Figure 3.

Simplified models considered for analysis. (A and B). Minimal model of the binding site NA1 (A) and NA2 (B), where all ligands are allowed to move freely within a sphere of 3.5 Å radius (indicated by dashed line). The calculated free energies ΔΔG is 2.41 kcal/mol for NA1 (A) and −0.3 kcal/mol for NA2 (B). (C) Na+-selective toy-model of the binding site NA2 described in the text. The calculated free energy is 1.49 kcal/mol when all functional groups within the 3.5 radii are allowed to fluctuate freely, while the outside groups were frozen.