Computational approaches to structure-based ligand design

Abstract The first computational structure-based drug design methods came into existence in the early 1980s and are, to an extent, still in their infancy. There have been a few successes to date. With dramatic increases in computer speed, improved accuracy in ligand scoring functions, and the advent of combinatorial chemistry, there promises to be many more. In addition, the virtual explosion in the amount of available sequence and structural information has increased the need to develop these computational techniques to exploit this vast body of information. In this review, recent advances in computational methods for database searching and docking, de novo drug design, and estimation of ligand binding affinities are discussed.