title: Molecular dynamics study of ion transport through an open model of voltage-gated sodium channel.
abstract: Voltage-gated sodium (NaV) channels are critical in the signal transduction of excitable cells. In this work, we modeled the open conformation for the pore domain of a prokaryotic NaVchannel (NaVRh), and used molecular dynamics simulations to track the translocation of dozens of Na+ions through the channel in the presence of a physiological transmembrane ion concentration gradient and a transmembrane electrical field that was closer to the physiological one than previous studies. Channel conductance was then estimated from simulations on the wide-type and DEKA mutant of NaVRh. Interestingly, the conductivity predicted from the DEKA mutant agrees well with experimental measurement on eukaryotic NaV1.4 channel. Moreover, the wide-type and DEKA mutant of NaVRh exhibited markedly distinct ion permeation patterns, which thus implies the mechanistic difference between prokaryotic and eukaryotic NaVchannels.
authors.affiliation: MOE Key Laboratory of Bioinformatics, School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Li
authors.affiliation: MOE Key Laboratory of Bioinformatics, School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Ruining
authors.initials: R
authors.lastname: Sun
authors.affiliation: MOE Key Laboratory of Bioinformatics, School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Huihui
authors.initials: H
authors.lastname: Liu
authors.affiliation: MOE Key Laboratory of Bioinformatics, School of Life Sciences, Tsinghua University, Beijing 100084, China. Electronic address: hgong@tsinghua.edu.cn.
authors.forename: Haipeng
authors.initials: H
authors.lastname: Gong
mesh_terms: D001665:Binding Sites; D017136:Ion Transport; D008564:Membrane Potentials; D056004:Molecular Dynamics Simulation; D011487:Protein Conformation; D061566:Voltage-Gated Sodium Channels / Q000737:chemistry / Q000502:physiology*
chemical_list: D061566:Voltage-Gated Sodium Channels
keywords: Channel conductance; Ion permeation; Ion translocation; Molecular dynamics simulations; Na(V) channels