{"id":{"repo_id":"uwo","oai_identifier":"oai:uwo.scholaris.ca:20.500.14721/31756"},"canonical_url":"https://search.dev.ndltd.org/etd/uwo/oai:uwo.scholaris.ca:20.500.14721/31756","repository":{"repo_id":"uwo","name":"Western University","base_url":"https://uwo.scholaris.ca/server/oai/request"},"display":{"title":"Elucidating the Structural and Dynamical Properties of the Intrinsically Disordered Protein Nrf2 Using Molecular Dynamics Simulations","abstract":"The nuclear factor erythroid 2-related factor 2 (Nrf2) protein is a critical transcription factor for activating the antioxidant response pathway, a primary defense mechanism against disproportionate levels of oxidants in the cell, via the upregulation of cytoprotective genes. Notably, aberrant activation of Nrf2 in cancer cells increases their resistance to chemotherapy, rendering the treatment ineffective. The focus was to uncover the conformational landscape of Nrf2’s Neh4 and Neh5 domains, which participate in crucial interactions for complete transcriptional activation. Since Nrf2 is an intrinsically disordered protein (IDP), molecular dynamics simulations were employed to capture its dynamic nature and conformational heterogeneity. The Neh4 and Neh5 domains differed in their structural propensities, where the phosphorylation of Neh5’s S193 residue had little effect. This work points to the domains having potentially different binding mechanisms. In addition, performance discrepancies between force fields CHARMM36m and Amber99SB*-ILDNP were identified, potentially contributing to future force field development.","abstract_html":"The nuclear factor erythroid 2-related factor 2 (Nrf2) protein is a critical transcription factor for activating the antioxidant response pathway, a primary defense mechanism against disproportionate levels of oxidants in the cell, via the upregulation of cytoprotective genes. Notably, aberrant activation of Nrf2 in cancer cells increases their resistance to chemotherapy, rendering the treatment ineffective. The focus was to uncover the conformational landscape of Nrf2’s Neh4 and Neh5 domains, which participate in crucial interactions for complete transcriptional activation. Since Nrf2 is an intrinsically disordered protein (IDP), molecular dynamics simulations were employed to capture its dynamic nature and conformational heterogeneity. The Neh4 and Neh5 domains differed in their structural propensities, where the phosphorylation of Neh5’s S193 residue had little effect. This work points to the domains having potentially different binding mechanisms. In addition, performance discrepancies between force fields CHARMM36m and Amber99SB*-ILDNP were identified, potentially contributing to future force field development.","abstract_has_math":false,"creators":["Chang, Megan Nicole"],"institution":"The University of Western Ontario","degree_name":"M Sc","degree_level":null,"degree_discipline":"Biochemistry","degree_department":null,"school":null,"contributors":[],"advisors":["Choy, Wing-Yiu","Karttunen, Mikko"],"committee_chairs":[],"committee_members":[],"year":2021,"date_issued":"2021-12-14","date_published":"2021-12-14","updated_at":"2026-07-27T21:56:14Z","subjects":["conformational landscape","molecular dynamics simulations","force fields","coupled folding and binding","antioxidant response","phosphorylation"],"languages":["en_ca"],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://hdl.handle.net/20.500.14721/31756","outbound_label":"Handle","outbound_source":"dc:identifier.uri"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.advisor","label":"Advisor","values":["Choy, Wing-Yiu","Karttunen, Mikko"]},{"key":"dc:creator","label":"Author","values":["Chang, Megan Nicole"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.accessioned","label":"Dc Date Accessioned","values":["2025-07-10T19:22:00Z"]},{"key":"dc:date.available","label":"Dc Date Available","values":["2025-07-10T19:22:00Z"]},{"key":"dc:date.issued","label":"Date","values":["2021-12-14"]},{"key":"dc:publisher","label":"Institution","values":["The University of Western Ontario"]},{"key":"dc:type","label":"Dc Type","values":["thesis"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Biochemistry"]},{"key":"thesis:degree_name","label":"Degree Name","values":["M Sc"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["conformational landscape","molecular