Project name: transthyretin_aggregation

Status: done

Started: 2024-04-30 16:45:20
Settings
Chain sequence(s) A: CPLMVKVLDAVRGSPAINVAVHVFRRKAADDTWEPFASGKTSESGELHGLTTEEEFVEGIYKVEEIDDTKSYWKALGISPFHEHAEVVFTANDSGPRRYTIAALLSPYSYSSTTTAVVTNP
B: CPLMVKVLDAVRGSPAINNVAVHVFRRKAADDTWEPFASGKTSESGELHGLTTEEEFVEGIYKVEIDDTKSYWKALGISPFHEHAEVVFTANDSSGGPPRRRYTIAALLSPYSYSSTTTAVVTN
input PDB
Selected Chain(s) A,B
Distance of aggregation 5 Å
FoldX usage Yes
Dynamic mode No
Automated mutations Yes
Downloads Download all the data
Simulation log 
[INFO]       Logger:   Verbosity set to: 2 - [INFO]                                                (00:00:00)
[WARNING]    runJob:   Working directory already exists (possibly overwriting previous results -ow 
                       to prevent this behavior)                                                   (00:00:00)
[INFO]       runJob:   Starting aggrescan3d job on: input.pdb with all chain(s) selected           (00:00:00)
[INFO]       runJob:   Creating pdb object from: input.pdb                                         (00:00:00)
[INFO]       FoldX:    Starting FoldX energy minimalization                                        (00:00:00)
[INFO]       Analysis: Starting Aggrescan3D on folded.pdb                                          (00:02:40)
[INFO]       Auto_mut: Residue number 121 from chain A and a score of 1.872 (valine) selected for  
                       automated muatation                                                         (00:02:42)
[INFO]       Auto_mut: Residue number 20 from chain A and a score of 1.555 (valine) selected for   
                       automated muatation                                                         (00:02:42)
[INFO]       Auto_mut: Residue number 121 from chain B and a score of 1.430 (valine) selected for  
                       automated muatation                                                         (00:02:42)
[INFO]       Auto_mut: Residue number 20 from chain B and a score of 1.151 (valine) selected for   
                       automated muatation                                                         (00:02:42)
[INFO]       Auto_mut: Residue number 65 from chain B and a score of 1.085 (valine) selected for   
                       automated muatation                                                         (00:02:42)
[INFO]       Auto_mut: Residue number 122 from chain A and a score of 0.856 (valine) selected for  
                       automated muatation                                                         (00:02:42)
[INFO]       Auto_mut: Mutating residue number 121 from chain A (valine) into glutamic acid        (00:02:42)
[INFO]       Auto_mut: Mutating residue number 121 from chain A (valine) into aspartic acid        (00:02:42)
[INFO]       Auto_mut: Mutating residue number 20 from chain A (valine) into glutamic acid         (00:02:42)
[INFO]       Auto_mut: Mutating residue number 121 from chain A (valine) into arginine             (00:04:05)
[INFO]       Auto_mut: Mutating residue number 121 from chain A (valine) into lysine               (00:04:08)
[INFO]       Auto_mut: Mutating residue number 20 from chain A (valine) into lysine                (00:04:08)
[INFO]       Auto_mut: Mutating residue number 20 from chain A (valine) into aspartic acid         (00:05:40)
[INFO]       Auto_mut: Mutating residue number 121 from chain B (valine) into glutamic acid        (00:05:44)
[INFO]       Auto_mut: Mutating residue number 121 from chain B (valine) into aspartic acid        (00:05:49)
[INFO]       Auto_mut: Mutating residue number 20 from chain A (valine) into arginine              (00:07:02)
[INFO]       Auto_mut: Mutating residue number 121 from chain B (valine) into arginine             (00:07:16)
[INFO]       Auto_mut: Mutating residue number 121 from chain B (valine) into lysine               (00:07:16)
[INFO]       Auto_mut: Mutating residue number 20 from chain B (valine) into glutamic acid         (00:08:31)
[INFO]       Auto_mut: Mutating residue number 20 from chain B (valine) into aspartic acid         (00:08:52)
[INFO]       Auto_mut: Mutating residue number 65 from chain B (valine) into glutamic acid         (00:08:57)
[INFO]       Auto_mut: Mutating residue number 20 from chain B (valine) into lysine                (00:09:57)
[INFO]       Auto_mut: Mutating residue number 20 from chain B (valine) into arginine              (00:10:14)
