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

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. Employing Langevin simulations taking into account an external electric field predicts macroscopic observables in the form of I-V characteristics, which exhibit good agreement with their experimental counterparts, but highlight the necessity to include polarization effects in ion diffusion simulations.