title: Physics-based methods for studying protein-ligand interactions.
abstract: 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.
authors.affiliation: Department of Pharmaceutical Chemistry, University of California San Francisco, 600 16th Street, San Francisco, CA 94158-2517, USA.
authors.forename: Niu
authors.initials: N
authors.lastname: Huang
authors.forename: Matthew P
authors.initials: MP
authors.lastname: Jacobson
mesh_terms: D001665:Binding Sites; D017076:Computer-Aided Design; D015195:Drug Design; D008024:Ligands; D008956:Models, Chemical; D015394:Molecular Structure; D004364:Pharmaceutical Preparations / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism; D013329:Structure-Activity Relationship; D013678:Technology, Pharmaceutical / Q000379:methods*; D013816:Thermodynamics
chemical_list: D008024:Ligands; D004364:Pharmaceutical Preparations; D011506:Proteins