Recent progress in molecular simulation methods for drug binding kinetics

• Verfasst von: Nunes-Alves, Ariane [VerfasserIn]
• Verfasst von: Kokh, Daria B. [VerfasserIn]
• Verfasst von: Wade, Rebecca C. [VerfasserIn]
• Titel: Recent progress in molecular simulation methods for drug binding kinetics
• Verf.angabe: Ariane Nunes-Alves, Daria B Kokh and Rebecca C Wade
• E-Jahr: 2020
• Jahr: 6 August 2020
• Umfang: 8 S.
• Fussnoten: Gesehen am 25.11.2020
• Titel Quelle: Enthalten in: Current opinion in structural biology
• Ort Quelle: Amsterdam [u.a.] : Elsevier, 1991
• Jahr Quelle: 2020
• Band/Heft Quelle: 64(2020), Seite 126-133
• DOI: doi:10.1016/j.sbi.2020.06.022
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1740983467

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.