Validating a Coarse-Grained Voltage Activation Model by Comparing Its Performance to the Results of Monte Carlo Simulations.

Simulating the nature of voltage-activated systems is a problem of major current interest, ranging from the action of voltage-gated ion channels to energy storage batteries. However, fully microscopic converging molecular simulations of external voltage effects present a major challenge, and macroscopic models are associated with major uncertainties about the dielectric treatment and the underlying physical basis. Recently we developed a coarse-grained (CG) model that represents explicitly the electrodes, the electrolytes, and the membrane/protein system. The CG model provides a semimacroscopic way of capturing the microscopic physics of voltage-activated systems. Our method was originally validated by reproducing macroscopic and analytical results for key test cases and then used in modeling voltage-activated ion channels and related problems. In this work, we further establish the reliability of the CG voltage model by comparing it to the results of Monte Carlo (MC) simulations with a microscopic electrolyte model. The comparison explores different aspects of membrane, electrolyte, and electrode systems ranging from the Gouy-Chapman model to the determination of the electrolyte charge distribution in the solution between two electrodes (without and with a separating membrane), as well as the evaluation of gating charges. Overall the agreement is very impressive. This provides confidence in the CG model and also shows that the MC model can be used in realistic simulation of voltage activation of membrane proteins with sufficient computer time.