In silico multi-filter screening approaches for developing novel beta-secretase inhibitors.
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.
Fujimoto
Taku
T
School of Pharmaceutical Sciences, Kitasato University, 5-9-1, Shirokane, Minato-ku, Tokyo, Japan.
Matsushita
Yasuo
Y
Gouda
Hiroaki
H
Yamaotsu
Noriyuki
N
Hirono
Shuichi
S
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
D011480:Protease Inhibitors; D053829:Amyloid Precursor Protein Secretases