title: The effect of ligand-based tautomer and protomer prediction on structure-based virtual screening.
abstract: As tautomerism and ionization may significantly change the interaction possibilities between a ligand and a target protein, these phenomena could have an effect on structure-based virtual screening. Tautomeric- and protonation-state enumeration ensures that the state with optimal interaction possibilities is included in the screening process, as the predicted state may not always be the optimal binder. However, there is very little information published if tautomer and protomer enumeration actually improves the enrichment of active molecules compared to the alternative of using a predicted form of each molecule. In this study, a retrospective virtual screening was performed using AutoDock on 19 drug targets with a publicly available data set. It is proposed that tautomer and protomer prediction can significantly save computing resources and can yield similar results to enumeration.
authors.affiliation: Biocenter Kuopio (BCK) and Department of Pharmaceutical Chemistry, University of Kuopio, P.O. Box 1627, 70211 Kuopio, Finland. tuomo.kalliokoski@uku.fi
authors.forename: Tuomo
authors.initials: T
authors.lastname: Kalliokoski
authors.forename: Heikki S
authors.initials: HS
authors.lastname: Salo
authors.forename: Maija
authors.initials: M
authors.lastname: Lahtela-Kakkonen
authors.forename: Antti
authors.initials: A
authors.lastname: Poso
mesh_terms: D018360:Crystallography, X-Ray; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D007536:Isomerism; D008024:Ligands; D008958:Models, Molecular; D008968:Molecular Conformation; D004364:Pharmaceutical Preparations / Q000737:chemistry; D011522:Protons; D015203:Reproducibility of Results; D014584:User-Computer Interface
chemical_list: D008024:Ligands; D004364:Pharmaceutical Preparations; D011522:Protons