BPS2026 – Force field development and quantum approaches to copper-mediated biological methane oxidation

Membrane-bound proteins play essential roles in biological redox chemistry, often leveraging transition metals to catalyze challenging transformations. One such system is particulate methane monooxygenase (pMMO), a copper-dependent enzyme that oxidizes methane under ambient conditions. Despite its biochemical relevance, dynamics of the protein environment and mechanistic details of C-H activation in pMMO remain unclear. To enable molecular dynamic (MD) simulations, we have developed bonded models for Bis-His, Cu B , and Cu D sites in pMMO that reflect the native coordination geometry. While MD provides insight into overall protein structure and dynamics, QM methods are needed to probe active site chemistry. Transition metal systems pose challenges due to electron exchange and correlation effects. We have also benchmarked QM methods against experimental data from mimetic copper-containing systems. By integrating MD and QM approaches, our work seeks to provide accurate and reliable methods to characterize the mechanism of methane oxidation in pMMO.