OPTIMIZING PET BIORECYCLING SOLUTIONS THROUGH ELECTRONICALLY POLARIZABLE SIMULATIONS

Polyethylene terephthalate (PET) is one of the most abundantly produced plastics and about three-quarters of the annual production becomes waste, leading to significant plastic accumulation and a global environmental and health crisis. PET hydrolases represent a potential solution and a novel biorecycling technology by enabling PET production at a cost similar to that of industrial-scale virgin PET synthesis. Still, enzyme activity on crystalline PET and in low-pH media must be improved to meet this goal. Here, we used polarizable molecular dynamics
simulations with the Drude force field and developed a parameter set to model PET polymers to characterize the electronic properties of PET-protein interfaces. First, we simulated the PET hydrolase from Ideonella sakaiensis (IsPETase) bound to bis(2-hydroxyethyl) terephthalate (BHET) and characterized the electronic plasticity of the substrate. We found that IsPETase exerts a strong electric field at the substrate carbonyl carbon atom, which is the acylation reaction electrophile. Also, we observed a strong electric field of ~110 MV/cm exerted along the C=O bond that should stabilize the acylated intermediate and lower the reaction activation barrier. Enhancing these features could help optimize PET hydrolases to low-pH conditions. Moreover, we investigated the reported enhancement of PET hydrolase activity through their fusion to carbohydrate binding modules (CBM). We simulated the interaction of a chitin-binding module (PDB 1HEV) and a PET crystal lattice. We observed the Drude force field yields an interaction energy ~20 kcal/mol stronger than with CHARMM36m. We correlated this difference to the polarization response of the PET lattice outer layers in the Drude simulations. Together, our results characterizing electric fields driving PET hydrolase catalysis and the interaction between PET crystals and CBMs revealed promising design possibilities that could further improve PET hydrolase technology and its utility in biorecycling.
 

This work was supported by the National Institutes of Health (grant R35GM133754 to J.A.L.), and the U.S. Department of Agriculture National Institute of Food and Agriculture (project number VA-160092 to J.A.L.).