The 20-particle model (Scheme 5). (A) Cartoon of particles and interactions, including the tetrameric pore. (B) Energy landscape of the pore demonstrates three energy tiers separated by approximately −ΔWB. The lowest tiers are the closed and open states, shown symbolically as four squares (resting P particles) and four circles (activated P particles). The intermediate states, characterized by imbalances in the number of activated P particles (energy = ΔGP − ΔWB) and P–P interactions (solid connector lines; energy = ΔWB), represent the activation pathway for opening. The highest energy state, the p = 2 trans-configuration, which has two activated P particles but no P–P interactions, would rarely be visited. (C) Conductance Hill plot for the tetrameric pore (solid lines, ΔWB = −250 meV; dashed lines are the linkage curves for the two-state pore). (D) Same as in C but on an expanded V axis, with asymptotes drawn as thin dashed lines and interaction energies indicated by arrows. The dotted rectangle shows the boundaries of the plot in C.