title: Steric selectivity in Na channels arising from protein polarization and mobile side chains.
abstract: Monte Carlo simulations of equilibrium selectivity of Na channels with a DEKA locus are performed over a range of radius R and protein dielectric coefficient epsilon(p). Selectivity arises from the balance of electrostatic forces and steric repulsion by excluded volume of ions and side chains of the channel protein in the highly concentrated and charged (approximately 30 M) selectivity filter resembling an ionic liquid. Ions and structural side chains are described as mobile charged hard spheres that assume positions of minimal free energy. Water is a dielectric continuum. Size selectivity (ratio of Na+ occupancy to K+ occupancy) and charge selectivity (Na+ to Ca2+) are computed in concentrations as low as 10(-5) M Ca2+. In general, small R reduces ion occupancy and favors Na+ over K+ because of steric repulsion. Small epsilon(p) increases occupancy and favors Na+ over Ca2+ because protein polarization amplifies the pore's net charge. Size selectivity depends on R and is independent of epsilon(p); charge selectivity depends on both R and epsilon(p). Thus, small R and epsilon(p) make an efficient Na channel that excludes K+ and Ca2+ while maximizing Na+ occupancy. Selectivity properties depend on interactions that cannot be described by qualitative or verbal models or by quantitative models with a fixed free energy landscape.
authors.affiliation: Department of Molecular Biophysics and Physiology, Rush University Medical Center, Chicago, Illinois, USA.
authors.forename: Dezso
authors.initials: D
authors.lastname: Boda
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Nonner
authors.forename: Mónika
authors.initials: M
authors.lastname: Valiskó
authors.forename: Douglas
authors.initials: D
authors.lastname: Henderson
authors.forename: Bob
authors.initials: B
authors.lastname: Eisenberg
authors.forename: Dirk
authors.initials: D
authors.lastname: Gillespie
mesh_terms: D001665:Binding Sites; D055592:Biophysical Phenomena; D001703:Biophysics; D002118:Calcium / Q000378:metabolism; D003198:Computer Simulation; D008954:Models, Biological; D008958:Models, Molecular; D009010:Monte Carlo Method; D018272:Porins / Q000737:chemistry / Q000378:metabolism; D011188:Potassium / Q000378:metabolism; D019837:Ryanodine Receptor Calcium Release Channel / Q000737:chemistry / Q000378:metabolism; D012964:Sodium / Q000378:metabolism; D015222:Sodium Channels / Q000737:chemistry* / Q000378:metabolism*; D055672:Static Electricity; D013816:Thermodynamics
chemical_list: C109237:OmpF protein; D018272:Porins; D019837:Ryanodine Receptor Calcium Release Channel; D015222:Sodium Channels; D012964:Sodium; D011188:Potassium; D002118:Calcium