In recent decades,the development of high-performance computing (HPC)continues to follow Moore\'s law,with many computational methods in drug design experiencing a renaissance.Binding prediction,virtual screening,molecular dynamics simulations and protein folding are crucial applications of computational drug design to accelerate drug discovery (Fig.1).Reliable pre-diction of the receptor/ligand binding affinities that determine the pharma-cological effects of drugs is the most important application of HPC in drug discovery,and is the main focus of this Perspective.