Transforming Computational Power into Environmental Solutions: HPC-driven Research on Urethanase-mediated Plastic Degradation

The extensive accumulation of persistent synthetic polymers has made plastics a rapidly expanding global concern. In this context, enzymatic degradation offers a viable and environmentally friendly alternative to the conventional plastic recycling methods. Here, we discuss how multi-microsecond Molecular Dynamics (MD) simulations and hybrid Quantum Mechanics/Molecular Mechanics (QM/MM) methods have allowed us to shed light on the conformational dynamics and catalytic mechanisms underlying the activity of the polyurethane-degrading enzymes UMG-SP2 and UMG-SP3. Our findings emphasize the role of these computational approaches for the identification of the rate-limiting step, stationary states’ geometries, and residue-specific electrostatic effects, enabling subsequent mutagenesis studies to enhance the efficiency of these urethanases. The access to EuroHPC’s computing resources was essential to this research, as it allowed the extensive sampling of enzyme:substrate dynamics over large simulation timescales and the QM/MM-level resolution of the free-energy profile associated with the cleavage of the substrate’s urethane bond. This work demonstrates the relevant role of HPC-driven research in advancing mechanistic insights and highlights how the synergy between large-scale computational resources and enzymatic knowledge can enhance our understanding of plastic biodegradation.