We searched for correlations between the information contained in the RDFs, in the form of To assess whether fluorination changes the occurrence of backbone-water hydrogen bonds by steric blockage, we calculated the distances between the carbon atom in a methyl or a fluoromethyl group (for example, C g in the ethylglycine series, C d in the leucine series) and the center of mass of either the carbonyl or amine group bound to the alpha carbon. The probability distributions for ETG (SI Figure ) show that the side chain adopts a preferred conformation relative to the amine group where the methyl-amine distance is approximately 3 Å, while simultaneously adopting two equally probable conformations relative to the carbonyl group, corresponding to distances close to 3 and 4 Å. Fluorinating this methyl group progressively increases the probability of visiting a conformation that is both farther from the amine group and closer to the carbonyl, in agreement with the decrease in the number of carbonyl-water hydrogen bonds and the increase in amine-water hydrogen bonds observed for this series of amino acids (SI Table ).