A review of three‐dimensional chemical structure retrieval systems

Abstract This paper presents a review of the rapid developments that have taken place over the last few years for the searching of databases of three‐dimensional (3D) molecules. The geometric arrangement of the atoms in a 3D molecule is described by an interatomic distance matrix. This is a form of labelled graph that can thus be searched using the subgraph‐isomorphism algorithms that are widely used for searching databases of two‐dimensional (2D) molecules. Several in‐house and commercial systems have been developed for 3D database searching that are based on such techniques. These systems are reviewed and their effectiveness demonstrated by examples of their use in the discovery of novel, biologically active molecules. Current systems represent a molecule by one or a small number of low‐energy conformations and there is hence much interest in the development of representational techniques and searching algorithms that account for the full set of geometric arrangements that can be adopted by a flexible molecule.