Molecular Selectivity in Aquaporin Channels Studied by the 3D-RISM Theory

The three-deimensional distribution functions (3D-DFs) and potentials of mean force (PMFs) of small neutral molecules inside the two aquaporin channels, AQP1 and GlpF, are calculated based on the 3D-RISM theory, the statistical mechanics theory of molecular liquids, in order to investigate the permeability of those ligands through the channels. The ligands investigated are neon (Ne), carbon dioxide (CO2), nitric oxide (NO), ammonia (NH3), urea, and glycerol. Neon shows continuous distribution throughout the channel pore in AQP1 as is the case of water, although the PMF of Ne at the selective filter (SF) region is higher than that of water, indicating that the stability of molecules in the channel is determined not only by their size, but also by the charge distribution. The ligand molecules, CO2, NO, urea, and glycerol, have a large barrier in PMF at the SF region in AQP1, indicating that the channel is not permeable by those ligands. On the other hand, NH3 has only a small activation barrier, similar to 2.5 kJ/mol, to be overcome. Therefore, our theory predicts that a NH3 molecule can be permeated through the AQP1 channel. In GlpF, all the ligands have negative PMF throughout the channel pore except for glycerol, which has a small barrier at the SF area, similar to 2.1 kJ/mol. The barrier can be readily overcome by the thermal motion. So, our results are quite consistent with the experiments for urea and glycerol, for which the corresponding data are available. The results obtained by the 3D-RISM theory show striking differences from those obtained by the MD simulations, especially in the case of GlpF. Possible causes of the difference in the results between the two methods are discussed.