For the training set, in order to reduce artificial enrichment [34] , a subset of WDI (World Drug Index) was specifically designated as inactive molecules. Firstly, WDI was filtered to eliminate compounds whose molecular weight was either less than 200 or greater than 800. In addition, the compounds whose log P is larger than 7 and the number of rotatable bonds is more than 15 should be abandoned. Secondly, the remaining 37,843 WDI compounds were subjected to diverse selection based on 2D UNITY fingerprints. The dissimilarity selection was performed by the Selector module in SYBYL, which resulted in 9950 compounds with a maximum Tanimoto index of 0.69. The active set was compiled from a diverse selection of 50 BACE-1 inhibitors from the total compounds available in the Prous Integrity Drugs & Biologics database [50] . This library of 10,000 compounds as a training set has an active content of 0.5%, which mimics real-life screening situations.