Sàng lọc các chất có khả năng ức chế asparagin endopeptidase hướng đến điều trị bệnh Alzheimer

To search for new inhibitors of asparagine endopeptidase (AEP) with the potential to treat Alzheimer’s disease (AD), this study developed in silico models for screening AEP inhibitors. The database for screening is collected from five chemical databases including 134.876 substances. The virtual screening process is carried out in the following order: 3D-pharmacophore modelling,  docking, and molecular dynamics simulation. The study has successfully built two 3D- pharmacophore models, which include a protein-based pharmacophore and a ligand-based pharmacophore, and a molecular docking model. After being screened through 3D-pharmacophore and molecular docking models, 106 compounds were successfully docked on AEP. Analysis of the functional score on 5 hits with the best scores was showed. Among these compounds, molecular dynamics simulations were run for compounds 841 and 641 and the results showed that these compounds had good binding activity to AEP.

Keywords: 3D-Pharmacophore, docking, AEP inhibitors, virtual screening

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