title: From in silico target prediction to multi-target drug design: current databases, methods and applications.
abstract: Given the tremendous growth of bioactivity databases, the use of computational tools to predict protein targets of small molecules has been gaining importance in recent years. Applications span a wide range, from the 'designed polypharmacology' of compounds to mode-of-action analysis. In this review, we firstly survey databases that can be used for ligand-based target prediction and which have grown tremendously in size in the past. We furthermore outline methods for target prediction that exist, both based on the knowledge of bioactivities from the ligand side and methods that can be applied in situations when a protein structure is known. Applications of successful in silico target identification attempts are discussed in detail, which were based partly or in whole on computational target predictions in the first instance. This includes the authors' own experience using target prediction tools, in this case considering phenotypic antibacterial screens and the analysis of high-throughput screening data. Finally, we will conclude with the prospective application of databases to not only predict, retrospectively, the protein targets of a small molecule, but also how to design ligands with desired polypharmacology in a prospective manner.
authors.affiliation: Unilever Centre for Molecular Sciences Informatics, Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, United Kingdom.
authors.forename: Alexios
authors.initials: A
authors.lastname: Koutsoukas
authors.forename: Benjamin
authors.initials: B
authors.lastname: Simms
authors.forename: Johannes
authors.initials: J
authors.lastname: Kirchmair
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Bond
authors.forename: Alan V
authors.initials: AV
authors.lastname: Whitmore
authors.forename: Steven
authors.initials: S
authors.lastname: Zimmer
authors.forename: Malcolm P
authors.initials: MP
authors.lastname: Young
authors.forename: Jeremy L
authors.initials: JL
authors.lastname: Jenkins
authors.forename: Meir
authors.initials: M
authors.lastname: Glick
authors.forename: Robert C
authors.initials: RC
authors.lastname: Glen
authors.forename: Andreas
authors.initials: A
authors.lastname: Bender
mesh_terms: D000818:Animals; D003198:Computer Simulation; D016208:Databases, Factual; D015195:Drug Design; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D006801:Humans