Three-dimensional database searching of bioactive compounds and their application

Recent advances in computer technology and dramatic cost reductions for phy sical memory and operation speed now allow the ability to access the millio ns of compounds needed to search and analyze three-dimensional (3D) structu ral as well as conformational information. As a result, 3D database searchi ng methods are considerably useful in finding and designing novel biologica lly active compounds. In the presence of a protein structure, 3D databases are searched directly for potential compounds fitting a known receptor bind ing site. In the absence of a protein structure, 3D databases can be search ed indirectly, fitting known lead compounds on the basis of pharmacophore. As reviewed in this article, 3D database searching can provide valuable inf ormation to medicinal chemists, offering an expanding range of tools to enh ance the lead drug discovery and evolution process.