Chem.J.ChineseUniversities,2023,44(2),2022050020220500(1/10)CHEMICALJOURNALOFCHINESEUNIVERSITIES高等学校化学学报研究论文天然产物法卡林二醇与人类GABAA受体相互作用的机制沈琦1，陈海瑶1，高登辉1，赵熹1，那日松2，刘佳2，黄旭日1（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）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(GABAA)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GABAA受体作用及相应药物开发提供了理论依据.关键词法卡林二醇；γ-氨基丁酸A型受体；分子动力学模拟；拮抗作用中图分类号O641文献标志码Adoi：10.7503/cjcu20220500InteractionMechanismoftheNaturalProductFalcarindiolandHumanGABAAReceptorSHENQi1，CHENHaiyao1，GAODenghui1，ZHAOXi1*，NARisong2，LIUJia2，HUANGXuri1（1.InstituteofTheoreticalChemistry，JilinUniversity，Changchun130061，China；2.CollegeofPlantProtection，HenanAgriculturalUniversity，Zhengzhou450046，China）AbstractFalcarindiolisanaturalpolyacetylenealcoholcompoundthathasdemonstratedanti-inflammatory，neuro⁃logicalandpotentiallyanticancerproperties，andmodulatestheactivityoftheγ-aminobutyricacidtypeA（GABAA）receptorwhichisanimportanttherapeutictargetforneurologicaldisordersinhumans，butthemechanismofactionisnotclear.Inthispaper，thebindingmodeanddynamicpropertiesoffalcarindiolactingonGABAAreceptorwereinvestigatedbymoleculardynamicssimulation，umbrellasamplingsimulations，bindingfreeenergycalculationsandmoleculardocking，anddeterminedthatallthreeeffectivebindingsiteshaveantagonisticeffectsonthisreceptor.ThisworkwillprovideatheoreticalbasisforthesubsequentstudyoftheeffectsofpolyethynylalcoholanaloguesonGABAAreceptorsandthecorrespondingdrugdevelopment.KeywordsFalcarindiol；γ-AminobutyricacidtypeA（GABAA）receptor；Moleculardynamicssimulation；Antagonism神经退行性疾病是大脑和脊髓的细胞神经退行性变形、丢失而导致的疾病.如帕金森、阿尔兹海默症、癫痫和亨廷顿舞蹈症等均为神经退行性疾病，主要表现为认知功...
