(A) Cross-section of the c10-ring of the mitochondrial ATP synthase from S. cerevisiae. The surface of the protein is colored as follows: Lys and Arg, blue; Asp and Glu, red; other polar residues (and protonated Glu), green; other residues, grey. The ring is oriented such that the interface with the F1 domain, inside the mitochondrial matrix, is up. (B) Molecular simulation system employed to study the properties of the c10-ring, shown again in cross-section (blue). The ring is embedded in a model phospholipid bilayer, in 100 mM KCl. K+ and Cl- ions are shown as yellow and green spheres, respectively. Note the c-ring lumen is hydrated. (C, D) Potential-of-mean-force (G(z), PMF) and diffusion-coefficient profiles for the permeation of either K+ or Cl- across the lumen of the c10-ring (Materials and methods). The lack of binding sites for K+ and the 3 kcal/mol free-energy barrier explain the modest K+ conductance; permeation by Cl-, by contrast, is strongly favored electrostatically. (E, F) Same as (A, B), for a variant of the c13-ring from Bacillus pseudofirmus (Figure 1—figure supplement 2B,C), whose lumen is wider than that of the c10-ring. (G) Free-energy of selectivity for Cl- and against K+ by the c10-ring lumen, examined with and without electrolyte. The selectivity profile, ΔG(z), was calculated by subtracting the individual PMF profiles, G(z), in each case. The marked increase in Cl- selectivity toward the lumen entrance, on the matrix side, confirms the strong electrostatic influence of a ring of arginine residues. (H) Same as (G), for the variant of the c13-ring from B. pseudofirmus. Despite its wider lumen, this ring is also markedly anion selective, unlike the MPTP.