# The Molecular Mechanism of Ion Selectivity in Nanopores

## TL;DR

This paper investigates how nanopores selectively allow certain ions to pass through by analyzing the role of hydration and hydrophobic interactions.

## Contribution

The study introduces a novel framework for understanding ion selectivity based on hydration layer rearrangement and energy barriers.

## Key findings

- Ion selectivity in nanopores is influenced by the energy barrier related to ion size and pore radius.
- Hydrophobic interactions and hydration layer changes play a key role in ion selectivity.
- Potential mean force calculations via MD simulations support the proposed mechanism.

## Abstract

Ion channels exhibit strong selectivity for specific ions over others under electrochemical potentials, such as KcsA for K+ over Na+. Based on the thermodynamic analysis, this study is focused on exploring the mechanism of ion selectivity in nanopores. It is well known that ions must lose part of their hydration layer to enter the channel. Therefore, the ion selectivity of a channel is due to the rearrangement of water molecules when entering the nanopore, which may be related to the hydrophobic interactions between ions and channels. In our recent works on hydrophobic interactions, with reference to the critical radius of solute (Rc), it was divided into initial and hydrophobic solvation processes. Additionally, the different dissolved behaviors of solutes in water are expected in various processes, such as dispersed and accumulated distributions in water. Correspondingly, as the ion approaches the nanopore, there seems to exist the “repulsive” or “attractive” forces between them. In the initial process (<Rc), the energy barrier related to “repulsive” force may be expected as ions enter the channel. Regarding the ion selectivity of nanopores, this may be due to the energy barrier between the ion and channel, which is closely related to the ion size and pore radius. Additionally, these may be demonstrated by the calculated potential mean forces (PMFs) using molecular dynamics (MD) simulations.