Soft‐wall ion transfer channel accurately predicts sterically hindered ion channel permeability

Abstract

We provide a simple and systematic computational model to study ion channel permeability using density functional theory. While existing permeability models with a hard-wall steric hindrance factor work reasonably well for large ions, they severely inhibit the permeation of small ions through channel pores.Here, by introducing a steric hindrance factor that allows pore expansion due to intrinsically soft ion transfer channel walls, the new permeability model accurately describes the effect of steric hindrance stemming from the soft and flexible ion channel wall. Most importantly, the soft-wall ion transfer channel model works for a wide range of ionic radii from fluoride to gluconate. In addition, we show that strong local electrostatic interaction between densely charged ions such as fluoride and bicarbonate and ion channels with ion binding sites significantly promotes the permeation processes. K E Y W O R D S density functional theory (DFT), ion channel permeability, soft-wall ion transfer channel (SWITCH)