Osmotic permeability in a molecular dynamics simulation of water transport through a single-occupancy pore

Abstract

The aim of this work is to determine plausible values for the rate constants of kinetic models representing water transport through narrow pores. We present here the results of molecular dynamics simulations of the movement of water molecules through a single-site hydrophilic pore. The system consists of a rectangular box of water molecules, some of which are positionally restrained so as to act as a membrane. This membrane separates two compartments where water molecules move freely; one of the positions in the membrane is initially vacant (the ‘single-site pore’), but can be occupied by mobile molecules. To analyze the results, we represented the pore by a two-state kinetic diagram in which the vacant and occupied states are linked by transitions corresponding to the binding and release of water molecules. The mean occupancy and vacancy times directly yield the rate constants of binding and release, which in turn yield the osmotic water permeability coefficient per pore p f. We also compute the apparent activation energies ΔE ∗ for the rate constants and for p f The p f value was (1.56 ± 0.04) · 10 −11cm 3/s (at 307 K), which is much larger than those determined for CHIP28 and for gramicidin A (of about 10 −13and 10 −14cm 3/s, respectively). These values were compared with those arising from a model of a symmetric single-file pore through which one-vacancy-mediated water transport takes place. The model yields an expression for p f as a function of the rate constants and of the number of molecular positions ( n) in the file. When n = 1, this expression becomes the one corresponding to the single-site pore studied in our current simulation. Using the rate constants of binding and release derived from our simulation, the p f values are consistent with an occupancy value of 5–6 found for gramicidin A, and with occupancies of 4–7 that can be estimated for the single-file pore of a recently proposed model for CHIP28. ΔE ∗ for p f is 3.0 kcal/mol, a value similar to that determined for CHIP28. Hence, the system simulated here appears plausible and can be used to mimic some physical properties of water transport through biological pores.