Water and Deuterium Oxide Permeability through Aquaporin 1: MD Predictions and Experimental Verification

Determining the mechanisms of flux through protein channels requires a combination of structural data, permeability measurement, and molecular dynamics (MD) simulations. To further clarify the mechanism of flux through aquaporin 1 (AQP1), osmotic p_f (cm³/s/pore) and diffusion p_d (cm³/s/pore) permeability coefficients per pore of H₂O and D₂O in AQP1 were calculated using MD simulations. We then compared the simulation results with experimental measurements of the osmotic AQP1 permeabilities of H₂O and D₂O. In this manner we evaluated the ability of MD simulations to predict actual flux results. For the MD simulations, the force field parameters of the D₂O model were reparameterized from the TIP3P water model to reproduce the experimentally observed difference in the bulk self diffusion constants of H₂O vs. D₂O. Two MD systems (one for each solvent) were constructed, each containing explicit palmitoyl-oleoyl-phosphatidyl-ethanolamine (POPE) phospholipid molecules, solvent, and AQP1. It was found that the calculated value of p_f for D₂O is ∼15% smaller than for H₂O. Bovine AQP1 was reconstituted into palmitoyl-oleoyl-phosphatidylcholine (POPC) liposomes, and it was found that the measured macroscopic osmotic permeability coefficient P_f (cm/s) of D₂O is ∼21% lower than for H₂O. The combined computational and experimental results suggest that deuterium oxide permeability through AQP1 is similar to that of water. The slightly lower observed osmotic permeability of D₂O compared to H₂O in AQP1 is most likely due to the lower self diffusion constant of D₂O.