The binding site differentiation between Ca ²⁺ and Na ⁺ in the SF region of TRPV6 in dicationic solution. (A) The contour plot of cation density on the R-z plane of the SF region of TRPV6. (B) The difference in cation density calculated by subtracting the density of the one-cation-species system from the density of the dicationic system. The peripheral (P) binding site is indicated by the red circle. (C and D) C is similar to A and D is similar to B, but for TRPV1. (E) Top view of the density map of cations in the SF region of TRPV6. The backbone of the protein is shown as the gray transparent cartoon. The density map is shown as the solid isosurface. The binding sites and key residues are labeled. Only two chains are shown for clarity. (F) Side view of E. Only one chain is shown. Binding sites are indicated by dashed rectangles. The transition probabilities of S1→S2 and P→S2 are labeled on the corresponding arrows, with yellow for Na⁺ and pink for Ca²⁺. The ion density isosurface is plotted using a threshold of 0.1 Å⁻³.