AUTHOR=Ahmad Katya , Rizzi Andrea , Capelli Riccardo , Mandelli Davide , Lyu Wenping , Carloni Paolo 

TITLE=Enhanced-Sampling Simulations for the Estimation of Ligand Binding Kinetics: Current Status and Perspective

JOURNAL=Frontiers in Molecular Biosciences

VOLUME=Volume 9 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/molecular-biosciences/articles/10.3389/fmolb.2022.899805

DOI=10.3389/fmolb.2022.899805

ISSN=2296-889X

ABSTRACT=<p>The dissociation rate (<italic>k</italic><sub>off</sub>) associated with ligand unbinding events from proteins is a parameter of fundamental importance in drug design. Here we review recent major advancements in molecular simulation methodologies for the prediction of <italic>k</italic><sub>off</sub>. Next, we discuss the impact of the potential energy function models on the accuracy of calculated <italic>k</italic><sub>off</sub> values. Finally, we provide a perspective from high-performance computing and machine learning which might help improve such predictions.</p>