第31卷第3期厦门理工学院学报JournalofXiamenUniversityofTechnologyVol.31No.32023年6月Jun.2023GIRK2通道外流门控机制的分子动力学模拟王瑞，赵伊婷，石定媛，李岱霖*，林嫣（厦门理工学院环境科学与工程学院，福建厦门361024）［摘要］为深入理解外流调控型病理或药效机制，采用全原子分子动力学模拟方法，在外向电场作用下，对不同因子（Na+、Gβγ、Na+-Gβγ）调控下的GIRK2通道进行微秒级分子动力学模拟，揭示GIRK2通道的外向电流门控机制。结果表明：Na+和Gβγ亚基协同作用激活GIRK2通道，Na+使得GIRK2通道G-loop门控打开概率高达94.6%，显示出G-loop门控的调节作用；Gβγ主要影响HBC门控，使其打开概率为73.6%。CTD结构域内向摆动约148.8°和TM2-CTD逆向旋转约11.9°可导致G-loop门激活，而CTD外向摆动和TM2外向倾斜约38.3°导致HBC门激活。［关键词］GIRK2通道；外流门控机制；分子动力学［中图分类号］X172；Q615［文献标志码］A［文章编号］1673-4432（2023）03-0088-08AMolecularDynamicsSimulationforOutwardCurrent-GatedMechanismofGIRK2ChannelWANGRui,ZHAOYiting,SHIDingyuan,LIDailin*,LINYan(SchoolofEnvironmentalScience&Engineering,XiamenUniversityofTechnology,Xiamen361024,China)Abstract:Anall-atommoleculardynamicssimulationwasusedtosimulatethemoleculardynamicsofGIRK2channelundertheregulationofdifferentfactors(Na+,Gβγ,Na+-Gβγ)undertheactionofexternalelectricfield,bywhichtheoutwardcurrent-gatedmechanismofGIRK2channelwasrevealedandthemechanismofpathologicalregulationanddrugregulationmediatedbyGIRK2channelsbetterunderstood.TheresultsshowthatNa+andGβγreceptorsubunitssynergisticallyactivatedGIRK2channel,inwhichtheNa+makesGIRK2channelG-loopgatingopenprobabilityashighas94.6%,showingtheregulatoryeffectofG-loopgating,andGβγmainlyregulatesHBCgatingtomake73.6%ofitsopenprobability.TheactivationofG-loopgatingisduetotheinwardswingoftheCTDdomainatabout148.8°andthereverserotationofTM2-CTDatabout11.9°,whiletheextrovertedswingofCTDandtheoutwardtiltofTM2atabout38.3°leadstoHBCgateactivation.Keywords:GIRK2channel;outwardcurrent-gatedmechanism;moleculardynamicsG蛋白门控内向整流钾离子（GProtein-GatedInwardlyRectifyingK+，GIRK）通道通过...
