{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T14:18:20Z","timestamp":1789395500067,"version":"build-2803163510"},"reference-count":44,"publisher":"American Chemical Society (ACS)","issue":"17","license":[{"start":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T00:00:00Z","timestamp":1786924800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T00:00:00Z","timestamp":1786924800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T00:00:00Z","timestamp":1786924800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-045"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["92580104"],"award-info":[{"award-number":["92580104"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/na","name":"Science and Technology Development Fund, Macau SAR","doi-asserted-by":"publisher","award":["0030\/2022\/AGJ"],"award-info":[{"award-number":["0030\/2022\/AGJ"]}],"id":[{"id":"10.13039\/na","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/na","name":"National Key Research Program of China","doi-asserted-by":"publisher","award":["2022YFA1503101"],"award-info":[{"award-number":["2022YFA1503101"]}],"id":[{"id":"10.13039\/na","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/na","name":"National Key Research Program of China","doi-asserted-by":"publisher","award":["2025YFE0121800"],"award-info":[{"award-number":["2025YFE0121800"]}],"id":[{"id":"10.13039\/na","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/na","name":"111 Project","doi-asserted-by":"publisher","award":["NA"],"award-info":[{"award-number":["NA"]}],"id":[{"id":"10.13039\/na","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/na","name":"Collaborative Innovation Center of Suzhou Nano Science & Technology","doi-asserted-by":"publisher","award":["NA"],"award-info":[{"award-number":["NA"]}],"id":[{"id":"10.13039\/na","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/na","name":"Joint International Research Laboratory of Carbon-Based Functional Materials and Devices","doi-asserted-by":"publisher","award":["NA"],"award-info":[{"award-number":["NA"]}],"id":[{"id":"10.13039\/na","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/na","name":"Suzhou Science and Technology Development Project ? i Basic research in medical applications","doi-asserted-by":"publisher","award":["SKY2023040"],"award-info":[{"award-number":["SKY2023040"]}],"id":[{"id":"10.13039\/na","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,9,14]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Polyethylene terephthalate (PET) hydrolase-based biodegradation offers a promising route for plastic waste remediation, yet the dynamic origins of high activity and their linkage across catalytic stages still require further elucidation. Here, we focus on the Leaf-Branch Compost Cutinase (LCC) system to reveal the possible mechanistic origins underlying the elevated activity of the LCC variants. By integrating molecular dynamics simulations, enhanced sampling, and deep learning-assisted network analysis, we systematically investigate the critical prereactive stage of amorphous PET adsorption and substrate binding. We identify three mechanistic origins underlying the high activity of LCC-LANL in the prereactive state and clarify its structure\u2013dynamics\u2013function relationship: (i) enhanced interaction strength coupled with an active-pocket orientation that, despite not directly facing the amorphous PET surface, maintains closer proximity to it than LCC-WT, thus promoting substrate recruitment; (ii) higher occupancy of the PET ester bond near the catalytic triad, which forms the basis for catalysis, coupled with the efficient dynamic interchange between the \u201cW\u201d and coiled conformations near the catalytic triad; and (iii) the enhancement of prereactive organization through long-range allosteric communication by distal mutations in LCC-LANL. Additionally, we propose a region-specific cooperative optimization strategy tailored to domain-specific functional roles and distill six design principles for efficient PETases. In summary, this work elucidates the prereactive origins underlying the high activity of LCC-LANL, paving the way for future studies on actual catalytic PET hydrolysis.