identification of bace1 inhibitors for alzheimer's disease using molecular docking method

Alzheimer’s disease (ad), is a neurodegenerative, progressive, and fatal disorder, is the leadingcause of dementia threatening the elderly population [1]. bace1, a candidate β-secretase enzyme,initiates the pathogenesis of alzheimer s disease (ad) through the production of amyloid β peptide(aβ), which serves as a potential therapeutic target [2]. the 3d structure of bace1, with the pdbid of 4ivs and resolution of 2.64 å was retrieved from protein data bank (www.rcsb.org). thenatural isoprenylated coumarins including mesuol, and isomesuol were obtained from thepubchem server as 3d structures in sdf files. after validation, these compounds wereinvestigated by docking studies and the compounds with best docking score have been selected.the binding energy and main interactions between the mesuol and isomesuol and bace1 bindingpocket were investigated in detail. the mesuol and isomesuol had a good capability to block thebace1 with the binding affinity of -10.79 and -10.44 kcal/mol. in addition, these compoundspassed lipinski’s “rule of five”. these findings suggest that these compounds could be used forbace1 inhibition in the alzheimer’s disease, after more investigation.