Structural modeling of Na_(v)1.5 pore domain in closed state  

作　　者：Xiaofeng Ji Yanzhao Huang Jun Sheng 

机构地区：[1]Yellow Sea Fisheries Research Institute,Chinese Academy of Fishery Sciences,Qingdao 266071,Shandong,China [2]School of Physics,Huazhong University of Science and Technology,Wuhan 430074,China

出　　处：《Biophysics Reports》2021年第4期341-354,共14页生物物理学报（英文版）

基　　金：This work is supported by the Central Public-interest Scientific Institution Basal Research Fund,YSFRI,CAFS(20603022019023 and 20603022017006);The Independent innovation and transformation of achievements of Zaozhuang(2019GH01).

摘　　要：The voltage-dependent cardiac sodium channel plays a key role in cardiac excitability and conduction and it is the drug target of medically important.However,its atomic-resolution structure is still lack.Here,we report a modeled structure of Nav1.5 pore domain in closed state.The structure was constructed by Rosetta-membrane homology modeling method based on the template of eukaryotic Nav channel NavPaS and selected by energy and direct coupling analysis(DCA).Moreover,this structure was optimized through molecular dynamical simulation in the lipid membrane bilayer.Finally,to validate the constructed model,the binding energy and binding sites of closed-state local anesthetics(LAs)in the modeled structure were computed by the MM-GBSA method and the results are in agreement with experiments.The modeled structure of Nav1.5 pore domain in closed state may be useful to explore molecular mechanism of a state-dependent drug binding and helpful for new drug development.

关 键 词：Nav1.5 ion channel Closed state Homology modeling Direct coupling analysis Local anesthetics Drug binding 

分 类 号：Q617[生物学—生物物理学]