Computational Insights into the molecular dynamics of the binding of ligands in the Methanol Dehydrogenase

Methanol dehydrogenase (MDH) is a promising biocatalyst for industrial use, converting methanol to formaldehyde. Our molecular modeling revealed methanol binds to MDH with ∼7 kcal/mol free energy, while formaldehyde binds with ∼4 kcal/mol. This suggests methanol remains longer in the active site, and formaldehyde exits more readily post-reaction. These insights are crucial for designing more efficient MDH variants for industrial applications. Graphical abstract The left panel shows methanol and formaldehyde within the active site of methanol dehydrogenase, illustrating entry and release paths. The right panel presents the free energy profiles, indicating methanol’s stronger binding affinity and formaldehyde’s easier release post-reaction.