Protonation state of inhibitors determines interaction sites within voltage-gated sodium channels.

ABSTRACT: Voltage-gated sodium channels are essential for carrying electrical signals throughout the body, and mutations in these proteins are responsible for a variety of disorders, including epilepsy and pain syndromes. As such, they are the target of a number of drugs used for reducing pain or combatting arrhythmias and seizures. However, these drugs affect all sodium channel subtypes found in the body. Designing compounds to target select sodium channel subtypes will provide a new therapeutic pathway and would maximize treatment efficacy while minimizing side effects. Here, we examine the binding preferences of nine compounds known to be sodium channel pore blockers in molecular dynamics simulations. We use the approach of replica exchange solute tempering (REST) to gain a more complete understa

SUBMITTER: Buyan A 

PROVIDER: S-EPMC5889629 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature