
357 L A 0.0000
358 V A 0.0000
359 G A 0.0000
360 I A 0.0000
361 I A 0.0000
362 S A 0.0000
363 W A 0.0000
364 G A -0.4351
365 L A -0.0562
366 G A -0.5426
367 C A -0.1471
368 G A -0.6080
369 Q A -1.4265
370 K A -2.3488
371 D A -2.1422
372 V A -1.2780
373 P A 0.0000
374 G A 0.0423
375 V A 0.0000
376 Y A 0.0000
377 T A 0.0000
378 K A -0.0828
379 V A 0.0000
380 T A 0.0000
381 N A 0.0000
382 Y A 0.0000
383 L A 0.2200
384 D A 0.0000
385 W A 0.0000
386 I A 0.3870
387 R A -0.3180
388 D A 0.0000
389 N A -0.8446
390 M A 0.0556
391 R A -0.8641
392 P A -0.6924

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, -0.669 in this case) is selected and presented in A3D results.


 

Laboratory of Theory of Biopolymers 2015