Key result
The Weighted ensemble sampling approach rigorously reproduced the correct long-time scale kinetics of a model ion channel using significantly less aggregate simulation time than brute force methods.
The Weighted Ensemble method provides a computationally efficient approach to simulate long-time scale kinetics and current-voltage relationships in narrow ion channels.
May advance ion channel simulations; leaves open links to clinical electrophysiology.
Ion channels are responsible for a myriad of fundamental biological processes via their role in controlling the flow of ions through water-filled membrane-spanning pores in response to environmental cues. Molecular simulation has played an important role in elucidating the mechanism of ion conduction, but connecting atomistically detailed structural models of the protein to electrophysiological measurements remains a broad challenge due to the computational cost of reaching the necessary time scales. Here, we introduce an enhanced sampling method for simulating the conduction properties of narrow ion channels using the Weighted ensemble (WE) sampling approach. We demonstrate the application of this method to calculate the current–voltage relationship as well as the nonequilibrium ion distribution at steady-state of a simple model ion channel. By direct comparisons with long brute force simulations, we show that the WE simulations rigorously reproduce the correct long-time scale kinetics of the system and are capable of determining these quantities using significantly less aggregate simulation time under conditions where permeation events are rare.
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Adelman et al. (2015) studied this question. Weighted ensemble (WE) sampling approach vs. Long brute force simulations was evaluated on Current-voltage relationship and nonequilibrium ion distribution at steady-state. The Weighted ensemble sampling approach rigorously reproduced the correct long-time scale kinetics of a model ion channel using significantly less aggregate simulation time than brute force methods.
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