Structural modeling of human cardiac sodium channel pore domain.

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.