title: Measuring molecular similarity and diversity: total pharmacophore diversity.
abstract: A novel method, total pharmacophore diversity (ToPD), based on known pharmacophore features for numerically defining molecular similarity or diversity is described. The method captures the 3D shape and functionality of molecules by the analysis of relevant intramolecular distances to generate a short and descriptive pharmacophoric fingerprint for each molecule. The ToPD fingerprints can then be used in diversity analysis, clustering, or database searching. Conformational sampling is carried out when needed by the means of molecular dynamics. Our results show that ToPD outperforms a traditional 2D fingerprint technique in all test cases.
authors.affiliation: NeoGenesis Drug Discovery Inc., 840 Memorial Drive, Cambridge, MA 02139, USA. gregm@neogenesis.com
authors.forename: G M
authors.initials: GM
authors.lastname: Makara
mesh_terms: D001555:Benzene Derivatives / Q000737:chemistry*; D051546:Cyclooxygenase 2; D015195:Drug Design; D006571:Heterocyclic Compounds / Q000737:chemistry*; D007527:Isoenzymes / Q000737:chemistry; D007536:Isomerism; D008024:Ligands; D008958:Models, Molecular; D008968:Molecular Conformation; D015394:Molecular Structure; D011451:Prostaglandin-Endoperoxide Synthases / Q000737:chemistry
chemical_list: D001555:Benzene Derivatives; D006571:Heterocyclic Compounds; D007527:Isoenzymes; D008024:Ligands; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases