Molecular dynamics studies with custom-tailored force fields and phenomenological models based on discrete rather than mean-field descriptors are key to gain mechanistic insight on solvation, as exemplified in this work. The force field and model we present lay the foundation to interpret how fluorination alters the hydrophobicity of other (bio)polymers. Further improving these force fields and our understanding of solvation will require the experimental measurement of free energies of hydration for amino acids or molecules of similar complexity. If the vapor pressure of the pure compound in liquid form is known together with its aqueous solubility, the free energy of hydration can be immediately calculated assuming ideality . We deliberately restricted our study to amino acids for which synthesis protocols exist , and we hope that a direct comparison between experiment and simulation will be possible in the future.