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 (MD) simulations have shown that the affinity of polarizable anions to aqueous/hydrophobic interfaces can be markedly influenced by including polarization effects through an electronic continuum correction (ECC). Here, we designed a model biomimetic nanopore to imitate the polar pore openings and hydrophobic gating regions found in pentameric ligand-gated ion channels. MD simulations were then performed using both a non-polarizable force field and the ECC 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-.

Influence of Electronic Polarization on the Binding of Anions to a Chloride-Pumping Rhodopsin

“…This suggests that it is more favourable for Clˉ to associate with these hydrophobic contacts (8). These Clˉ preferences were achieved through the partial loss of hydration shell; an effect that was previously observed for Clˉ ions in a model hydrophobic nanopore (9). As a consequence of including polarization and the resulting induced dipoles, the balance between ion-water and ion-protein interactions therefore shifts towards favouring the interactions with the hydrophobic protein contacts over water.…”

“…Interactions between the dipole and surrounding water molecules then compensate for the partial reduction in hydration in the interfacial layer, allowing Cl − to come into direct contact with the hydrophobic interface (8). Partial removal of water from the first hydration shell of Cl − is considered energetically favorable (7, 9); this phenomenon not only applies to Cl − but also to ions across the Hofmeister series, i.e., F − < Cl − < Br − < I − . The smaller, less polarizable F − generally retains its hydration shell and is unlikely to be found at aqueous/hydrophobic interfaces whereas larger, more polarizable anions such as Br − and I − are more easily dehydrated and localize at the interface (9, 10).…”

“…Partial removal of water from the first hydration shell of Cl − is considered energetically favorable (7, 9); this phenomenon not only applies to Cl − but also to ions across the Hofmeister series, i.e., F − < Cl − < Br − < I − . The smaller, less polarizable F − generally retains its hydration shell and is unlikely to be found at aqueous/hydrophobic interfaces whereas larger, more polarizable anions such as Br − and I − are more easily dehydrated and localize at the interface (9, 10). This is supported by experimental studies which indicate that the larger the halide ion, the larger the magnitude of surface adsorption to hydrophobic surfaces and hence change in water structure (11, 12).…”

“…The role of hydrophobic contacts with anions has been investigated in several recent simulation studies using a range of force fields (7, 9, 18). In particular, ongoing work on force field design has yielded hybrid methods that possess the computational efficiency of standard non-polarizable force fields yet contain parameterizations that better represent electronic responses within a mean field framework.…”

Nanopore Sensing Technique for Studying the Hofmeister Effect

“…Besides, interestingly, some recent works revealed the polarization effect in studying the short-range ion-ion and ion-water interactions using electronic continuum correction(ECC). [78,79] The work from Tucker and Sansom indicated that Cladsorption to hydrophobic pore walls occurred largely unaccompanied by Na + in the interfacial layer of the nanopore system. In particular, such ion effects were observed only when effective polarization was included.…”