Computational modeling provides atomic-level insights into how antiarrhythmic drugs interact with cardiac sodium channels, which may aid future rational drug design.
Significance Voltage-gated sodium channels play a central role in cellular excitability and are key targets for drug development. Recent breakthroughs in high-resolution cryo-electron microscopy protein structure determination, Rosetta computational protein structure modeling, and multimicrosecond molecular dynamics simulations are empowering advances in structural biology to study the atomistic details of channel−drug interactions. We used Rosetta structural computational modeling and molecular dynamics simulations to study the interactions of antiarrhythmic and local anesthetic drugs with cardiac sodium channel. Our results provide crucial atomic-scale mechanistic insights into the channel–drug interactions, necessary for the rational design of novel modulators of the human cardiac sodium channel to be used for the treatment of cardiac arrhythmias.
Nguyen et al. (Wed,) studied this question.