Structural modeling of Na<sub>v</sub>1.5 pore domain in closed state

Xiaofeng Ji; Yanzhao Huang; Jun Sheng

doi:10.52601/bpr.2021.200021

Volume 7 Issue 4

Sep. 2021

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Xiaofeng Ji, Yanzhao Huang, Jun Sheng. Structural modeling of Nav1.5 pore domain in closed state[J]. Biophysics Reports, 2021, 7(4): 341-354. doi: 10.52601/bpr.2021.200021

Citation:

Xiaofeng Ji, Yanzhao Huang, Jun Sheng. Structural modeling of Na_v1.5 pore domain in closed state[J]. Biophysics Reports, 2021, 7(4): 341-354. doi: 10.52601/bpr.2021.200021

Xiaofeng Ji, Yanzhao Huang, Jun Sheng. Structural modeling of Nav1.5 pore domain in closed state[J]. Biophysics Reports, 2021, 7(4): 341-354. doi: 10.52601/bpr.2021.200021

Citation:

Xiaofeng Ji, Yanzhao Huang, Jun Sheng. Structural modeling of Na_v1.5 pore domain in closed state[J]. Biophysics Reports, 2021, 7(4): 341-354. doi: 10.52601/bpr.2021.200021

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Structural modeling of Na_v1.5 pore domain in closed state

doi: 10.52601/bpr.2021.200021

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

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

More Information

Corresponding author: jixf@ysfri.ac.cn (X. Ji)
Received Date: 28 June 2020
Accepted Date: 21 July 2021
Publish Date: 17 September 2021

Abstract

Abstract

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 Na_v1.5 pore domain in closed state. The structure was constructed by Rosetta-membrane homology modeling method based on the template of eukaryotic Na_v channel Na_vPaS 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 Na_v1.5 pore domain in closed state may be useful to explore molecular mechanism of a state-dependent drug binding and helpful for new drug development.
- Na_v1.5 ion channel,
- Closed state,
- Homology modeling,
- Direct coupling analysis,
- Local anesthetics,
- Drug binding

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References(45)

References

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