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arXiv · 2002.08983

Recent progress in molecular simulation methods for drug binding kinetics

Ariane Nunes-Alves·Daria B. Kokh·Rebecca C. Wade
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Abstract

Due to the contribution of drug-target binding kinetics to drug efficacy, there is a high level of interest in developing methods to predict drug-target binding kinetic parameters. During the review period, a wide range of enhanced sampling molecular dynamics simulation-based methods has been developed for computing drug-target binding kinetics and studying binding and unbinding mechanisms. Here, we assess the performance of these methods considering two benchmark systems in detail: mutant T4 lysozyme-ligand complexes and a large set of N-HSP90-inhibitor complexes. The results indicate that some of the simulation methods can already be usefully applied in drug discovery or lead optimization programs but that further studies on more high-quality experimental benchmark datasets are necessary to improve and validate computational methods.

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Ariane Nunes-Alves, Daria B. Kokh, Rebecca C. Wade. 2020-02-20. Recent progress in molecular simulation methods for drug binding kinetics. https://doi.org/10.1016/j.sbi.2020.06.022

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