The main hyperparameter for the combinatorial graph enumeration is the maximum number of bonds broken or formed. Other works have suggested setting this number to two. However, by only allowing two bonds to be formed or broken, we do not find Reaction 2 (Figure , which not only has the second-lowest barrier but is also the thermodynamic product. If we instead allow all the molecules to form and break three bonds but constrain the total number of changes to five, we find 74 of the 75 products that Grambow et al. found. The missing reaction (R62 in Table ) has more than five bonds broken and formed and the barrier is 80 kcal/mol. This approach results in a total of 27,577 unique reactions involving 4,095 unique fragments, for which we perform a systematic conformational search. For many of the reactions, none of the conformers successfully converged with PM3 while for other reactions, the atom connectivity changed during the optimizations and were therefore discarded. Thus, only 1,138 of the fragments calculations resulted in a fragment energy allowing us to compute reaction energies for 9,056 of the 27,577 reactions. As seen in the distribution of reaction energies in Figure most of the reactions have high reaction energies.