{"id":{"repo_id":"qu-belfast","oai_identifier":"oai:pure.qub.ac.uk/portal:studenttheses/89fd4336-8299-452d-9841-b3a02e80d807"},"canonical_url":"https://search.dev.ndltd.org/etd/qu-belfast/oai:pure.qub.ac.uk/portal:studenttheses/89fd4336-8299-452d-9841-b3a02e80d807","repository":{"repo_id":"qu-belfast","name":"Queen's University Belfast","base_url":"https://pureadmin.qub.ac.uk/ws/oai"},"display":{"title":"Computational study on the selectivity of iron-containing hydroxylase","abstract":"Many Iron-containing hydroxylases have a high degree of regio- and diastereoselectivity and can be used as biocatalysts for producing specific chiral alcohols from un-active C-H sites. Here C-H functionalization catalyzed by Iron-containing heme and nonheme were studied, using cytochrome P450 and PtlH as examples. In this work, the C-H activation in the hydroxylation reaction of a model substrate artemisinin catalyzed by three selective P450BM3 variants was studied by combined molecular dynamics (MD) simulations and quantum mechanics/molecular mechanics (QM/MM) calculations. A distinct linear correlation was observed between the barriers of C-H bond activation and the distances between Fe=O oxo and the hydrogen atom to be abstracted. These findings would provide valuable guidance for predicting the reactivity of P450BM3 and other similar reactions where hydrogen abstraction is the rate-limiting step. The second part of the project is the study on non-heme hydroxylase PtlH. In this section, a new descriptor ΔGCat Effi that is related to both the substrate binding affinity and activation barrier associated with the rate-limiting hydrogen abstraction step was proposed and tested. With current data, ΔGCat Effi showed promising result in explaining the selectivity in C-H activation and may be used to predict the selectivity of other iron-containing heme or non-heme enzymes.","abstract_html":"Many Iron-containing hydroxylases have a high degree of regio- and diastereoselectivity and can be used as biocatalysts for producing specific chiral alcohols from un-active C-H sites. Here C-H functionalization catalyzed by Iron-containing heme and nonheme were studied, using cytochrome P450 and PtlH as examples. In this work, the C-H activation in the hydroxylation reaction of a model substrate artemisinin catalyzed by three selective P450BM3 variants was studied by combined molecular dynamics (MD) simulations and quantum mechanics/molecular mechanics (QM/MM) calculations. A distinct linear correlation was observed between the barriers of C-H bond activation and the distances between Fe=O oxo and the hydrogen atom to be abstracted. These findings would provide valuable guidance for predicting the reactivity of P450BM3 and other similar reactions where hydrogen abstraction is the rate-limiting step. The second part of the project is the study on non-heme hydroxylase PtlH. In this section, a new descriptor ΔGCat Effi that is related to both the substrate binding affinity and activation barrier associated with the rate-limiting hydrogen abstraction step was proposed and tested. With current data, ΔGCat Effi showed promising result in explaining the selectivity in C-H activation and may be used to predict the selectivity of other iron-containing heme or non-heme enzymes.","abstract_has_math":false,"creators":["Hui, Chenggong"],"institution":"Queen's University Belfast","degree_name":"Master of Philosophy","degree_level":"Masters Thesis","degree_discipline":null,"degree_department":null,"school":null,"contributors":[],"advisors":["Huang, Meilan"],"committee_chairs":[],"committee_members":[],"year":2021,"date_issued":"2021-7","date_published":"2021-7","updated_at":"2026-07-24T03:55:51Z","subjects":["QMMM","computational chemistry","molecular dynamics","DFT","P450"],"languages":["eng"],"rights":[],"rights_urls":[],"identifier_entries":[{"key":"dc:identifier","label":"Identifier","values":["oai:pure.qub.ac.uk/portal:studenttheses/89fd4336-8299-452d-9841-b3a02e80d807"],"render_values":[{"text":"oai:pure.qub.ac.uk/portal:studenttheses/89fd4336-8299-452d-9841-b3a02e80d807","href":null,"code":true}]}]},"links":{"outbound_url":"https://pure.qub.ac.uk/en/studentTheses/89fd4336-8299-452d-9841-b3a02e80d807","outbound_label":"Repository record","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.advisor","label":"Advisor","values":["Huang, Meilan"]},{"key":"dc:creator","label":"Author","values":["Hui, Chenggong"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2021-7"]},{"key":"dc:date.issued","label":"Date","values":["2021-7"]},{"key":"dc:publisher.department","label":"Dc Publisher Department","values":["School of Chemistry and Chemical Engineering"]},{"key":"dc:publisher.institution","label":"Dc Publisher Institution","values":["Queen's University Belfast"]},{"key":"dc:relation.isreferencedby","label":"Dc Relation