The influence of geometry, surface character, and flexibility on the permeation of ions and water through biological pores

Abstract

A hydrophobic constriction site can act as an efficient barrier to ion and water permeation if its diameter is less than the diameter of an ion's first hydration shell. This hydrophobic gating mechanism is thought to operate in a number of ion channels, e.g. the nicotinic receptor, bacterial mechanosensitive channels (MscL and MscS) and perhaps in some potassium channels (e.g. KcsA, MthK and KvAP). Simplified pore models allow one to investigate the primary characteristics of a conduction pathway, namely its geometry (shape, pore length, and radius), the chemical character of the pore wall surface, and its local flexibility and surface roughness. Our extended (about 0.1 micros) molecular dynamic simulations show that a short hydrophobic pore is closed to water for radii smaller than 0.45 nm. By increasing the polarity of the pore wall (and thus reducing its hydrophobicity) the transition radius can be decreased until for hydrophilic pores liquid water is stable down to a radius comparable to a water molecule's radius. Ions behave similarly but the transition from conducting to non-conducting pores is even steeper and occurs at a radius of 0.65 nm for hydrophobic pores. The presence of water vapour in a constriction zone indicates a barrier for ion permeation. A thermodynamic model can explain the behaviour of water in nanopores in terms of the surface tensions, which leads to a simple measure of 'hydrophobicity' in this context. Furthermore, increased local flexibility decreases the permeability of polar species. An increase in temperature has the same effect, and we hypothesize that both effects can be explained by a decrease in the effective solvent-surface attraction which in turn leads to an increase in the solvent-wall surface free energy.

One-microsecond molecular dynamics simulation of channel gating in a nicotinic receptor homologue

“…A hydrophobically gated channel is expected to show at least partial dehydration, thus disrupting the connection between intra-and extracellular media (34). This disruption is precisely what happens here (Fig.…”

Ion exclusion by sub-2-nm carbon nanotube pores

“…On the contrary, entrance into subnanometer CNT imposes a high energy penalty because it requires losing part of the hydration shell. MD simulations for other hydrophobic nanopores used as models for biological nanochannels (42,43) reach similar conclusions. For charged CNTs, theoretical efforts have focused on understanding ion transport through subnanometer CNT and under an external electric field.…”

Electric-field-controlled water and ion permeation of a hydrophobic nanopore

“…The nanopores will be assumed to be cylinders with smooth surfaces connecting two reservoirs with aqueous solutions. Under equilibrium conditions, in the absence of ions, this simple model has been shown to share with more realistic models of carbon nanotubes 5 or of hydrophobic ion channels [6][7][8][9] the phenomenon of intermittent filling by water or "liquid/vapor oscillations" of the confined water over a narrow range of pore diameters. 10 This intermittent behavior may provide a gating mechanism for hydrophobic ion channels, whereby the channel is open or closed to ion transport when it is filled or empty of water, 8 a scenario for which some recent experimental evidence has become available.…”