[INFO]       Auto_mut: Mutating residue number 65 from chain B (valine) into lysine                (00:10:24)
[INFO]       Auto_mut: Mutating residue number 65 from chain B (valine) into aspartic acid         (00:11:26)
[INFO]       Auto_mut: Mutating residue number 122 from chain A (valine) into glutamic acid        (00:11:38)
[INFO]       Auto_mut: Mutating residue number 122 from chain A (valine) into aspartic acid        (00:11:53)
[INFO]       Auto_mut: Mutating residue number 65 from chain B (valine) into arginine              (00:12:46)
[INFO]       Auto_mut: Mutating residue number 122 from chain A (valine) into lysine               (00:13:07)
[INFO]       Auto_mut: Mutating residue number 122 from chain A (valine) into arginine             (00:13:16)
[INFO]       Auto_mut: Effect of mutation residue number 121 from chain A (valine) into glutamic   
                       acid: Energy difference: 0.0643 kcal/mol, Difference in average score from  
                       the base case: -0.0146                                                      (00:14:43)
[INFO]       Auto_mut: Effect of mutation residue number 121 from chain A (valine) into lysine:    
                       Energy difference: -0.3448 kcal/mol, Difference in average score from the   
                       base case: -0.0129                                                          (00:14:43)
[INFO]       Auto_mut: Effect of mutation residue number 121 from chain A (valine) into aspartic   
                       acid: Energy difference: 0.1541 kcal/mol, Difference in average score from  
                       the base case: -0.0145                                                      (00:14:43)
[INFO]       Auto_mut: Effect of mutation residue number 121 from chain A (valine) into arginine:  
                       Energy difference: -0.6849 kcal/mol, Difference in average score from the   
                       base case: -0.0156                                                          (00:14:43)
[INFO]       Auto_mut: Effect of mutation residue number 20 from chain A (valine) into glutamic    
                       acid: Energy difference: 0.3395 kcal/mol, Difference in average score from  
                       the base case: -0.0156                                                      (00:14:43)
[INFO]       Auto_mut: Effect of mutation residue number 20 from chain A (valine) into lysine:     
                       Energy difference: -0.6558 kcal/mol, Difference in average score from the   
                       base case: -0.0157                                                          (00:14:43)
[INFO]       Auto_mut: Effect of mutation residue number 20 from chain A (valine) into aspartic    
                       acid: Energy difference: 1.2798 kcal/mol, Difference in average score from  
                       the base case: -0.0184                                                      (00:14:43)
[INFO]       Auto_mut: Effect of mutation residue number 20 from chain A (valine) into arginine:   
                       Energy difference: -0.4329 kcal/mol, Difference in average score from the   
                       base case: -0.0160                                                          (00:14:43)
[INFO]       Auto_mut: Effect of mutation residue number 121 from chain B (valine) into glutamic   
                       acid: Energy difference: -0.0033 kcal/mol, Difference in average score from 
                       the base case: -0.0114                                                      (00:14:43)
[INFO]       Auto_mut: Effect of mutation residue number 121 from chain B (valine) into lysine:    
                       Energy difference: -0.2889 kcal/mol, Difference in average score from the   
                       base case: -0.0095                                                          (00:14:43)
[INFO]       Auto_mut: Effect of mutation residue number 121 from chain B (valine) into aspartic   
                       acid: Energy difference: 0.2258 kcal/mol, Difference in average score from  
                       the base case: -0.0129                                                      (00:14:43)
[INFO]       Auto_mut: Effect of mutation residue number 121 from chain B (valine) into arginine:  
                       Energy difference: -0.3898 kcal/mol, Difference in average score from the   
