Modeling the human Na_v1.5 sodium channel: structural and mechanistic insights of ion permeation and drug blockade.

ABSTRACT: Abnormalities in the human Na_v1.5 (hNa_v1.5) voltage-gated sodium ion channel (VGSC) are associated with a wide range of cardiac problems and diseases in humans. Current structural models of hNa_v1.5 are still far from complete and, consequently, their ability to study atomistic interactions of this channel is very limited. Here, we report a comprehensive atomistic model of the hNa_v1.5 ion channel, constructed using homology modeling technique and refined through long molecular dynamics simulations (680 ns) in the lipid membrane bilayer. Our model was comprehensively validated by using reported mutagenesis data, comparisons with previous models, and binding to a panel of known hNa_v1.5 blockers. The relatively long classical MD simulation

SUBMITTER: Ahmed M 

PROVIDER: S-EPMC5552146 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature