Dehydration of permeating alkali cations for CLDN15. (A–C) 40-ns trajectory analysis of voltage (−1.2 V) simulations for (A) CLDN15^WT 100 mM X⁺, (B) CLDN15^D55E 100 mM X⁺, and (C) CLDN15^D55N 100 mM X⁺ (where X⁺ is alkali cation Li⁺, Na⁺, K⁺, Rb⁺, or Cs⁺). The average and standard deviation of coordinating water molecules in the first hydration shell (purple) and oxygen atoms from protein residues (gold) across the pore axis, averaged over three channels in the unit cell.