Computational Analysis of Triazole-Based Kojic Acid Analogs as Tyrosinase Inhibitors by Molecular Dynamics and Free Energy Calculations
Abstract
1. Introduction
2. Results and Discussion
2.1. Molecular Docking and MD Simulations
2.2. Binding Free Energy and Per-Residual Analysis
3. Materials and Methods
3.1. System Setup for Molecular Docking and MD Simulations
3.2. Binding Free Energy Calculations: LIE Method
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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KA Analog | MOLDOCK Scoring | IC50 * |
---|---|---|
6a | −120.78 | 1.33 |
6b | −132.33 | 0.88 |
6c | −132.03 | 0.69 |
6d | −128.15 | 6.80 |
6e | −125.68 | 1.07 |
6f | −136.38 | 0.99 |
6g | −129.55 | 1.12 |
6h | −139.06 | 6.29 |
6i | −132.92 | 0.52 |
6j | −135.60 | 2.64 |
6k | −132.85 | 1.32 |
6l | −125.93 | 1.24 |
6m | −130.46 | 0.87 |
6n | −130.17 | 0.74 |
6o | −130.15 | 0.06 |
6p | −131.51 | 0.30 |
System | Protein RMSD | Ligand RMSD |
---|---|---|
TYR-6a | 0.44 ± 0.05 | 0.47 ± 0.15 |
TYR-6b | 0.50 ± 0.04 | 0.80 ± 0.20 |
TYR-6c | 0.46 ± 0.07 | 0.53 ± 0.14 |
TYR-6d | 0.40 ± 0.03 | 0.51 ± 0.16 |
TYR-6e | 0.40 ± 0.05 | 0.60 ± 0.20 |
TYR-6f | 0.44 ± 0.04 | 0.81 ± 0.24 |
TYR-6g | 0.45 ± 0.03 | 0.79 ± 0.21 |
TYR-6h | 0.43 ± 0.04 | 0.54 ± 0.13 |
TYR-6i | 0.44 ± 0.05 | 0.51 ± 0.13 |
TYR-6j | 0.43 ± 0.03 | 0.47 ± 0.12 |
TYR-6k | 0.44 ± 0.04 | 0.62 ± 0.16 |
TYR-6l | 0.43 ± 0.05 | 0.57 ± 0.13 |
TYR-6m | 0.49 ± 0.06 | 0.55 ± 0.13 |
TYR-6n | 0.47 ± 0.04 | 0.79 ± 0.19 |
TYR-6o | 0.39 ± 0.04 | 0.49 ± 0.13 |
TYR-6p | 0.46 ± 0.06 | 0.50 ± 0.13 |
KA Analog | ∆GLIE | ∆GEXP | ||||
---|---|---|---|---|---|---|
6a | −26.21 ± 0.01 | −26.70 ± 0.49 | −49.16 ± 0.98 | −84.09 ± 0.24 | −8.03 ± 0.45 | −8.07 |
6b | −26.31 ± 0.06 | −26.91 ± 0.10 | −46.90 ± 0.34 | −85.71 ± 0.63 | −8.13 ± 0.34 | −8.31 |
6c | −27.77 ± 0.02 | −25.57 ± 0.17 | −49.79 ± 0.41 | −84.45 ± 0.70 | −8.41 ± 0.40 | −8.46 |
6e | −26.24 ± 0.03 | −26.97 ± 0.31 | −46.53 ± 0.21 | −85.27 ± 0.76 | −7.89 ± 0.44 | −8.20 |
6f | −27.61 ± 0.02 | −25.32 ± 0.18 | −50.79 ± 0.90 | −82.86 ± 0.89 | −8.13 ± 0.56 | −8.24 |
6h | −28.48 ± 0.08 | −30.39 ± 0.45 | −51.28 ± 0.29 | −89.28 ± 0.78 | −6.20 ± 0.47 | −7.14 |
6i | −29.42 ± 0.04 | −29.93 ± 0.02 | −55.29 ± 0.51 | −89.10 ± 0.26 | −9.21 ± 0.20 | −8.63 |
6j | −30.14 ± 0.08 | −42.95 ± 0.30 | −55.83 ± 0.37 | −99.47 ± 0.97 | −7.07 ± 0.53 | −7.66 |
6l | −28.59 ± 0.03 | −28.16 ± 0.16 | −50.52 ± 0.68 | −86.78 ± 1.01 | −8.30 ± 0.56 | −8.11 |
6m | −31.90 ± 0.10 | −33.77 ± 0.61 | −57.72 ± 0.40 | −90.52 ± 0.99 | −8.31 ± 0.68 | −8.32 |
6n | −28.72 ± 0.09 | −29.18 ± 0.74 | −49.41 ± 0.79 | −88.77 ± 0.90 | −8.44 ± 0.76 | −8.42 |
6o | −29.99 ± 0.30 | −27.33 ± 0.05 | −61.99 ± 0.37 | −87.15 ± 0.24 | −10.56 ± 0.23 | −9.91 |
6p | −30.01 ± 0.20 | −27.97 ± 0.43 | −61.40 ± 0.91 | −86.21 ± 0.22 | −9.80 ± 0.44 | −8.95 |
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Martins, L.S.; Gonçalves, R.W.A.; Moraes, J.J.S.; Alves, C.N.; Silva, J.R.A. Computational Analysis of Triazole-Based Kojic Acid Analogs as Tyrosinase Inhibitors by Molecular Dynamics and Free Energy Calculations. Molecules 2022, 27, 8141. https://doi.org/10.3390/molecules27238141
Martins LS, Gonçalves RWA, Moraes JJS, Alves CN, Silva JRA. Computational Analysis of Triazole-Based Kojic Acid Analogs as Tyrosinase Inhibitors by Molecular Dynamics and Free Energy Calculations. Molecules. 2022; 27(23):8141. https://doi.org/10.3390/molecules27238141
Chicago/Turabian StyleMartins, Lucas Sousa, Reinaldo W. A. Gonçalves, Joana J. S. Moraes, Cláudio Nahum Alves, and José Rogério A. Silva. 2022. "Computational Analysis of Triazole-Based Kojic Acid Analogs as Tyrosinase Inhibitors by Molecular Dynamics and Free Energy Calculations" Molecules 27, no. 23: 8141. https://doi.org/10.3390/molecules27238141
APA StyleMartins, L. S., Gonçalves, R. W. A., Moraes, J. J. S., Alves, C. N., & Silva, J. R. A. (2022). Computational Analysis of Triazole-Based Kojic Acid Analogs as Tyrosinase Inhibitors by Molecular Dynamics and Free Energy Calculations. Molecules, 27(23), 8141. https://doi.org/10.3390/molecules27238141