Computational methods for calculation of protein-ligand binding affinities in structure-based drug design

Abstract

Abstract Drug design is an expensive and time-consuming process. Any method that allows reducing the time the costs of the drug development project can have great practical value for the pharmaceutical industry. In structure-based drug design, affinity prediction methods are of great importance. The majority of methods used to predict binding free energy in protein-ligand complexes use molecular mechanics methods. However, many limitations of these methods in describing interactions exist. An attempt to go beyond these limits is the application of quantum-mechanical description for all or only part of the analyzed system. However, the extensive use of quantum mechanical (QM) approaches in drug discovery is still a demanding challenge. This chapter briefly reviews selected methods used to calculate protein-ligand binding affinity applied in virtual screening (VS), rescoring of docked poses, and lead optimization stage, including QM methods based on molecular simulations.