Structural modeling of human cardiac sodium channel pore domain

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 Nav1.5 (hNav1.5) 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 hNav1.5 built using single template ROSETTA-membrane homology modeling with the crystal structure of NavMs. The assembled structural models are evaluated by rosettaMP energy and locations of binding sites. The modeled structures of the pore domain of hNav1.5 in open state will be helpful to explore molecular mechanism of a state-dependent drug binding and help designing new drugs.

Keywords: Nav1.5 pore domain; binding sites; homology modeling; local anesthetic drugs; three-dimensional structure.

MeSH terms

  • Amino Acid Sequence
  • Binding Sites
  • Humans
  • Ligands
  • Models, Molecular*
  • Molecular Docking Simulation
  • Molecular Dynamics Simulation
  • NAV1.5 Voltage-Gated Sodium Channel / chemistry*
  • Protein Binding
  • Protein Conformation
  • Protein Domains*


  • Ligands
  • NAV1.5 Voltage-Gated Sodium Channel