Theory and Simulation of Water Permeation in Aquaporin-1

Abstract

We discuss the difference between osmotic permeability p f and diffusion permeability p d of single-file water channels and demonstrate that the p f/ p d ratio corresponds to the number of effective steps a water molecule needs to take to permeate a channel. While p d can be directly obtained from equilibrium molecular dynamics simulations, p f can be best determined from simulations in which a chemical potential difference of water has been established on the two sides of the channel. In light of this, we suggest a method to induce in molecular dynamics simulations a hydrostatic pressure difference across the membrane, from which p f can be measured. Simulations using this method are performed on aquaporin-1 channels in a lipid bilayer, resulting in a calculated p f of 7.1 × 10 −14 cm 3/s, which is in close agreement with observation. Using a previously determined p d value, we conclude that p f/ p d for aquaporin-1 measures ∼12. This number is explained in terms of channel architecture and conduction mechanism.