The MoCu CO dehydrogenase enzyme not only transforms CO into CO2 but it can also oxidise H2. Even if its hydrogenase activity has been known for decades, a debate is ongoing on the most plausible mode for the binding of H2 to the enzyme active site and the hydrogen oxidation mechanism. In the present work, we provide a new perspective on the MoCu-CODH hydrogenase activity by improving the in silico description of the enzyme. Energy refinement-by means of the BigQM approach-was performed on the intermediates involved in the dihydrogen oxidation catalysis reported in our previously published work (Rovaletti, et al. "Theoretical Insights into the Aerobic Hydrogenase Activity of Molybdenum-Copper CO Dehydrogenase." Inorganics 7 (2019) 135). A suboptimal description of the H2-HN(backbone) interaction was observed when the van der Waals parameters described in previous literature for H2 were employed. Therefore, a new set of van der Waals parameters is developed here in order to better describe the hydrogen-backbone interaction. They give rise to improved binding modes of H2 in the active site of MoCu CO dehydrogenase. Implications of the resulting outcomes for a better understanding of hydrogen oxidation catalysis mechanisms are proposed and discussed.
Keywords: BigQM approach; Force field parametrization; H2 oxidation; Hydrogenases; MoCu CO dehydrogenase; QM/MM.