Structural modeling of human cardiac sodium channel pore domain

The pore domain of human voltage-dependent cardiac sodium channel Na_v1.5 (hNa_v1.5) 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 hNa_v1.5 built using single template ROSETTA-membrane homology modeling with the crystal structure of Na_vMs. The assembled structural models are evaluated by rosettaMP energy and locations of binding sites. The modeled structures of the pore domain of hNa_v1.5 in open state will be helpful to explore molecular mechanism of a state-dependent drug binding and help designing new drugs.