Relative energies of two different acid forms, analogous to the 1KDI structures in Fig. and Fig. , are listed in Table with a sign convention such that the imidazolium-flipped form is more stable when ∆E < 0. These calculations, performed at the B3LYP+D3(BJ)/ 6-31+G* level, suggest that the flipped form is preferred for the enzymes 1E5Y, 1ID2, and 2CAK, as it emerges lower in energy regardless of the boundary conditions. For the other two examples (1KDI and 1PZA), it is unclear which form is preferred because different boundary conditions afford different relative energies.