The mechanosensitive channel of small conductance (MscS) belongs to a family of membrane proteins that are gated in response to changes in membrane tension, thereby protecting the cell from hypo-osmotic shock. Here we report on passive ion transport simulations of MscS in a POPC bilayer using a coarse-grained particle-based description based on the Boltzmann transport Monte Carlo method. Single channel current-voltage curves are computed over hundreds of nanoseconds for channel conformations derived from all-atom molecular dynamics simulations reaching an overall simulation time of over 5 μs. Channel conformations similar to that of the crystal structure exhibit low conductance, whereas conformations reached after opening the channel by means of steered molecular dynamics simulations match experimentally determined conductances. However, while experiments indicate a slight preference for anionic currents, the simulated channel strongly selects anions over cations and the direction of rectification at high voltages is opposite to what is observed in experiments. Three-dimensional maps of time-averaged ion distribution and equilibrium occupancy profiles constructed from trajectory data indicate separation of anions and cations inside and in the immediate vicinity of the large cytoplasmic domain of MscS, in accordance with earlier molecular dynamics simulations. This separation arises from the distribution of ionizable residues of MscS and suggests a specific, yet unknown, functional purpose.
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