Binding free energy parameter grids used to reduce parameter search space and identify χ2 minima. (A) Grid of coupling free energy (ΔGγ) versus the free energy of binding to a reference state with no occupied neighbors (ΔG0), for the six-parameter additive model. (Blue cross) Global minimum. (B) Coupling free energies for the nine-parameter model of nonadditive cooperativity, of sites flanked by one (ΔGoe) and two (ΔGoo) occupied neighboring sites, versus the reference state ΔG0. (Red crosses) Values of fits to 50 random bootstrap datasets were used to estimate parameter uncertainties, using the grid minimum as a starting point. To see this figure in color, go online.