In the apoenzyme, the situation is seemingly reversed than in the case of the E:S and E:P complexes. Our calculations indicate a preference for H transfer to the si over the re face of the glycyl radical (barriers of 80.6 kJ/mol vs 107 kJ/mol), which would indicate an almost 40,000 faster rate of S-GlyDH formation (Table ). However, we have to remember that those barriers are calculated with respect to the E apo conformational states, which were derived from an internal reaction coordinate scan started at the si or re-oriented TS apo . As a result, the conformational changes enforced during the optimization of the TS may persist at the E apo or I apo states. It turned out that the energy of the proS conformer of E apo is 86.8 kJ/mol higher than that of the proR conformer. Such a situation was not observed in the case of the E:S and E:P models where the energy differences between the respective reference states were minimal.