Electro-Wetting of a Hydrophobic Gate in a Biomimetic Nanopore

Abstract

Nanopores in membranes have a range of potential applications. Biomimetic design of nanopores aims to mimic key functions of biological pores within a stable template structure. Molecular dynamics simulations have been used test whether a simple β-barrel protein nanopore can be modified to incorporate a hydrophobic barrier to permeation. Simulations have been used to evaluate functional properties of such nanopores, using water flux as a proxy for ionic conductance. Potential of mean force calculations have been used to calculate free energy landscapes for water and for ion permeation in pore models. These studies demonstrate that a hydrophobic barrier can indeed be designed into a β-barrel protein nanopore, and that the height of the barrier can be adjusted by modifying the number of consecutive rings of hydrophobic sidechains. A hydrophobic barrier prevents both water and ion permeation even though the pore is sterically unoccluded [1].A clear prediction of the hydrophobic gating model is that of electro-wetting of the gate should occur, i.e. the pore can be functionally opened by applying a high transmembrane voltage. This has been seen experimentally in studies of hydrophobically-gated solid state nanopores [2]. We have explored electro-wetting of our model of a hydrophobic gate in a simple β-barrel protein nanopore using atomistic molecular dynamics simulations with either a constant field applied or with the recently developed ‘computational electrophysiology’ approach [3] to model a voltage difference across the pore and bilayer. The results of both methods demonstrate voltage-dependent de-wetting in these pores.1. J. Trick et al (2014). Designing Hydrophobic Barriers into Biomimetic Nanopores (submitted)2. M. R. Powell, et al. (2011). Nature Nanotechnology, 6, 798-802.3. C. Kutzner et al. (2011). Biophys J, 101, 809-817.