Change in DG Hyd with fluorination depends on the chirality and location of the fluorinated site and on amino acid identity. We calculated hydration free energies as a measure of the hydrophobicity of 16 fluorinated amino acids and their 5 nonfluorinated counterparts, totaling 21 aliphatic amino acids (see Figure ). These free energies are shown in SI Table and Figure ; we reported some of these values in a prior publication . The DDG Hyd values have an associated standard deviation of 0.1 to 0.3 kcal mol 1 (see SI Table ), enabling the precise detection of differences between amino acids.