Influence of effective polarization on ion and water interactions within a biomimetic nanopore

Abstract

Interactions between ions and water at hydrophobic interfaces within ion channels and nanopores are suggested to play a key role in the movement of ions across biological membranes. Previous molecular-dynamics simulations have shown that anion affinity for aqueous/hydrophobic interfaces can be markedly influenced by including polarization effects through an electronic continuum correction. Here, we designed a model biomimetic nanopore to imitate the polar pore openings and hydrophobic gating regions found in pentameric ligand-gated ion channels. Molecular-dynamics simulations were then performed using both a non-polarizable force field and the electronic-continuum-correction method to investigate the behavior of water, Na⁺, and Cl^- ions confined within the hydrophobic region of the nanopore. Number-density distributions revealed preferential Cl^- adsorption to the hydrophobic pore walls, with this interfacial layer largely devoid of Na⁺. Free-energy profiles for Na⁺ and Cl^- permeating the pore also display an energy-barrier reduction associated with the localization of Cl^- to this hydrophobic interface, and the hydration-number profiles reflect a corresponding reduction in the first hydration shell of Cl^-. Crucially, these ion effects were only observed through inclusion of effective polarization, which therefore suggests that polarizability may be essential for an accurate description for the behavior of ions and water within hydrophobic nanoscale pores, especially those that conduct Cl^-.