Computational Insights into the Catalytic Mechanism of Is‐PETase: An Enzyme Capable of Degrading Poly(ethylene) Terephthalate

Is‐PETase has become an enzyme of significant interest due to its ability to catalyse the degradation of polyethylene terephthalate (PET) at mesophilic temperatures. We performed hybrid quantum mechanics and molecular mechanics (QM/MM) at the DSD‐PBEP86‐D3/ma‐def2‐TZVP/CHARMM27//rev‐PBE‐D3/dev2‐SVP/CHARMM level to calculate the energy profile for the degradation of a suitable PET model by this enzyme. Very low overall barriers are computed for serine protease‐type hydrolysis steps (as low as 34.1 kJ mol(−1)). Spontaneous deprotonation of the final product, terephthalic acid, with a high computed driving force indicates that product release could be rate limiting.