The flexibility of the pore helix influences the cation permeation of TRPV channels. (A) A representative simulation system, which contains the full TRPV6 (green cartoon) embedded in a POPC bilayer (gray surface). The multisite Ca²⁺ ions are shown as blue spheres and Cl⁻ as orange spheres. Water molecules are filled in the box but not shown for clarity. (B) The structure of the SF region of TRPV6. The backbone of protein is shown as a cartoon with the pore helix and loops shown as solid and other parts as transparent. Key residues forming the SF are shown as licorice and labeled. Only two chains are shown for clarity. (C) The average pore radius of the SF region of TRPV6 during simulations with different restraints. The standard deviation is shown as the shaded area. (D) The cumulative number of Na⁺ permeation events (N_Event) during simulations with different restraints. The ion conductances calculated based on the number of permeation events were labeled. (E–G) Similar to B–D, respectively, but for TRPV1. The solid lines correspond to the average conductance from three independent simulation trajectories represented by dash lines.