With the rapid development of biological technology and membrane synthesis, water industries have inclined towards biomimetic membranes for water purification and desalination. Aquaporin (AQP) embedded synthetic membranes seem to be promising due to the AQP's high selectivity and permeability, however, the effect of inherent membranous residual stress on protein structure and water permeation has been rarely studied yet and remains unclear. Here, we studied water permeability through the tetrameric human AQP1, embedded in a POPC lipid bilayer, under lateral mechanical stimuli using all-atom molecular dynamics simulations. Four different systems were studied where different stimuli were applied to the simulation cell. By counting the permeation events, we found that radially stretching protein though opens up and widens the pore in the planar direction; it reduced the final permeability compared to control. The hydrostatic pressure stimulus system possesses the highest permeability coefficient followed by the protein compressing system. By screening the water occupancy and pore-lining residues in different systems, we found that stretching the protein increased the dynamics of the pore-lining residues which interrupts the single-file line of water molecules in the pore, hence reducing the likelihood of water molecules to pass the pore. We also observed that the constriction site is located where the two pore-lining residues of ASN76 and ILE 60 meet. Our result provides a benchmark for designing a more efficient membrane desalination system for the treatment of water worldwide.
