Current–Voltage Characteristics of K+ Channels Estimated by MD Simulations and Markov State Models

Due to their high computational cost, MD simulations are typically performed at membrane potentials well above physiological values, and at only a limited number of voltages. Since current–voltage relationships are not necessarily linear, this limits direct comparison between simulations and experiments.

Here, we introduce a method to estimate the current–voltage characteristics of ion channels from Markov state models (MSMs) constructed from MD simulations performed at only few membrane potentials. Time-discrete MSMs of ion conduction are converted into continuous-time rate matrices, whose voltage dependence is modeled using a rate theory formulation with free energy barriers depending on membrane potential. This approach enables the prediction of channel currents over a wide voltage range without additional simulations.