A User-Friendly Computational Tool for Markov Modelling Channel Gating and Transport Cycling

Abstract

The behavior of ion channels and transporters is often modelled using discrete-state continuous-time Markov models. Such models are helpful for the interpretation of experimental data and can guide the design of experiments by testing specific predictions. Here, we present a computational tool that allows to create Markov models of chosen complexity, and to calculate their predictions on a macroscopic as well on a single-molecule scale. The program (https://github.com/mikpusch/MarkovEditor) calculates steady-state properties (current, state-probabilities, cycle frequencies), deterministic macroscopic and stochastic time courses, gating currents, dwell time histograms, and power spectra of channels and transporters. In addition, a visual simulation mode allows to follow the time-dependent stochastic behavior of a single channel or transporter. After a basic introduction into the concept of Markov models, real-life examples are discussed, including a model of a simple K+ channel, a voltage-gated sodium channel, a three-state ligand-gated channel, and an electrogenic uniporter. The MarkovEditor program can serve students to explore Markov models at a basic level, but is also suited for research scientists to test and develop models on the mechanisms of protein function.