While our simulations are unable to elucidate the role of the new conformers observed by MD simulations for W185 in IsPETase and of the equivalent tryptophan residue in all variants of BurPL, TfCut, and LCC, recent works have provided valuable insights. Plastic degradation assays and molecular dynamics simulations by Guo et al. showed that PET polymers can bind in two different backbone conformations on the active site of IsPETase, trans (straight polymer conformation) and gauche (twisted polymer conformation), with a preferential selectivity for the gauche conformation that is abundant in PET films but absent in pretreated PET bottles. Interestingly, they design a trans-selective mutant (S238A) that has higher binding affinity to PET films than the wild-type enzyme and 3-fold higher activity against an all-trans PET substrates, which is enabled by W185 adopting conformer A to enable polymer binding in trans. In addition, a similar work on computational and experimental engineering of IsPETase to enhance its activity against PET shows that W185 in the wild-type enzyme adopts conformers different from B to establish parallel displaced interactions with the terephthalic ring in the lowest-energy, catalytically competent predicted pose. Conversely, the W159H/S238F mutant, with higher activity against PET, binds the substrate in a conformer similar to B to establish T-shaped interactions. Moreover, when modeling the binding of polyethylene-2,5furandicarboxylate (PEF), an emerging bioplastic for replacing PET that is also degraded by IsPETase, W185 adopts conformers similar to D and A in the wild-type and W159H/S238F mutant enzymes, respectively.