Pharmacophoric pattern matching in files of three-dimensional chemical structures: use of bounded distance matrices for the representation and searching of conformationally flexible molecules

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This paper discusses the use of bounded distance matrices for the representation of conformationally flexible threedimensional (3D) molecules. It is shown that pharmacophoric pattern searches of databases of flexible 3D molecules represented in this way can be carried out using screen and geometric searching algorithms that are analogous to those used for searching databases of rigid 3D structures. Molecules matching a query pattern after the geometric search must then undergo a final conformational search to determine whether they can, in fact, adopt a conformation that matches the query. An analysis of this three-stage searching procedure shows that searching databases of flexible 3D molecules is extremely demanding of computational resources.