Identification of Human Acetylcholine Esterase Inhibitors from the Constituents of EGb761 by Modeling Docking and Molecular Dynamics Simulations.

Identification of Human Acetylcholine Esterase Inhibitors from the Constituents of EGb761 by Modeling Docking and Molecular Dynamics Simulations. Comb Chem High Throughput Screen. 2017 Nov 23;: Authors: Zhang L, Li D, Cao F, Xiao W, Zhao L, Wang Z, Ding G Abstract EGb761, a standardized and well-defined product extract of Ginkgo biloba leaves, has beneficial effects on the treatment of multiple diseases, particularly Alzheimer's disease (AD). Identification of natural acetylcholine esterase (AChE) inhibitors from EGb761 would provide a novel therapeutic approach against the Alzheimer's disease. A series of 21 kinds of promising EGB761 compounds were selected, and subsequently evaluated for their potential ability to bind AChE enzyme by molecular docking and a deep analysis of protein surface pocket features. Docking results indicated that these compounds can bind tightly with the active site of human AChE, with favorable distinct interactions around several important residues Asp74, Leu289, Phe295, Ser293, Tyr341, Trp286 and Val294 in the active pocket. Most EGB761 compounds could form the hydrogen bond interactions with the positively charged Asp74 and Phe295 residues. Among these compounds, diosmetin is the one with the best-predicted docking score while three key hydrogen bonds can be formed between small molecule and corresponding residues of the binding site. Besides, other three compounds luteolin, apigenin, and isorhamnetin ha...
Source: Combinatorial Chemistry and High Throughput Screening - Category: Chemistry Authors: Tags: Comb Chem High Throughput Screen Source Type: research