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.
@article{arxiv.2002.08983,
title = {Recent progress in molecular simulation methods for drug binding kinetics},
author = {Ariane Nunes-Alves and Daria B. Kokh and Rebecca C. Wade},
journal= {arXiv preprint arXiv:2002.08983},
year = {2020}
}
Comments
Figure 3 was improved. A definition of PIB was included. Reference to WE was added (ref. 20), reference to RAMD was corrected (ref. 43)