Simulating Current-Voltage Relationships for a Simple Ion Channel with All-Atom Resolution using the Weighted Ensemble Method

Abstract

The use of brute-force, fully atomistic simulation to recreate ion channel current-voltage curves remains computationally challenging. To overcome this shortcoming, we developed a rare-event sampling approach that applies the Weighted Ensemble (WE) method to study single file ion movement through individual ion channels. Our method makes it possible to calculate the current through the channel induced by the application of an external electric field. Additionally, WE produces a representative sample of continuous trajectories in the transition ensemble, allowing for the analysis of the permeation mechanism in full atomistic detail. We demonstrate the applicability of this method to a model cation-selective biological membrane channel embedded in a bath of SPC/E water at different ionic concentrations and applied voltages. Comparison to long brute-force dynamics shows that the method rigorously reproduces the correct voltage-current relationship. This work sets the foundation for application of this methodology to more complex, biological channels as well as other non-equilibrium transport phenomena.