Predicting ion channel conductance via dissipation-corrected targeted molecular dynamics and Langevin equation simulations

TL;DR

This study combines dissipation-corrected targeted molecular dynamics with Langevin simulations to predict ion channel conductance, revealing coupled protein-ion dynamics and accurately modeling I-V characteristics.

Contribution

It introduces a novel approach integrating dissipation correction and Langevin simulations for detailed ion channel conductance prediction.

Findings

Coupled protein-ion dynamics during ion transfer.

Dissipation-corrected free energy profiles match other biased methods.

External electric field enables prediction of I-V characteristics.

Abstract

Ion channels are important proteins for physiological information transfer and functional control. To predict the microscopic origins of their voltage-conductance characteristics, we here applied dissipation-corrected targeted Molecular Dynamics in combination with Langevin equation simulations to potassium diffusion through the Gramicidin A channel as a test system. Performing a non-equilibrium principal component analysis on backbone dihedral angles, we find coupled protein-ion dynamics to occur during ion transfer. The dissipation-corrected free energy profiles correspond well to predictions from other biased simulation methods. The incorporation of an external electric field in Langevin simulations enables the prediction of macroscopic observables in the form of I-V characteristics.