In silico multi-filter screening approaches for developing novel β-secretase inhibitors

A large database of chemical structures was screened for potential inhibitors of β-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 β-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 β-secretase inhibitors.

Graphical abstractA large database of chemical structures was screened for potential novel inhibitors of β-secretase using in silico multi-filter techniques. Compounds with a calculated strong binding free energy to β-secretase were selected as ‘hits’. The hits included all the compounds already identified as β-secretase inhibitors in the database, which validates the effectiveness of our in silico screening methods.Figure optionsDownload full-size imageDownload as PowerPoint slide