[Article]www.whxb.pku.edu.cn物理化学学报(WuliHuaxueXuebao)ActaPhys.-Chim.Sin.2014,30(1),183-193JanuaryReceived:August2,2013;Revised:November28,2013;PublishedonWeb:November28,2013.∗Correspondingauthor.Email:sichuan@ynu.edu.cn;Tel:+86-571-65039937.TheprojectwassupportedbytheNationalNaturalScienceFoundationofChina(21163024).国家自然科学基金(21163024)资助项目©EditorialofficeofActaPhysico-ChimicaSinicadoi:10.3866/PKU.WHXB201311281多巴胺在POPC磷脂双层膜中扩散和透过过程的分子动力学模拟张继伟1卞富永1,2施国军1徐四川1,*(1云南大学化学科学与工程学院,自然资源药物化学教育部重点实验室,昆明650091;2楚雄医药高等专科学校,云南楚雄675005)摘要:多巴胺作为脑组织内一种重要的神经递质在细胞膜内外需要做合适的迁移,发挥其功能.多巴胺在细胞膜中扩散和透过过程的分子动力学涉及到多巴胺分子保护通道的畅通,与精神分裂症等病症有关.本文采用1-棕榈酰-2-油酰-卵磷脂(POPC)双层膜模拟细胞膜,通过分子动力学模拟获得多巴胺分子在细胞膜中和透过细胞膜运动自由能变化,探讨多巴胺在细胞膜中扩散和透过过程的分子动力学.多巴胺分子在POPC磷脂双层膜中间层做扩散运动的自由能变化为10-54kJ∙mol-1(310K),显示多巴胺分子在细胞膜中间层很容易横向和纵向扩散,保持多巴胺保护通道的畅通.多巴胺分子不容易透过POPC磷脂双层膜,因为透过过程自由能能垒为117-125kJ∙mol-1(310K).因此,人脑组织神经细胞里生产的多巴胺分子可以储藏在生物细胞膜空间.而过量的多巴胺则可以通过保护通道进入磷脂双层膜结构中间,做横向和纵向扩散运动,并且透过细胞膜,避免精神分裂症的发生.生物细胞膜的正常功能对于保持多巴胺保护通道的畅通和避免精神分裂症的出现都是重要的.研究结果与其它实验观察和结果相一致.关键词:多巴胺;POPC;细胞膜;分子动力学模拟;自由能中图分类号:O641MolecularDynamicsSimulationofDopamineDiffusionwithinandPermeationthroughPOPCPhospholipidBilayerMembraneZHANGJi-Wei1BIANFu-Yong1,2SHIGuo-Jun1XUSi-Chuan1,*(1KeyLaboratoryofEducationMinistryforMedicinalChemistryofNaturalResource,CollegeofChemicalScienceandTechnology,YunnanUniversity,Kunming650091,P.R.China;2ChuxiongMedicalCollege,Chuxiong675005,YunnanProvince,P.R.China)Abstract:Dopamine,whichisanimportantneuraltransmitterinbraintissue,needstomovefreelywithinandthroughcellmembranestofulfillitsfunction.Themoleculardynamicsofdopaminediffusionwithinandpermeationthrough,cellmembranesareinvolvedinsmoothingdopaminemolecularprotectivechannels,associatedwithschizophreniaandParkinson′sdisease.Inthepresentwork,usinga1-palmitoyl-2-oleoyl-glycero-3-phosphatedylcholine(POPC)phospholipidbilayermembranetomodelthecellmembrane,weobtainedthefree-energychanges(ΔG)fordopaminediffusionwithinandpermeationthroughthecellmembrane,usingmoleculardynamicssimulations,andprobedthemoleculardynamicsofdopaminediffusionandpermeation.TheobtainedvaluesofΔGfordopaminediffusionwithinthecellmembranewere10-54kJ∙mol-1at310K,whichimpliesthatdopaminediffuseseasilyhorizontallyandverticallywithinthecellmembranetoprotectsmoothingoftheprotectivechannel.However,itisnoteasyfordopaminetopermeatethroughthecellmembrane,becauseΔGforthisprocesswas117-125kJ∙mol-1(310K).Superfluousdopaminepassesthroughthedopaminemolecularprotectivechannelandentersthemiddleregionofthephospholipidbilayermembrane,andthendiffuseseasilyalongthehorizontalandverticalorientationswithinthecellmembrane,evenpermeatingthroughthecellmembrane,preventing183ActaPhys.-Chim.Sin.2014Vol.30schizophrenia.Itisthereforeimportantforthenormalfunctionofabiologicalcellmembranetoprotectsmoothingofdopaminemolecularprotectivechannels,preve...
