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