Identification and Evaluation of Traditional Chinese Medicine Natural Compounds as Potential Myostatin Inhibitors: An In Silico Approach
Abstract
:1. Introduction
2. Method and Materials
2.1. Preparation of Target Protein and Natural Compounds Library
2.2. Evaluation of Potential Leads and Drug-Ability
2.3. Visualization and Assessment of MSTN Protein
2.4. Molecular Dynamics (MD) Simulations
3. Result and Discussion
3.1. Active Pocket Analysis
3.2. Molecular Docking, Hit Selection, and Drug-Ability Assessment
3.3. Interaction Analysis of MSTN Complexes
3.4. Molecular Dynamics Trajectory Analysis of MSTN-Ligand Complexes
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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S. No | Molecule Name | rBonds | MW (D) | LogP | LogS | H-Acceptors | H-Donors | Druglikeness | DrugScore |
---|---|---|---|---|---|---|---|---|---|
1. | ZINC85542646 | 6 | 743.105 | 9.8211 | −11.256 | 4 | 4 | 2.1393 | 0.0482794 |
2. | ZINC85569060 | 14 | 742.93 | 7.2932 | −9.232 | 8 | 7 | 1.1649 | 0.02769731 |
3. | ZINC85542795 | 8 | 735.126 | 9.3453 | −9.439 | 4 | 4 | 3.5148 | 0.1333178 |
4. | ZINC85625736 | 13 | 732.871 | 8.4908 | −9.179 | 10 | 6 | −3.2413 | 0.025806 |
5. | ZINC85542639 | 6 | 715.051 | 9.1759 | −10.588 | 4 | 4 | 2.7851 | 0.05082912 |
6. | ZINC85542627 | 6 | 717.067 | 9.5135 | −10.833 | 4 | 4 | 2.1393 | 0.04927217 |
7. | ZINC85531289 | 6 | 720.856 | 8.5678 | −8.717 | 9 | 1 | −5.2949 | 0.02028264 |
8. | ZINC85542877 | 10 | 723.115 | 9.6422 | −9.433 | 4 | 4 | 1.6451 | 0.1248953 |
9. | ZINC85542671 | 6 | 720.071 | 7.3836 | −8.911 | 5 | 5 | 4.507 | 0.1466092 |
10. | ZINC85569094 | 14 | 720.924 | 7.7686 | −8.987 | 8 | 7 | −0.80112 | 0.03387373 |
11. | ZINC85532197 | 3 | 743.063 | 8.2324 | −9.457 | 6 | 2 | 1.6002 | 0.1263831 |
12. | ZINC85532197_01 | 3 | 742.055 | 8.2324 | −9.457 | 6 | 1 | 1.6002 | 0.1264543 |
13. | ZINC85511481 | 14 | 710.817 | 6.4144 | −8.805 | 10 | 6 | −3.0206 | 0.05147698 |
14. | ZINC85569082 | 14 | 692.87 | 7.0778 | −8.648 | 8 | 7 | −0.63016 | 0.03765389 |
15. | ZINC85542801 | 6 | 699.093 | 8.6257 | −9.107 | 4 | 4 | 1.8161 | 0.1313846 |
16. | ZINC85542734 | 7 | 693.045 | 8.4862 | −9.062 | 4 | 4 | 2.1393 | 0.1351283 |
17. | ZINC85596043 | 8 | 686.87 | 8.4597 | −9.448 | 8 | 4 | −5.2779 | 0.0430603 |
18. | ZINC85531399 | 6 | 678.819 | 8.8366 | −7.533 | 8 | 1 | −4.778 | 0.02747577 |
19. | ZINC85542810 | 6 | 685.066 | 8.2215 | −8.82 | 4 | 4 | 1.5833 | 0.1331636 |
20. | ZINC85592913 | 2 | 678.819 | 7.9773 | −8.865 | 8 | 4 | −4.767 | 0.07450064 |
