Reduced CLDN15 model allows for analysis of pore permeability properties. (A) Snapshot of the full CLDN15 model. The model contains two parallel lipid bilayers (green) and three CLDN15 pores in the unit cell. Na⁺ and Cl^- ions are represented in red and gray, respectively. The white dotted lines indicate the section of protein removed in preparation for the reduced model. (B) View of the channels in the reduced CLDN15 model, in which the TM helices and two lipid bilayers have been entirely removed. There is ∼15 Å of vacuum above and below the water slab, and the water molecules in the slab are constrained to their initial volume, preventing them from diffusing into the vacated membrane region. This model includes the ion conduction pores, surrounding solutions, and part of the TM helices. (C) Side view of the reduced system model after a 90° counterclockwise rotation. The solutions on the two sides represent apical and basolateral solutions; however, it must be noted that the channel is symmetric along the pore. (D) Cations used in comparative simulations, plotted by size in Angstroms.