Dynamics of ions in the selectivity filter of the KcsA channel: Towards a coupled Brownian particle description

TL;DR

This paper investigates ion dynamics in the KcsA channel's selectivity filter using molecular dynamics simulations and proposes a new Brownian dynamics model, highlighting the impact of different assumptions on ion behavior and potential energy profiles.

Contribution

It introduces a novel approach to derive Brownian dynamics models from unbiased MD simulations and compares different Langevin equation formulations for ion motion.

Findings

Ion dynamics can be modeled by under-damped Langevin equations or fractional memory kernels.

Significant differences found between potentials of mean force from unbiased MD and umbrella sampling.

Open questions remain about the origins of discrepancies in potential energy profiles.

Abstract

The statistical and dynamical properties of ions in the selectivity filter of the KcsA ion channel are considered on the basis of molecular dynamics (MD) simulations of the KcsA protein embedded in a lipid membrane surrounded by an ionic solution. A new approach to the derivation of a Brownian dynamics (BD) model of ion permeation through the filter is discussed, based on unbiased MD simulations. It is shown that depending on additional assumptions, ion's dynamics can be described either by under-damped Langevin equation with constant damping and white noise or by Langevin equation with a fractional memory kernel. A comparison of the potential of the mean force derived from unbiased MD simulations with the potential produced by the umbrella sampling method demonstrates significant differences in these potentials. The origin of these differences is an open question that requires further clarifications.