structure was pairwise aligned with PDB entries 2X8BA and 4EY4 by using FATCAT server. FDA approved drugs for AD , their derivatives and heterodimers, food, Generally Recognized As Safe and medicinal grade phytochemicals with anti-AChE activity according to Dr. Duke’s phytochemical and ethnobotanical databases were retrieved from three different databases. The modeled hAChE was docked with 329 hits. PatchDock server was used as molecular-docking tool in order to determine order BI-78D3 enzyme -inhibitor AM-2282 binding affinities. The server was operated at Clustering RMSD value 4.0 and enzyme-inhibitor complex type. Results were evaluated by using top five poses for each hits on the basis of score, approximate interface area of the complex, atomic contact energy and 3D transformation values. Fifteen new heterodimers were designed on the basis of molecular structure analysis of leads. The lead phytochemicals berberastine and berberine were joined with tacrine and pyrimidine with a C-linker by using ChemDraw Ultra 8.0. Docking studies were performed and their druglikeliness was determined by methods described above. The Phyre2 is one of most popular methods for protein structure prediction. The server found maximum similarity of the target sequence provided with fold library id: d2ha2a1. It used X-ray crystal structure d2ha2a1 as template and modeled the target. A total of 536 residues out of 583 residues were modeled with 100 confidence. The software classified the enzyme as superfamily alpha/beta-hydrolases and family as acetylcholinesterase-like enzyme. The modeled hAChE structure alignment with PDB entries 2X8BA and 4EY4 by using FATCAT algorithm, showed 99.3 and 99 similarity with RMSD 0.32 and 0.65 respectively. The high percentage similarity indicates that the modeled hAChE is a better target for molecular docking as compared to torpedo enzyme. Images of modeled hAChE indicating the active site is shown in Fig 2A and 2B. Five commonly used FDA approved drugs for AD were selected and docked with the hAChE. These all turn down the breakdown of acetylcholine in the brain. This lead to increased levels of acetyl-choline in the brain, and may preserve brain function. The dockin
