基于分子对接的虚拟筛选研究 FDA 批准药物及其代谢产物的胆碱能选择性。

Department of Chemistry and Biochemistry, Southern Connecticut State University, New Haven, CT 06515, USA.

Department of Chemistry and Chemical & Biochemical Engineering, University of New Haven, West Haven, CT 06516, USA.

Molecules. 2024 May 16;29(10):2333. doi: 10.3390/molecules29102333.

The search for selective anticholinergic agents stems from varying cholinesterase levels as Alzheimer's Disease progresses from the mid to late stage. In this computational study, we probed the selectivity of FDA-approved and metabolite compounds against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) with molecular-docking-based virtual screening. The results were evaluated using locally developed codes for the statistical methods. The docking-predicted selectivity for AChE and BChE was predominantly the consequence of differences in the volume of the active site and the narrower entrance to the bottom of the active site gorge of AChE.

对选择性抗胆堿能药物的研究源于阿尔茨海默病从中期到晚期的不同胆堿酯酶水平。在这项计算研究中，我们通过基于分子对接的虚拟筛选，研究了 FDA 批准的化合物及其代谢物对乙酰胆堿酯酶 (AChE) 和丁酰胆堿酯酶 (BChE) 的选择性。使用本地开发的统计方法代码评估了结果。AChE 和 BChE 的对接预测选择性主要是由于 AChE 的活性位点体积差异以及活性位点底部入口较窄所致。