{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T13:31:52Z","timestamp":1785159112905,"version":"3.55.0"},"reference-count":74,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2025,5,21]],"date-time":"2025-05-21T00:00:00Z","timestamp":1747785600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Shenzhen Municipal Government","award":["C10120180043"],"award-info":[{"award-number":["C10120180043"]}]},{"name":"Shenzhen Municipal Government","award":["LGKCSDPT2024001"],"award-info":[{"award-number":["LGKCSDPT2024001"]}]},{"name":"Longgang District","award":["C10120180043"],"award-info":[{"award-number":["C10120180043"]}]},{"name":"Longgang District","award":["LGKCSDPT2024001"],"award-info":[{"award-number":["LGKCSDPT2024001"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>The valence bond (VB) framework is widely recognized as a powerful tool for elucidating the electronic origins of activation energy barriers in chemical reactions. We employed ab initio VB calculations to investigate the hydrogen abstraction (H-abstraction) barrier in cytochrome P450 enzymes (P450s), using a simplified model in which an oriented external electric field (OEEF) was applied to efficiently capture the electronic effects of the equatorial porphyrin and proximal thiolate ligands on the iron(IV)\u2013oxo unit in compound I (Cpd I). Methane (CH4) was used as the model substrate. The VB-calculated barrier height, evaluated with this simplified model, qualitatively reproduced the barrier predicted by density functional theory (DFT) calculations using a more complete active-site model. Additionally, by examining the weights and diagonal elements of the Hamiltonian matrix for different VB structures along the reaction coordinate, we identified key VB structures\u2014including covalent and ionic configurations representing the C\u2013H and O\u2013H bonds\u2014that contribute significantly to the electronic origin of the barrier height. The mixing of these distinct VB structures leads to resonance stabilization, which is maximized at the transition state.<\/jats:p>","DOI":"10.3390\/molecules30102242","type":"journal-article","created":{"date-parts":[[2025,5,21]],"date-time":"2025-05-21T07:44:57Z","timestamp":1747813497000},"page":"2242","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Valence Bond Insights into the H-Abstraction Barrier in Cytochrome P450"],"prefix":"10.3390","volume":"30","author":[{"given":"Enhua","family":"Zhang","sequence":"first","affiliation":[{"name":"Warshel Institute for Computational Biology, School of Medicine, The Chinese University of Hong Kong, Shenzhen 518172, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hajime","family":"Hirao","sequence":"additional","affiliation":[{"name":"Warshel Institute for Computational Biology, School of Medicine, The Chinese University of Hong Kong, Shenzhen 518172, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Ortiz de Montellano, P.R. 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