                       base case: -0.0136                                                          (00:14:43)
[INFO]       Auto_mut: Effect of mutation residue number 20 from chain B (valine) into glutamic    
                       acid: Energy difference: 0.4495 kcal/mol, Difference in average score from  
                       the base case: -0.0157                                                      (00:14:43)
[INFO]       Auto_mut: Effect of mutation residue number 20 from chain B (valine) into lysine:     
                       Energy difference: -0.7067 kcal/mol, Difference in average score from the   
                       base case: -0.0159                                                          (00:14:43)
[INFO]       Auto_mut: Effect of mutation residue number 20 from chain B (valine) into aspartic    
                       acid: Energy difference: 1.4836 kcal/mol, Difference in average score from  
                       the base case: -0.0156                                                      (00:14:43)
[INFO]       Auto_mut: Effect of mutation residue number 20 from chain B (valine) into arginine:   
                       Energy difference: -0.2639 kcal/mol, Difference in average score from the   
                       base case: -0.0173                                                          (00:14:43)
[INFO]       Auto_mut: Effect of mutation residue number 65 from chain B (valine) into glutamic    
                       acid: Energy difference: -0.8243 kcal/mol, Difference in average score from 
                       the base case: -0.0153                                                      (00:14:43)
[INFO]       Auto_mut: Effect of mutation residue number 65 from chain B (valine) into lysine:     
                       Energy difference: -0.8438 kcal/mol, Difference in average score from the   
                       base case: -0.0154                                                          (00:14:43)
[INFO]       Auto_mut: Effect of mutation residue number 65 from chain B (valine) into aspartic    
                       acid: Energy difference: -1.2045 kcal/mol, Difference in average score from 
                       the base case: -0.0155                                                      (00:14:43)
[INFO]       Auto_mut: Effect of mutation residue number 65 from chain B (valine) into arginine:   
                       Energy difference: -0.8016 kcal/mol, Difference in average score from the   
                       base case: -0.0166                                                          (00:14:43)
[INFO]       Auto_mut: Effect of mutation residue number 122 from chain A (valine) into glutamic   
                       acid: Energy difference: -0.3740 kcal/mol, Difference in average score from 
                       the base case: -0.0049                                                      (00:14:43)
[INFO]       Auto_mut: Effect of mutation residue number 122 from chain A (valine) into lysine:    
                       Energy difference: 0.8060 kcal/mol, Difference in average score from the    
                       base case: -0.0053                                                          (00:14:43)
[INFO]       Auto_mut: Effect of mutation residue number 122 from chain A (valine) into aspartic   
                       acid: Energy difference: 2.6261 kcal/mol, Difference in average score from  
                       the base case: -0.0034                                                      (00:14:43)
[INFO]       Auto_mut: Effect of mutation residue number 122 from chain A (valine) into arginine:  
                       Energy difference: 1.6831 kcal/mol, Difference in average score from the    
                       base case: -0.0038                                                          (00:14:43)
[INFO]       Main:     Simulation completed successfully.                                          (00:14:48)
Show buried residues
Minimal score value
-2.4408
Maximal score value
1.8718
Average score
-0.2718
Total score value
-62.7968
Download the table (csv)

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
10 C A 0.4924
11 P A 0.0000
12 L A 0.0000
13 M A 0.1222
14 V A 0.0000
15 K A -0.6533
16 V A 0.0000
17 L A 0.3908
18 D A 0.0000
19 A A 0.3861
20 V A 1.5546
21 R A -1.0074
22 G A -0.7052
23 S A -0.1618
24 P A -0.0462
25 A A 0.0000
26 I A 0.3036
27 N A -1.1736
