In some cases, initial geometry optimizations resulted in hydrogen bonding between the amino acid side chain and backbone to different extent in radical and non-radical structures. This intramolecular hydrogen bonding is well known, and has also been found in a comprehensive study of the conformational landscape of amino acid dipeptides. For the computation of BDEs, this would lead to energetic artifacts. Intramolecular hydrogen bonding is unlikely to occur in proteins, since the backbone amide groups are involved in secondary structure formation. In aqueous solution, polar side chain groups will also be hydrogen-bonded to water molecules or coordinated to metal ions. Therefore, we aimed at minimizing intramolecular hydrogen bonding and changes in hydrogen bonding pattern. To this end, the same initial structure was used for geometry optimizations of both dipeptides and dipeptide radicals to reflect the potential structural constraints imposed by the protein that would make large conformational changes unlikely. Further efforts to this end are described in the SI. Yet, in some cases, significant changes in hydrogen bonding strength or pattern were observed, as specified in further detail in Table .