We note that in some cases, the optimizations have converged in arrangements that do not match the original crystal structures from which the models were developed, and may be unfavorable for the overall mechanisms-for example, with amino acid side chains rotating away from where they will later react. While this is a problem when comparing to experimental data, here we use the same structures for both the theoretical reference values and the DFT tests, so there is less influence on the calculated deviations. The reoptimized systems should still represent the types and overall magnitude of non-covalent interactions that are seen in enzymes, even if they are configured differently, and therefore we believe that slight alterations in the structures are not harmful for the purpose of a