28 V A 0.0000
29 A A -0.2121
30 V A 0.0000
31 H A -0.3597
32 V A 0.0000
33 F A 0.1995
34 R A -0.4319
35 K A -0.4644
36 A A -0.0568
37 A A -0.2689
38 D A -2.1068
39 D A -2.1298
40 T A -0.3214
41 W A 0.0848
42 E A -1.3535
43 P A -0.4201
44 F A 0.2799
45 A A 0.0226
46 S A -0.2787
47 G A -0.4685
48 K A -1.7186
49 T A 0.0000
50 S A -0.4303
51 E A -1.8718
52 S A -0.5219
53 G A 0.0000
54 E A -0.3468
55 L A 0.0000
56 H A -1.0764
57 G A -0.6495
58 L A 0.0000
59 T A 0.0000
60 T A -0.3892
61 E A -2.1631
62 E A -2.4255
63 E A -1.8006
64 F A 0.0000
65 V A 0.5499
66 E A -1.6696
67 G A -0.3081
68 I A 0.5437
69 Y A 0.0000
70 K A 0.0000
71 V A 0.0000
72 E A -0.3893
73 I A 0.0000
74 D A -0.4605
75 T A 0.0000
76 K A -0.6430
77 S A -0.2956
78 Y A 0.0000
79 W A 0.0000
80 K A -1.6349
81 A A -0.1033
82 L A 0.7451
83 G A -0.2189
84 I A 0.2270
85 S A -0.1215
86 P A -0.0784
87 F A 0.0000
88 H A 0.0000
89 E A -0.2213
90 H A -0.2372
91 A A 0.0000
92 E A 0.0000
93 V A 0.0000
94 V A 0.0000
95 F A 0.0000
96 T A 0.0532
97 A A 0.0000
98 N A 0.0000
99 D A -1.8285
100 S A -0.5739
101 G A -0.2627
102 P A -0.3898
103 R A -0.9181
104 R A -1.1574
105 Y A 0.0000
106 T A 0.0006
107 I A 0.0000
108 A A -0.0657
109 A A 0.0000
110 L A 0.8003
111 L A 0.0000
112 S A -0.0582
113 P A 0.0524
114 Y A 0.6027
115 S A 0.0760
116 Y A 0.0000
117 S A -0.0576
118 T A 0.0000
119 T A -0.0328
120 A A 0.0000
121 V A 1.8718
122 V A 0.8558
123 T A -0.1788
124 N A -1.3826
125 P A -0.4876
10 C B 0.7316
11 P B 0.0000
12 L B 0.0000
13 M B 0.1087
14 V B 0.0000
15 K B -0.6322
16 V B 0.0000
17 L B 0.3876
18 D B 0.0000
19 A B 0.3215
20 V B 1.1515
21 R B -1.3891
22 G B -0.7613
23 S B -0.1396
24 P B -0.0449
25 A B 0.0000
26 I B 0.5020
27 N B -1.1345
28 V B 0.0000
29 A B -0.1760
30 V B 0.0000
31 H B -0.6467
32 V B 0.0000
33 F B 0.1508
34 R B -0.5113
35 K B -0.4595
36 A B -0.0525
37 A B -0.2682
38 D B -2.1069
39 D B -2.1300
40 T B -0.3369
41 W B -0.0638
42 E B -1.7692
43 P B -0.4999
44 F B 0.2603
45 A B 0.0210
46 S B -0.3229
47 G B -0.4155
48 K B -1.3602
49 T B 0.0000
50 S B -0.4267
51 E B -1.8671
52 S B -0.5018
53 G B 0.0000
54 E B -0.3027
55 L B -0.0810
56 H B -1.0478
57 G B -0.6216
58 L B 0.0631
59 T B 0.0000
60 T B -0.3959
61 E B -2.1657
62 E B -2.4408
63 E B -1.8312
64 F B 0.1640
65 V B 1.0855
66 E B -1.5786
67 G B -0.3194
68 I B 0.5316
69 Y B 0.0000
70 K B 0.0000
71 V B 0.0000
72 E B -0.2746
73 I B 0.0000
74 D B -0.5712
75 T B 0.0000
76 K B -0.6318
77 S B -0.2849
78 Y B 0.0000
79 W B 0.0000
80 K B -1.7379
81 A B -0.1456
82 L B 0.5184
83 G B -0.4240
84 I B 0.4759
85 S B -0.1095
86 P B -0.0808
87 F B 0.0000
88 H B 0.0000
89 E B -0.2497
90 H B -0.2545
91 A B 0.0000
92 E B 0.0000
93 V B 0.0000
94 V B 0.0000
95 F B 0.0000
96 T B 0.0431
97 A B 0.0000
98 N B -1.2579
99 D B -2.0003
100 S B -0.5698
101 G B -0.1950
102 P B -0.6062
103 R B -2.0359
104 R B -1.3170
105 Y B 0.0000
106 T B 0.0000
107 I B 0.0000
108 A B -0.0648
109 A B 0.0000
110 L B 0.8362
111 L B 0.0000
112 S B -0.0634
113 P B 0.0579
114 Y B 0.6076
115 S B 0.0738
116 Y B 0.0000
117 S B -0.0540
118 T B 0.0000
119 T B -0.0322
120 A B 0.0000
121 V B 1.4301
122 V B 0.5194
123 T B -0.2162
124 N B -1.2857
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Automated mutations analysis

In the automated mutations mode, the server selects aggregation prone resides and each selected residue is mutated to glutamic acid, lysine, aspartic acid and arginine. The table below shows 2 best scored mutants for each mutated residue. Protein variants are ordered according to the mutation effect they had on protein stability (energetic effect) together with the difference in the average per-residue aggregation score between the wild type and the mutant (in the table green values indicate a positive change, grey are neutral, and orange/red mean destabilizing or more aggregation prone mutants).
Summary for all the mutants can be found in this CSV file.

Mutant
Energetic effect
Score comparison
VD65B -1.2045 -0.0155 View CSV PDB
VR65B -0.8016 -0.0166 View CSV PDB
VK20B -0.7067 -0.0159 View CSV PDB
VR121A -0.6849 -0.0156 View CSV PDB
VK20A -0.6558 -0.0157 View CSV PDB
VR20A -0.4329 -0.016 View CSV PDB
VR20B -0.2639 -0.0173 View CSV PDB
VR121B -0.3898 -0.0136 View CSV PDB
VK121A -0.3448 -0.0129 View CSV PDB
VK121B -0.2889 -0.0095 View CSV PDB
VE122A -0.374 -0.0049 View CSV PDB
VK122A 0.806 -0.0053 View CSV PDB
 
Laboratory of Theory of Biopolymers 2018