TY - JOUR
T1 - Voltage-Gated Sodium Channels
T2 - Mechanistic Insights From Atomistic Molecular Dynamics Simulations
AU - Oakes, Victoria Jayne
AU - Furini, Simone
AU - Domene, Carmen
PY - 2016/3/14
Y1 - 2016/3/14
N2 - The permeation of ions and other molecules across biological membranes is an inherent requirement of all cellular organisms. Ion channels, in particular, are responsible for the conduction of charged species, hence modulating the propagation of electrical signals. Despite the universal physiological implications of this property, the molecular functioning of ion channels remains ambiguous. The combination of atomistic structural data with computational methodologies, such as molecular dynamics (MD) simulations, is now considered routine to investigate structure–function relationships in biological systems. A fuller understanding of conduction, selectivity, and gating, therefore, is steadily emerging due to the applicability of these techniques to ion channels. However, because their structure is known at atomic resolution, studies have consistently been biased toward K+ channels, thus the molecular determinants of ionic selectivity, activation, and drug blockage in Na+ channels are often overlooked. The recent increase of available crystallographic data has eminently encouraged the investigation of voltage-gated sodium (NaV) channels via computational methods. Here, we present an overview of simulation studies that have contributed to our understanding of key principles that underlie ionic conduction and selectivity in Na+ channels, in comparison to the K+ channel analogs.
AB - The permeation of ions and other molecules across biological membranes is an inherent requirement of all cellular organisms. Ion channels, in particular, are responsible for the conduction of charged species, hence modulating the propagation of electrical signals. Despite the universal physiological implications of this property, the molecular functioning of ion channels remains ambiguous. The combination of atomistic structural data with computational methodologies, such as molecular dynamics (MD) simulations, is now considered routine to investigate structure–function relationships in biological systems. A fuller understanding of conduction, selectivity, and gating, therefore, is steadily emerging due to the applicability of these techniques to ion channels. However, because their structure is known at atomic resolution, studies have consistently been biased toward K+ channels, thus the molecular determinants of ionic selectivity, activation, and drug blockage in Na+ channels are often overlooked. The recent increase of available crystallographic data has eminently encouraged the investigation of voltage-gated sodium (NaV) channels via computational methods. Here, we present an overview of simulation studies that have contributed to our understanding of key principles that underlie ionic conduction and selectivity in Na+ channels, in comparison to the K+ channel analogs.
U2 - 10.1016/bs.ctm.2015.12.002
DO - 10.1016/bs.ctm.2015.12.002
M3 - Article
SN - 1063-5823
JO - CURRENT TOPICS IN MEMBRANES
JF - CURRENT TOPICS IN MEMBRANES
ER -