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Probing the inhibition of MAO-B by chalcones: an integrated approach combining molecular docking, ADME analysis, MD simulation, and MM-PBSA calculations

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Abstract

Context

Monoamine oxidase B (MAO-B), an enzyme of significant relevance in the realm of neurodegenerative disorders, has garnered considerable attention as a potential target for therapeutic intervention. Natural compounds known as chalcones have shown potential as MAO-B inhibitors. In this particular study, we employed a multimodal computational method to evaluate the inhibitory effects of chalcones on MAO-B.

Methods

Molecular docking methods were used to study and assess the complicated binding interactions that occur between chalcones and MAO-B. This extensive analysis provided a valuable and deep understanding of possible binding methods as well as the key residues implicated in the inhibition process. Furthermore, the ADME investigation gave valuable insights into the pharmacokinetic properties of chalcones. This allowed them to be assessed in terms of drug-like attributes. The use of MD simulations has benefited in the research of ligand–protein interactions’ dynamic behaviour and temporal stability. MM-PBSA calculations were also done to estimate the binding free energies and acquire a better knowledge and understanding of the binding affinity between chalcones and MAO-B. Our thorough method gives a thorough knowledge of chalcones’ potential as MAO-B inhibitors, which will be useful for future experimental validation and drug development efforts in the context of neurodegenerative illnesses.

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Data will be made available on request.

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Acknowledgements

The authors are thankful to the Researchers Supporting Project Number (RSP2024R379), King Saud University, Riyadh, Saudi Arabia, for supporting this study.

Funding

The research was funded through the Researchers Supporting Project Number (RSP2024R379), King Saud University, Riyadh, Saudi Arabia.

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Authors and Affiliations

  1. Department of Chemistry, St. Thomas College, Palai, Arunapuram P.O., Kottayam, Kerala, 686574, India

    Jisna Jose, Jibin K. Varughese & Thomas V. Mathew

  2. Department of Pharmacognosy, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia

    Mohammad Khalid Parvez

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Contributions

TVM and JKV planned the manuscript. JJ wrote the manuscript. JJ, JKV, and TVM prepared the figures, and TVM checked the manuscript and provided overall feedback. MKP was responsible for conceptualisation and project administration. All the authors reviewed the manuscript.

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Correspondence to Thomas V. Mathew.

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Jose, J., Varughese, J.K., Parvez, M.K. et al. Probing the inhibition of MAO-B by chalcones: an integrated approach combining molecular docking, ADME analysis, MD simulation, and MM-PBSA calculations. J Mol Model 30, 103 (2024). https://doi.org/10.1007/s00894-024-05889-1

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