Application of the Transition State Theory in the Study of the Osmotic Permeabilities of AQP7, AQP10 and GlpF

Aquaglyceroporins, including human AQP7, AQP10, and <i>E. coli</i> GlpF, are known to facilitate movements of glycerol, water, and some other uncharged molecules across the cell membrane. In this study we focused on the transport of water molecules in the absence of glycerol for AQP7, AQP10 and GlpF using the Transition State Theory for the novel application of permeability and kinetics studies. We conducted around 500 ns of in silico simulations of the aquaglyceroporins embedded in lipid bilayer membranes with intracellular-extracellular asymmetries in leaflet lipid compositions. For the water permeability analysis, we computed the transition rate constant with correction for recrossing events where the water molecules do not completely traverse the protein channel from one side of the membrane to the other side. We also studied the hydrogen bond distributions of the single-file waters and channel residues and linear water densities along the pores of the aquaglyceroporins. Interestingly, we found that there was an inverse correlation between the number of single-file water molecules in the channel and osmotic permeability.