title: Use of reduced graphs to encode bioisosterism for similarity-based virtual screening.
abstract: This paper describes a project to include explicit information about bioisosteric equivalences between pairs of fragment substructures in a system for similarity-based virtual screening. Data from the BIOSTER database show that reduced graphs provide a simple way of encoding known bioisosteric equivalences in a manner that can be used during similarity searching. Scaffold-hopping experiments with the WOMBAT database show that including such information enables similarities to be identified between the reference structures and active structures from the database that contain different, but equivalent, fragment substructures. However, such equivalences also contribute to the similarities between the reference structures and inactives, and the latter equivalences can swamp those involving the actives. This presents serious problems for the routine use of information about bioisosteric fragments in similarity-based virtual screening.
authors.affiliation: Krebs Institute for Biomolecular Research and Department of Information Studies, University of Sheffield, Sheffield S1 4DP, United Kingdom.
authors.forename: Kristian
authors.initials: K
authors.lastname: Birchall
authors.forename: Valerie J
authors.initials: VJ
authors.lastname: Gillet
authors.forename: Peter
authors.initials: P
authors.lastname: Willett
authors.forename: Pierre
authors.initials: P
authors.lastname: Ducrot
authors.forename: Claude
authors.initials: C
authors.lastname: Luttmann
mesh_terms: D003196:Computer Graphics; D016208:Databases, Factual; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D012015:Reference Standards; D013329:Structure-Activity Relationship; D014584:User-Computer Interface