21. | ZINC85531346 | 3 | 676.803 | 7.8245 | −7.602 | 8 | 1 | −7.5213 | 0.02813334 |
22. | ZINC85542876 | 6 | 673.055 | 8.3219 | −8.832 | 4 | 4 | 1.8161 | 0.1365408 |
23. | ZINC95911591 | 1 | 656.816 | 9.9572 | −11.412 | 6 | 1 | −3.9286 | 0.0727493 |
24. | ZINC85542793 | 6 | 671.039 | 8.0144 | −8.677 | 4 | 4 | 1.5283 | 0.1360255 |
25. | ZINC85542803 | 6 | 671.039 | 7.9522 | −8.66 | 4 | 4 | 1.3666 | 0.134584 |
26. | ZINC85592908 | 12 | 664.792 | 7.6353 | −8.595 | 8 | 4 | −2.4411 | 0.08293768 |
27. | ZINC85531409 | 5 | 650.765 | 7.8019 | −6.708 | 8 | 1 | −5.4649 | 0.03143037 |
28. | ZINC85530919 | 7 | 644.718 | 8.5529 | −7.639 | 8 | 4 | −1.1148 | 0.0982419 |
29. | ZINC85542903 | 6 | 645.001 | 7.7106 | −8.402 | 4 | 4 | 1.5283 | 0.1435007 |
30. | ZINC85542935 | 6 | 645.001 | 7.6484 | −8.385 | 4 | 4 | 1.3666 | 0.1421086 |
31. | ZINC85542917 | 6 | 645.001 | 7.6484 | −8.385 | 4 | 4 | 1.5283 | 0.14408 |
32. | ZINC85592903 | 10 | 636.739 | 7.0594 | −7.91 | 8 | 4 | −5.2216 | 0.08549763 |
33. | ZINC85542926 | 5 | 616.947 | 7.2631 | −7.795 | 4 | 4 | 3.5148 | 0.1706919 |
34. | ZINC85531359 | 7 | 620.693 | 5.5821 | −5.48 | 10 | 2 | −9.9673 | 0.04023146 |
35. | ZINC85543487 | 1 | 629.007 | 9.673 | −9.675 | 2 | 2 | −0.43731 | 0.1041854 |
36. | ZINC85949541 | 2 | 592.69 | 6.3122 | −6.34 | 8 | 0 | 1.9873 | 0.1715774 |
37. | ZINC70454202_01 | 4 | 593.742 | 6.3699 | −6.12 | 7 | 3 | 4.6261 | 0.2320921 |
38. | ZINC70454202 | 4 | 594.749 | 6.3699 | −6.12 | 7 | 4 | 4.6261 | 0.2316766 |
39. | ZINC85543478 | 1 | 616.996 | 9.3076 | −9.498 | 2 | 2 | −0.52971 | 0.1050597 |
40. | ZINC85541065 | 3 | 576.691 | 7.2035 | −8.002 | 7 | 1 | 4.6261 | 0.147236 |
41. | ZINC85531053 | 3 | 576.647 | 6.7914 | −10.044 | 8 | 1 | 1.741 | 0.1367792 |
42. | ZINC42802834 | 2 | 562.664 | 7.0099 | −8.195 | 7 | 1 | 4.6261 | 0.1527083 |
43. | ZINC85541288 | 2 | 562.664 | 7.0327 | −8.871 | 7 | 1 | 4.8552 | 0.1497575 |
44. | ZINC95910145 | 2 | 548.637 | 6.757 | −8.557 | 7 | 2 | 4.8369 | 0.1594868 |
45. | ZINC44086846 | 2 | 546.621 | 6.8386 | −9.35 | 7 | 1 | 4.9691 | 0.1565135 |
46. | ZINC85991498_01 | 1 | 548.593 | 5.5895 | −6.867 | 8 | 2 | −1.7726 | 0.1196459 |
47. | ZINC85991498 | 2 | 548.593 | 5.5895 | −6.867 | 8 | 2 | −1.7726 | 0.1196459 |
48. | ZINC03780340 | 6 | 504.449 | 5.9594 | −10.586 | 8 | 6 | −1.1275 | 0.07115073 |
49. | ZINC14680812 | 6 | 512.513 | 2.823 | −5.007 | 8 | 7 | 0.51052 | 0.2703446 |
50. | ZINC85596478 | 3 | 482.618 | 7.2172 | −7.679 | 4 | 1 | −6.4955 | 0.04087312 |
51. | ZINC85947357_01 | 3 | 525.814 | 8.162 | −9.5 | 4 | 4 | −2.6575 | 0.04786098 |
