Regarding the conserved Trp, the unbiased MD simulations visited additional conformers A, D and E for the S/I PETases on a 500ns timescale. Meanwhile, the free energy surfaces emerging from thorough exploration via metadynamics shows how rotating through different basins is more likely in S/I PETases (which is true in general but it's particularly important for basins A and B), after elimination of the steric effects caused by the conserved His and Phe residues. This enhanced rotation could be important for facilitating substrate binding and product release.