biostudies-literatureNassir SUniversit? Mohammed VI PolytechniqueFunda??o para a Ci?ncia e a TecnologiaNovo Nordisk Fonden2284-2298https://www.ebi.ac.uk/biostudies/studies/S-EPMC12933714biostudies-literatureUnknown66(4)Polyethylene terephthalate (PET) is a widely used plastic due to its durability and adaptability; however, its resistance to natural degradation has led to severe accumulation in the environment. Recently, a PET-degrading marine bacterium, <i>Pseudomonas aestusnigri</i>, was identified and proposed for possible use in sustainable plastic recycling, particularly the PE-H enzyme, which hydrolyses PET with MHET as the main hydrolysis product. In this work, we investigate the reaction mechanism of PE-H through umbrella sampling hybrid quantum mechanics/molecular mechanics molecular dynamics simulations at the PBE/AMBER level. Our results show a two-stage reaction pathway: acylation and deacylation, both of which proceed stepwise via tetrahedral intermediate formation. We identified deacylationJournal of chemical information and modelingMechanism of Polyester Hydrolysis by Marine Bacterium PE-H Enzyme: an Atomistic and Thermodynamic Characterization.PMC129337142021.00391.CEECIND/CP1662/CT0003UIDP/50006/2020LA/P/0008/2020UIDB/50006/2020NNF22OC0072891Neves RPPNassir SPaiva PRamos MJFernandes PAEl Allali AfalseMechanism of Polyester Hydrolysis by Marine Bacterium PE-H Enzyme: an Atomistic and Thermodynamic Characterization.Polyethylene terephthalate (PET) is a widely used plastic due to its durability and adaptability; however, its resistance to natural degradation has led to severe accumulation in the environment. Recently, a PET-degrading marine bacterium, <i>Pseudomonas aestusnigri</i>, was identified and proposed for possible use in sustainable plastic recycling, particularly the PE-H enzyme, which hydrolyses PET with MHET as the main hydrolysis product. In this work, we investigate the reaction mechanism of PE-H through umbrella sampling hybrid quantum mechanics/molecular mechanics molecular dynamics simulations at the PBE/AMBER level. Our results show a two-stage reaction pathway: acylation and deacylation, both of which proceed stepwise via tetrahedral intermediate formation. We identified deacylation2026-01-01T00:00:00Z2026 Feb2026-07-16T21:32:30.112Z2026-07-10T03:16:21.184ZS-EPMC129337144167721010.1021/acs.jcim.5c02314