Our final model (Equation ) reflects the above results. We capture the impact of the fluorination-induced differences on side chain-water interactions in two ways, via the average number of water-fluorine hydrogen bonds established by each amino acid (the h CH n F m terms, where n = 0, 1, 2 and m = 1, 2, 3, in Equation ) and via the fluorination-induced change in the number of water molecules experiencing the positive potential region of the side chain (the DF + term in Equation ). Fitting Equation 1 to the DDG Hyd data shown in Figure yields the parameters in Table ; see SI section 5.2 for details of the fit.