The potential of mean force of water and ions in aquaporin channels investigated by the 3D-RISM method

The three dimensional (3D) distributions of sodium, chloride, and hydronium ions along with water, in two aquaporin channels, AQP1 and GlpF, were calculated using the three dimensional reference interaction site model (3D-RISM) theory. It was found from the potential of mean force (PMF) obtained from the 3D-distribution that water inside the both channels is slightly more stable than bulk, and that PMF does not have high barriers for a water molecule to cross. The results are completely in harmony with the experimental observations, while they are in accord with none of the molecular simulation studies. All the ions studied are hard to permeate through either of the channels. However, the reasons why the permeability is so low are different depending on the channels and the ions. In the AQP1 channel, the cations, or Na+ and H3O+, are largely excluded from the channel essentially by the electrostatic repulsion due to the positively charged residues, while the Cl− ion is blocked by a high steric barrier at the selective filter (SF) region. In the GlpF, the PMFs of Na+ and H3O+ inside the channel are mostly positive, and they have three large barriers to cross, which may be preventing the ions from permeation. On the other hand, the PMF of Cl− is largely negative, but it has wide and deep well which likely prevents the ion from permeating through the channel by “trapping” mechanism.