title: In silico multi-filter screening approaches for developing novel beta-secretase inhibitors.
abstract: A large database of chemical structures was screened for potential inhibitors of beta-secretase was carried out using in silico multi-filter techniques. Substructure screening, computer-aided ligand docking, binding free energy calculations, and partial interaction energy analyses were performed successively to identify chemical compounds which could serve as different scaffolds from known beta-secretase inhibitors for future drug design. We showed that our in silico multi-filter screening retrieved all known inhibitors from the compound database investigated, which suggests that the other compounds identified as inhibitors by this computerized screening process are potential beta-secretase inhibitors.
authors.affiliation: School of Pharmaceutical Sciences, Kitasato University, 5-9-1, Shirokane, Minato-ku, Tokyo, Japan.
authors.forename: Taku
authors.initials: T
authors.lastname: Fujimoto
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Matsushita
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Gouda
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Yamaotsu
authors.forename: Shuichi
authors.initials: S
authors.lastname: Hirono
mesh_terms: D000465:Algorithms; D053829:Amyloid Precursor Protein Secretases / Q000037:antagonists & inhibitors* / Q000737:chemistry; D001665:Binding Sites; D003198:Computer Simulation; D017076:Computer-Aided Design; D016208:Databases, Factual; D015195:Drug Design; D008968:Molecular Conformation; D011480:Protease Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D013816:Thermodynamics
chemical_list: D011480:Protease Inhibitors; D053829:Amyloid Precursor Protein Secretases