52. | ZINC04098631 | 3 | 440.494 | 6.1569 | −7.512 | 5 | 3 | −3.1957 | 0.1446293 |
53. | Curcumin | 8 | 368.384 | 2.039 | −3.622 | 6 | 2 | −4.7745 | 0.391063 |
S. No. | Molecule | BBB Permeant | PAINS | WLOGP | TPSA | Log S | Skin Permeability | CYP2D6 Inhibitor | Carcinogenicity |
---|---|---|---|---|---|---|---|---|---|
1. | ZINC85542795 | No | 0 | 8.79 | 72.72 | −12.48 | −2.98 | No | None |
2. | ZINC85531289 | No | 0 | 7.4 | 121.5 | −10.37 | −5.04 | No | None |
3. | ZINC85542877 | No | 0 | 8.63 | 72.72 | −12.42 | −2.95 | No | None |
4. | ZINC85542671 | No | 0 | 7.73 | 84.75 | −10.87 | −4.17 | No | None |
5. | ZINC85541288 | No | 0 | 5.5 | 61.42 | −6.92 | −5.57 | No | None |
6. | ZINC85532197 | No | 0 | 8.31 | 127.62 | −10.4 | −5.24 | No | None |
7. | ZINC85511481 | No | 0 | 5.91 | 173.98 | −9.86 | −6.08 | No | None |
8. | ZINC85592908 | No | 0 | 7.13 | 117.84 | −9.54 | −5.21 | No | None |
9. | ZINC14680812 | No | 0 | 3.69 | 158.68 | −4.19 | −8.53 | No | None |
10. | ZINC85592903 | No | 0 | 6.14 | 117.84 | −8.63 | −5.67 | No | None |
11. | ZINC85531359 | No | 0 | 4.29 | 141.73 | −6.83 | −7.14 | No | None |
12. | ZINC70454202 | No | 0 | 4.59 | 92.21 | −8.13 | −5.38 | No | None |
13. | ZINC95910145 | No | 0 | 5.2 | 72.42 | −6.82 | −5.71 | No | None |
14. | ZINC44086846 | No | 0 | 5.68 | 72.75 | −6.74 | −5.76 | No | None |
15. | ZINC04098631 | No | 0 | 6.27 | 79.15 | −7.88 | −4.43 | No | None |
16. | ZINC85991498 | No | 0 | 5.39 | 109.94 | −6.7 | −6.34 | No | None |
17. | Curcumin | No | 0 | 3.15 | 93.06 | −4.83 | −6.28 | No | None |
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Ali, S.; Ahmad, K.; Shaikh, S.; Lim, J.H.; Chun, H.J.; Ahmad, S.S.; Lee, E.J.; Choi, I. Identification and Evaluation of Traditional Chinese Medicine Natural Compounds as Potential Myostatin Inhibitors: An In Silico Approach. Molecules 2022, 27, 4303. https://doi.org/10.3390/molecules27134303
Ali S, Ahmad K, Shaikh S, Lim JH, Chun HJ, Ahmad SS, Lee EJ, Choi I. Identification and Evaluation of Traditional Chinese Medicine Natural Compounds as Potential Myostatin Inhibitors: An In Silico Approach. Molecules. 2022; 27(13):4303. https://doi.org/10.3390/molecules27134303
Chicago/Turabian StyleAli, Shahid, Khurshid Ahmad, Sibhghatulla Shaikh, Jeong Ho Lim, Hee ** Chun, Syed Sayeed Ahmad, Eun Ju Lee, and Inho Choi. 2022. "Identification and Evaluation of Traditional Chinese Medicine Natural Compounds as Potential Myostatin Inhibitors: An In Silico Approach" Molecules 27, no. 13: 4303. https://doi.org/10.3390/molecules27134303