The Donepezil which is an Acetylcholinesterase inhibitor compound was downloaded from the pub med the cyclohexamine core was substituted with natural drug fragment cores generating the ligand library, and the library compound structure was optimized by DFT methods (B3LYP-D3/6-31G** Basis set). The ligands are added to the PyRx software and the target protein active site grid file was input the high throughput virtual screening helped to scan huge library compounds giving some finer compounds with all the possess of binding. The single structure having Zero rmsd is selected for the post-dock analysis.