QM/MM study of the binding of H₂ to MoCu CO dehydrogenase: development and applications of improved H₂ van der Waals parameters

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.