title: Homology Model and Docking-Based Virtual Screening for Ligands of the σ1 Receptor.
abstract: This study presents for the first time the 3D model of the σ1 receptor protein as obtained from homology modeling techniques, shows the applicability of this structure to docking-based virtual screening, defines a computational strategy to optimize the results based on a combination of 3D pharmacophore-based docking and MM/PBSA free energy of binding scoring, and provides evidence that these in silico models and recipes are powerful tools on which virtual screening of new σ1 ligands can be based. In particular, the validation of the applicability of docking-based virtual screening to homology models is of utmost importance, since no crystal structure is available to date for the σ1 receptor, and this missing information still constitutes a major hurdle for a rational ligand design for this important protein target.
authors.affiliation: Molecular Simulation Engineering (MOSE) Laboratory, Department of Industrial Engineering and Information Technology (DI3), University of Trieste , Via Valerio 10, 34127 Trieste, Italy.
authors.forename: Erik
authors.initials: E
authors.lastname: Laurini
authors.affiliation: Molecular Simulation Engineering (MOSE) Laboratory, Department of Industrial Engineering and Information Technology (DI3), University of Trieste , Via Valerio 10, 34127 Trieste, Italy.
authors.forename: Valentina Dal
authors.initials: VD
authors.lastname: Col
authors.affiliation: Department of Pharmaceutical Sciences, University of Trieste , Piazzale Europa 1, 34127 Trieste, Italy.
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Mamolo
authors.affiliation: Department of Pharmaceutical Sciences, University of Trieste , Piazzale Europa 1, 34127 Trieste, Italy.
authors.forename: Daniele
authors.initials: D
authors.lastname: Zampieri
authors.affiliation: Molecular Simulation Engineering (MOSE) Laboratory, Department of Industrial Engineering and Information Technology (DI3), University of Trieste , Via Valerio 10, 34127 Trieste, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Posocco
authors.affiliation: Molecular Simulation Engineering (MOSE) Laboratory, Department of Industrial Engineering and Information Technology (DI3), University of Trieste , Via Valerio 10, 34127 Trieste, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Fermeglia
authors.affiliation: Department of Pharmaceutical Sciences, University of Trieste , Piazzale Europa 1, 34127 Trieste, Italy.
authors.forename: Luciano
authors.initials: L
authors.lastname: Vio
authors.affiliation: Molecular Simulation Engineering (MOSE) Laboratory, Department of Industrial Engineering and Information Technology (DI3), University of Trieste , Via Valerio 10, 34127 Trieste, Italy.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Pricl
keywords: 3D pharmacophore model; docking; free energy of binding; homology modeling; virtual screening; σ1 Receptor