Isreferencedby","values":["https://pure.qub.ac.uk/en/studentTheses/89fd4336-8299-452d-9841-b3a02e80d807"]},{"key":"dc:type","label":"Dc Type","values":["Thesis"]},{"key":"dc:type.qualificationlevel","label":"Dc Type Qualificationlevel","values":["Masters Thesis"]},{"key":"dc:type.qualificationname","label":"Dc Type Qualificationname","values":["Master of Philosophy"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["QMMM","computational chemistry","molecular dynamics","DFT","P450"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["eng"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["oai:pure.qub.ac.uk/portal:studenttheses/89fd4336-8299-452d-9841-b3a02e80d807","https://pure.qub.ac.uk/en/studentTheses/89fd4336-8299-452d-9841-b3a02e80d807"]},{"key":"dc:identifier.uri","label":"Identifier URI","values":["https://pure.qub.ac.uk/files/231866188/Mphil_thesis_Chenggong_4.pdf"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["Many Iron-containing hydroxylases have a high degree of regio- and diastereoselectivity and can be used as biocatalysts for producing specific chiral alcohols from un-active C-H sites. Here C-H functionalization catalyzed by Iron-containing heme and nonheme were studied, using cytochrome P450 and PtlH as examples. In this work, the C-H activation in the hydroxylation reaction of a model substrate artemisinin catalyzed by three selective P450BM3 variants was studied by combined molecular dynamics (MD) simulations and quantum mechanics/molecular mechanics (QM/MM) calculations. A distinct linear correlation was observed between the barriers of C-H bond activation and the distances between Fe=O oxo and the hydrogen atom to be abstracted. These findings would provide valuable guidance for predicting the reactivity of P450BM3 and other similar reactions where hydrogen abstraction is the rate-limiting step. The second part of the project is the study on non-heme hydroxylase PtlH. In this section, a new descriptor ΔGCat Effi that is related to both the substrate binding affinity and activation barrier associated with the rate-limiting hydrogen abstraction step was proposed and tested. With current data, ΔGCat Effi showed promising result in explaining the selectivity in C-H activation and may be used to predict the selectivity of other iron-containing heme or non-heme enzymes."]},{"key":"dc:title","label":"Title","values":["Computational study on the selectivity of iron-containing hydroxylase"]}]}],"canonical_facts":{"dc:contributor.advisor":["Huang, Meilan"],"dc:creator":["Hui, Chenggong"],"dc:date":["2021-7"],"dc:date.issued":["2021-7"],"dc:description.abstract":["Many Iron-containing hydroxylases have a high degree of regio- and diastereoselectivity and can be used as biocatalysts for producing specific chiral alcohols from un-active C-H sites. Here C-H functionalization catalyzed by Iron-containing heme and nonheme were studied, using cytochrome P450 and PtlH as examples. In this work, the C-H activation in the hydroxylation reaction of a model substrate artemisinin catalyzed by three selective P450BM3 variants was studied by combined molecular dynamics (MD) simulations and quantum mechanics/molecular mechanics (QM/MM) calculations. A distinct linear correlation was observed between the barriers of C-H bond activation and the distances between Fe=O oxo and the hydrogen atom to be abstracted. These findings would provide valuable guidance for predicting the reactivity of P450BM3 and other similar reactions where hydrogen abstraction is the rate-limiting step. The second part of the project is the study on non-heme hydroxylase PtlH. In this section, a new descriptor ΔGCat Effi that is related to both the substrate binding affinity and activation barrier associated with the rate-limiting hydrogen abstraction step was proposed and tested. With current data, ΔGCat Effi showed promising result in explaining the selectivity in C-H activation and may be used to predict the selectivity of other iron-containing heme or non-heme enzymes."],"dc:identifier":["oai:pure.qub.ac.uk/portal:studenttheses/89fd4336-8299-452d-9841-b3a02e80d807","https://pure.qub.ac.uk/en/studentTheses/89fd4336-8299-452d-9841-b3a02e80d807"],"dc:identifier.uri":["https://pure.qub.ac.uk/files/231866188/Mphil_thesis_Chenggong_4.pdf"],"dc:language":["eng"],"dc:publisher.department":["School of Chemistry and Chemical Engineering"],"dc:publisher.institution":["Queen's University Belfast"],"dc:relation.isreferencedby":["https://pure.qub.ac.uk/en/studentTheses/89fd4336-8299-452d-9841-b3a02e80d807"],"dc:subject":["QMMM","computational chemistry","molecular dynamics","DFT","P450"],"dc:title":["Computational study on the selectivity of iron-containing hydroxylase"],"dc:type":["Thesis"],"dc:type.qualificationlevel":["Masters Thesis"],"dc:type.qualificationname":["Master of Philosophy"]},"updated_at":"2026-07-24T03:55:51Z"}