Experiences with searching for molecular similarity in conformationally flexible 3D databases

A key step within a modern drug design strategy is the generation of a lead compound. This process can be greatly enhanced by the use of three–dimensional (3D) database searching, where compounds with molecular similarity or complementarity can be extracted from large databases of 3D structures. The use of 3D databases in drug design is the subject of much current interest, and several new commercial software packages for 3D database searching are now available. Recent reviews are available for this topic (Martin, 1992), and more specifically for the generation and use of 3D molecular structures in 3D searching (Pearlman, 1994); software for general molecular modelling, often needed for defining the search criteria or analysing the results, is catalogued in a recent compendium by Boyd (1994).