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Computational Analysis of Triazole-Based Kojic Acid Analogs as Tyrosinase Inhibitors by Molecular Dynamics and Free Energy Calculations

Molecular docking, molecular dynamics (MD) simulations and the linear interaction energy (LIE) method were used here to predict binding modes and free energy for a set of 1,2,3-triazole-based KA analogs as potent inhibitors of Tyrosinase (TYR), a key metalloenzyme of the melanogenesis process. Initi...

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Autores principales: Martins, Lucas Sousa, Gonçalves, Reinaldo W. A., Moraes, Joana J. S., Alves, Cláudio Nahum, Silva, José Rogério A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9735930/
https://www.ncbi.nlm.nih.gov/pubmed/36500237
http://dx.doi.org/10.3390/molecules27238141
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author Martins, Lucas Sousa
Gonçalves, Reinaldo W. A.
Moraes, Joana J. S.
Alves, Cláudio Nahum
Silva, José Rogério A.
author_facet Martins, Lucas Sousa
Gonçalves, Reinaldo W. A.
Moraes, Joana J. S.
Alves, Cláudio Nahum
Silva, José Rogério A.
author_sort Martins, Lucas Sousa
collection PubMed
description Molecular docking, molecular dynamics (MD) simulations and the linear interaction energy (LIE) method were used here to predict binding modes and free energy for a set of 1,2,3-triazole-based KA analogs as potent inhibitors of Tyrosinase (TYR), a key metalloenzyme of the melanogenesis process. Initially, molecular docking calculations satisfactorily predicted the binding mode of evaluated KA analogs, where the KA part overlays the crystal conformation of the KA inhibitor into the catalytic site of TYR. The MD simulations were followed by the LIE method, which reproduced the experimental binding free energies for KA analogs with an r(2) equal to 0.97, suggesting the robustness of our theoretical model. Moreover, the van der Waals contributions performed by some residues such as Phe197, Pro201, Arg209, Met215 and Val218 are responsible for the binding recognition of 1,2,3-triazole-based KA analogs in TYR catalytic site. Finally, our calculations provide suitable validation of the combination of molecular docking, MD, and LIE approaches as a powerful tool in the structure-based drug design of new and potent TYR inhibitors.
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spelling pubmed-97359302022-12-11 Computational Analysis of Triazole-Based Kojic Acid Analogs as Tyrosinase Inhibitors by Molecular Dynamics and Free Energy Calculations Martins, Lucas Sousa Gonçalves, Reinaldo W. A. Moraes, Joana J. S. Alves, Cláudio Nahum Silva, José Rogério A. Molecules Article Molecular docking, molecular dynamics (MD) simulations and the linear interaction energy (LIE) method were used here to predict binding modes and free energy for a set of 1,2,3-triazole-based KA analogs as potent inhibitors of Tyrosinase (TYR), a key metalloenzyme of the melanogenesis process. Initially, molecular docking calculations satisfactorily predicted the binding mode of evaluated KA analogs, where the KA part overlays the crystal conformation of the KA inhibitor into the catalytic site of TYR. The MD simulations were followed by the LIE method, which reproduced the experimental binding free energies for KA analogs with an r(2) equal to 0.97, suggesting the robustness of our theoretical model. Moreover, the van der Waals contributions performed by some residues such as Phe197, Pro201, Arg209, Met215 and Val218 are responsible for the binding recognition of 1,2,3-triazole-based KA analogs in TYR catalytic site. Finally, our calculations provide suitable validation of the combination of molecular docking, MD, and LIE approaches as a powerful tool in the structure-based drug design of new and potent TYR inhibitors. MDPI 2022-11-23 /pmc/articles/PMC9735930/ /pubmed/36500237 http://dx.doi.org/10.3390/molecules27238141 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Martins, Lucas Sousa
Gonçalves, Reinaldo W. A.
Moraes, Joana J. S.
Alves, Cláudio Nahum
Silva, José Rogério A.
Computational Analysis of Triazole-Based Kojic Acid Analogs as Tyrosinase Inhibitors by Molecular Dynamics and Free Energy Calculations
title Computational Analysis of Triazole-Based Kojic Acid Analogs as Tyrosinase Inhibitors by Molecular Dynamics and Free Energy Calculations
title_full Computational Analysis of Triazole-Based Kojic Acid Analogs as Tyrosinase Inhibitors by Molecular Dynamics and Free Energy Calculations
title_fullStr Computational Analysis of Triazole-Based Kojic Acid Analogs as Tyrosinase Inhibitors by Molecular Dynamics and Free Energy Calculations
title_full_unstemmed Computational Analysis of Triazole-Based Kojic Acid Analogs as Tyrosinase Inhibitors by Molecular Dynamics and Free Energy Calculations
title_short Computational Analysis of Triazole-Based Kojic Acid Analogs as Tyrosinase Inhibitors by Molecular Dynamics and Free Energy Calculations
title_sort computational analysis of triazole-based kojic acid analogs as tyrosinase inhibitors by molecular dynamics and free energy calculations
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9735930/
https://www.ncbi.nlm.nih.gov/pubmed/36500237
http://dx.doi.org/10.3390/molecules27238141
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