<\/jats:p>","DOI":"10.1021\/acs.jcim.6c01736","type":"journal-article","created":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T21:02:08Z","timestamp":1787000528000},"page":"11289-11304","source":"Crossref","is-referenced-by-count":0,"title":["Mechanistic Origins\nof Enhanced PET Hydrolase Activity\nfrom Molecular Dynamics and Deep Learning-Assisted Network Analysis"],"prefix":"10.1021","volume":"66","author":[{"given":"Jiawen","family":"Wang","sequence":"first","affiliation":[{"name":"Soochow University , , , ,","place":["Suzhou, Jiangsu, China, 215123"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haozhe","family":"Pan","sequence":"additional","affiliation":[{"name":"Macau University of Science and Technology , , , ,","place":["Taipa, Macau SAR, China, 999078"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4436-6392","authenticated-orcid":true,"given":"Huilong","family":"Dong","sequence":"additional","affiliation":[{"name":"Changshu Institute of Technology , , , ,","place":["Changshu, Jiangsu, China, 215500"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3177-2073","authenticated-orcid":true,"given":"Yujin","family":"Ji","sequence":"additional","affiliation":[{"name":"Soochow University , , , ,","place":["Suzhou, Jiangsu, China, 215123"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5248-2756","authenticated-orcid":true,"given":"Youyong","family":"Li","sequence":"additional","affiliation":[{"name":"Soochow University , , , ,","place":["Suzhou, Jiangsu, China, 215123"]},{"name":"Macau University of Science and Technology , , , ,","place":["Taipa, Macau SAR, China, 999078"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,8,17]]},"reference":[{"issue":"5462","key":"2026091409073869300_cit1","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1038\/250161a0","article-title":"Chemical and biological degradation\nof waste plastics","volume":"250","author":"Brown","year":"1974","journal-title":"Nature"},{"issue":"6","key":"2026091409073869300_cit2","doi-asserted-by":"publisher","first-page":"3382","DOI":"10.1021\/acscatal.1c05856","article-title":"Mechanism-based design of efficient pet hydrolases","volume":"12","author":"Wei","year":"2022","journal-title":"ACS Catal"},{"issue":"6278","key":"2026091409073869300_cit3","doi-asserted-by":"publisher","first-page":"1196","DOI":"10.1126\/science.aad6359","article-title":"A bacterium that degrades\nand assimilates\npoly(ethylene terephthalate)","volume":"351","author":"Yoshida","year":"2016","journal-title":"Science"},{"issue":"7802","key":"2026091409073869300_cit4","doi-asserted-by":"publisher","first-page":"216","DOI":"10.1038\/s41586-020-2149-4","article-title":"An engineered pet depolymerase\nto break down and recycle plastic bottles","volume":"580","author":"Tournier","year":"2020","journal-title":"Nature"},{"issue":"7","key":"2026091409073869300_cit5","doi-asserted-by":"publisher","first-page":"1443","DOI":"10.1002\/prot.26325","article-title":"Plastics degradation\nby hydrolytic enzymes: The plastics-active enzymes database\u2013pazy","volume":"90","author":"Buchholz","year":"2022","journal-title":"Proteins: Struct., Funct., Bioinf"},{"issue":"20","key":"2026091409073869300_cit6","doi-asserted-by":"publisher","first-page":"13156","DOI":"10.1021\/acscatal.3c02922","article-title":"Assessment of four\nengineered pet degrading enzymes considering large-scale industrial\napplications","volume":"13","author":"Arnal","year":"2023","journal-title":"ACS Catal"},{"issue":"19","key":"2026091409073869300_cit7","doi-asserted-by":"publisher","first-page":"14622","DOI":"10.1021\/acscatal.4c04321","article-title":"A high-throughput\nscreening platform for engineering\npoly(ethylene terephthalate). hydrolases","volume":"14","author":"Groseclose","year":"2024","journal-title":"ACS\nCatal"},{"issue":"33","key":"2026091409073869300_cit8","doi-asserted-by":"publisher","first-page":"30447","DOI":"10.1021\/jacs.5c10598","article-title":"The action of plastic degrading enzyme\nis accelerated\nmainly due to an increase in thermal stability rather than by an inherent\ncatalytic effect","volume":"147","author":"Nandi","year":"2025","journal-title":"J. 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Theory Comput"},{"issue":"16","key":"2026091409073869300_cit32","doi-asserted-by":"publisher","first-page":"3814","DOI":"10.1021\/acs.jcim.2c00562","article-title":"Molecular dynamics simulations of adsorption of sars-cov-2\nspike protein on polystyrene surface","volume":"62","author":"Sahihi","year":"2022","journal-title":"J. Chem.\nInf. Model"},{"issue":"11","key":"2026091409073869300_cit33","doi-asserted-by":"publisher","first-page":"5596","DOI":"10.1021\/acs.jctc.6b00701","article-title":"Multiple staggered\nmesh ewald: Boosting the accuracy\nof the smooth particle mesh ewald method","volume":"12","author":"Wang","year":"2016","journal-title":"J.\nChem. Theory Comput"},{"issue":"6","key":"2026091409073869300_cit34","doi-asserted-by":"publisher","first-page":"3559","DOI":"10.1063\/1.1590311","article-title":"Free energy calculation\nfrom steered molecular dynamics simulations using jarzynski\u2019s\nequality","volume":"119","author":"Park","year":"2003","journal-title":"J. Chem. 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