The accurate prediction of relative or absolute ligand-binding affinities is challenging in both theoretical and practical aspects. However, with the aid of advanced computing power and sophisticated methodology development, physics-based free-energy calculations, which can be used to predict ligand-binding affinities, have become increasingly utilized in the field of structure-based drug design. This review summarizes recent progress made in developing and applying physics-based methods to studying protein-ligand interactions, focusing on methods using molecular mechanics force fields. Applications of these methods include predicting ligand binding poses, enriching binders in virtual screening, and calculating relative and absolute binding free energies. Future directions for further improving current physics-based methods are also discussed.
Physics-based methods for studying protein-ligand interactions. Publishing Authors By Initials
