title: Molecular dynamics to enhance structure-based virtual screening on cathepsin B.
abstract: Molecular dynamics (MD) and molecular docking are commonly used to study molecular interactions in drug discovery. Most docking approaches consider proteins as rigid, which can decrease the accuracy of predicted docked poses. Therefore MD simulations can be used prior to docking to add flexibility to proteins. We evaluated the contribution of using MD together with docking in a docking study on human cathepsin B, a well-studied protein involved in numerous pathological processes. Using CHARMM biomolecular simulation program and AutoDock Vina molecular docking program, we found, that short MD simulations significantly improved molecular docking. Our results, expressed with the area under the receiver operating characteristic curves, show an increase in discriminatory power i.e. the ability to discriminate active from inactive compounds of molecular docking, when docking is performed to selected snapshots from MD simulations.
authors.affiliation: National Institute of Chemistry, Hajdrihova 19, 1000, Ljubljana, Slovenia.
authors.forename: Mitja
authors.initials: M
authors.lastname: Ogrizek
authors.forename: Samo
authors.initials: S
authors.lastname: Turk
authors.forename: Samo
authors.initials: S
authors.lastname: Lešnik
authors.forename: Izidor
authors.initials: I
authors.lastname: Sosič
authors.forename: Milan
authors.initials: M
authors.lastname: Hodošček
authors.forename: Bojana
authors.initials: B
authors.lastname: Mirković
authors.forename: Janko
authors.initials: J
authors.lastname: Kos
authors.forename: Dušanka
authors.initials: D
authors.lastname: Janežič
authors.forename: Stanislav
authors.initials: S
authors.lastname: Gobec
authors.forename: Janez
authors.initials: J
authors.lastname: Konc
mesh_terms: D002401:Cathepsin B / Q000737:chemistry* / Q000378:metabolism; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D006801:Humans; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D011487:Protein Conformation; D012372:ROC Curve; D054852:Small Molecule Libraries / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D054852:Small Molecule Libraries; D002401:Cathepsin B