title: Conduction in a biological sodium selective channel.
abstract: The crystal structure of NavAb, a bacterial voltage gated Na(+) channel, exhibits a selectivity filter (SF) wider than that of K(+) channels. This new structure provides the opportunity to explore the mechanism of conduction and help rationalize its selectivity for sodium. Recent molecular dynamics (MD) simulations of single- and two-ion permeation processes have revealed that a partially hydrated Na(+) permeates the channel by exploring three SF binding sites while being loosely coupled to other ions and/or water molecules; a finding that differs significantly from the behavior of K(+) selective channels. Herein, we present results derived from a combination of metadynamics and voltage-biased MD simulations that throws more light on the nature of the Na(+) conduction mechanism. Conduction under 0 mV bias explores several distinct pathways involving the binding of two ions to three possible SF sites. While these pathways are very similar to those observed in the presence of a negative potential (inward conduction), a completely different mechanism operates for outward conduction at positive potentials.
authors: Laboratório de Biofísica Teórica e Computacional, Departamento de Biologia Celular, Universidade de Brasília DF, Brasil.
authors: Letícia
authors: L
authors: Stock
authors: Lucie
authors: L
authors: Delemotte
authors: Vincenzo
authors: V
authors: Carnevale
authors: Werner
authors: W
authors: Treptow
authors: Michael L
authors: ML
authors: Klein
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry*; D001665:Binding Sites; D002414:Cations, Monovalent; D015640:Ion Channel Gating; D017136:Ion Transport; D007700:Kinetics; D056004:Molecular Dynamics Simulation; D011485:Protein Binding; D011487:Protein Conformation; D011789:Quantum Theory; D012964:Sodium / Q000737:chemistry*; D013816:Thermodynamics; D061566:Voltage-Gated Sodium Channels / Q000737:chemistry*; D014867:Water / Q000737:chemistry*
chemical_list: D001426:Bacterial Proteins; D002414:Cations, Monovalent; D061566:Voltage-Gated Sodium Channels; D014867:Water; D012964:Sodium