天然产物法卡林二醇与人类GABA_(A)受体相互作用的机制  

Interaction Mechanism of the Natural Product Falcarindiol and Human GABA A Receptor

作　　者：沈琦 陈海瑶 高登辉 赵熹[1] 那日松[2] 刘佳[2] 黄旭日[1] SHEN Qi;CHEN Haiyao;GAO Denghui;ZHAO Xi;NA Risong;LIU Jia;HUANG Xuri(Institute of Theoretical Chemistry,Jilin University,Changchun 130061,China;College of Plant Protection,Henan Agricultural University,Zhengzhou 450046,China)

机构地区：[1]吉林大学理论化学研究所,长春130061 [2]河南农业大学植物保护学院,郑州450046

出　　处：《高等学校化学学报》2023年第2期114-123,共10页Chemical Journal of Chinese Universities

基　　金：国家自然科学基金(批准号:21702048);河南农业大学教学改革项目(批准号:2021XJGLX100)资助。

摘　　要：通过分子动力学模拟、伞形采样模拟、结合自由能计算和分子对接等方法,研究了法卡林二醇在γ-氨基丁酸A型(GABA_(A))受体上结合作用的模式和对GABAA受体动态属性的影响,确定了3个有效结合位点均对此受体产生拮抗作用,为后续研究聚乙炔醇类化合物对GABA_(A)受体作用及相应药物开发提供了理论依据.Falcarindiol is a natural polyacetylene alcohol compound that has demonstrated anti-inflammatory,neuro⁃logical and potentially anticancer properties,and modulates the activity of theγ-aminobutyric acid type A(GABA_(A))receptor which is an important therapeutic target for neurological disorders in humans,but the mechanism of action is not clear.In this paper,the binding mode and dynamic properties of falcarindiol acting on GABA_(A) receptor were investigated by molecular dynamics simulation,umbrella sampling simulations,binding free energy calculations and molecular docking,and determined that all three effective binding sites have antagonistic effects on this receptor.This work will provide a theoretical basis for the subsequent study of the effects of polyethynyl alcohol analogues on GABAA receptors and the corresponding drug development.

关 键 词：法卡林二醇 γ-氨基丁酸A型受体 分子动力学模拟 拮抗作用 

分 类 号：O641[理学—物理化学]