This work was performed as part of a project aimed at identifying strong, selective inhibitors of b-secretase (BACE-1) to overcome the shortcomings of the existing drugs to treat Alzheimer's disease (AD) [38, 39, 40] . It is generally accepted that Alzheimer's disease is caused by extracellular senile plaque deposition and that the intracellular formation of neurofibrillary tangles in the brain. b-amyloid peptides, which form the senile plaques, are formed by the action of the b-secretase and csecretase enzyme on the amyloid precursor protein (APP) [41, 42, 43] . The design of a lead compound that can inhibit APP binding to the active site of BACE-1 will prevent the cleavage of APP from the b-amyloid peptide and thus eventually prevent senile plaque formation [44, 45] . In the present study, the training set is composed of 50 confirmed BACE-1 inhibitors and 9950 inactive compounds [46, 47, 48] . Three rank-based virtual screening methods, individual scoring, conventional consensus scoring and PCA scoring were examined to identify BACE-1 inhibitors. To validate the efficacy of PCA ranking method, after virtual screening of 113,228 compounds (Sigma-AldrichH corporate chemical directory) [49] and the BACE-1 fluorescence resonance energy transfer (FRET) assay, we found two drug-like and lowmicromolar inhibitors.