a School of Physics and Key Laboratory of Molecular Biophysics of the Ministry of Education , Huazhong University of Science and Technology , Wuhan , Hubei 430074 , China.
b Yellow Sea Fisheries Research Institute , Chinese Academy of Fishery Sciences , Qingdao , Shandong 266071 , China.
J Biomol Struct Dyn. 2018 Jul;36(9):2268-2278. doi: 10.1080/07391102.2017.1348990. Epub 2017 Jul 13.
The pore domain of human voltage-dependent cardiac sodium channel Na1.5 (hNa1.5) is the crucial binding targets for anti-arrhythmics drugs and some local anesthetic drugs but its three-dimensional structure is still lacking. This has affected the detailed studies of the binding features and mechanism of these drugs. In this paper, we present a structural model for open-state pore domain of hNa1.5 built using single template ROSETTA-membrane homology modeling with the crystal structure of NaMs. The assembled structural models are evaluated by rosettaMP energy and locations of binding sites. The modeled structures of the pore domain of hNa1.5 in open state will be helpful to explore molecular mechanism of a state-dependent drug binding and help designing new drugs.
人源电压门控钠离子通道 Na1.5（hNa1.5）的孔域是抗心律失常药物和一些局部麻醉药物的关键结合靶标，但它的三维结构仍然缺失。这影响了这些药物结合特征和机制的详细研究。在本文中，我们使用 NaMs 的晶体结构，通过单一模板 ROSETTA-膜同源建模，构建了 hNa1.5 开放状态孔域的结构模型。通过 rosettaMP 能量和结合位点的位置对组装的结构模型进行评估。hNa1.5 开放状态孔域的建模结构将有助于探索状态依赖性药物结合的分子机制，并有助于设计新的药物。