dynamics simulations","force fields","coupled folding and binding","antioxidant response","phosphorylation"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language.iso","label":"Language (ISO)","values":["en_ca"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.uri","label":"Identifier URI","values":["https://hdl.handle.net/20.500.14721/31756"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["The thesis cover page in the PDF document includes references to Western University’s previous institutional repository platform, known as Scholarship@Western, and links to that platform (beginning with ir.lib.uwo.ca). In citing or referring to this thesis, use the DOI or handle from this page instead. Sample citation: Author name, \"Thesis title.\" (Year). Western University Open Repository. https://doi.org/10.71858/123456."]},{"key":"dc:description.abstract","label":"Abstract","values":["The nuclear factor erythroid 2-related factor 2 (Nrf2) protein is a critical transcription factor for activating the antioxidant response pathway, a primary defense mechanism against disproportionate levels of oxidants in the cell, via the upregulation of cytoprotective genes. Notably, aberrant activation of Nrf2 in cancer cells increases their resistance to chemotherapy, rendering the treatment ineffective. The focus was to uncover the conformational landscape of Nrf2’s Neh4 and Neh5 domains, which participate in crucial interactions for complete transcriptional activation. Since Nrf2 is an intrinsically disordered protein (IDP), molecular dynamics simulations were employed to capture its dynamic nature and conformational heterogeneity. The Neh4 and Neh5 domains differed in their structural propensities, where the phosphorylation of Neh5’s S193 residue had little effect. This work points to the domains having potentially different binding mechanisms. In addition, performance discrepancies between force fields CHARMM36m and Amber99SB*-ILDNP were identified, potentially contributing to future force field development."]},{"key":"dc:title","label":"Title","values":["Elucidating the Structural and Dynamical Properties of the Intrinsically Disordered Protein Nrf2 Using Molecular Dynamics Simulations"]}]}],"canonical_facts":{"dc:contributor.advisor":["Choy, Wing-Yiu","Karttunen, Mikko"],"dc:creator":["Chang, Megan Nicole"],"dc:date.accessioned":["2025-07-10T19:22:00Z"],"dc:date.available":["2025-07-10T19:22:00Z"],"dc:date.issued":["2021-12-14"],"dc:description":["The thesis cover page in the PDF document includes references to Western University’s previous institutional repository platform, known as Scholarship@Western, and links to that platform (beginning with ir.lib.uwo.ca). In citing or referring to this thesis, use the DOI or handle from this page instead. Sample citation: Author name, \"Thesis title.\" (Year). Western University Open Repository. https://doi.org/10.71858/123456."],"dc:description.abstract":["The nuclear factor erythroid 2-related factor 2 (Nrf2) protein is a critical transcription factor for activating the antioxidant response pathway, a primary defense mechanism against disproportionate levels of oxidants in the cell, via the upregulation of cytoprotective genes. Notably, aberrant activation of Nrf2 in cancer cells increases their resistance to chemotherapy, rendering the treatment ineffective. The focus was to uncover the conformational landscape of Nrf2’s Neh4 and Neh5 domains, which participate in crucial interactions for complete transcriptional activation. Since Nrf2 is an intrinsically disordered protein (IDP), molecular dynamics simulations were employed to capture its dynamic nature and conformational heterogeneity. The Neh4 and Neh5 domains differed in their structural propensities, where the phosphorylation of Neh5’s S193 residue had little effect. This work points to the domains having potentially different binding mechanisms. In addition, performance discrepancies between force fields CHARMM36m and Amber99SB*-ILDNP were identified, potentially contributing to future force field development."],"dc:identifier.uri":["https://hdl.handle.net/20.500.14721/31756"],"dc:language.iso":["en_ca"],"dc:publisher":["The University of Western Ontario"],"dc:subject":["conformational landscape","molecular dynamics simulations","force fields","coupled folding and binding","antioxidant response","phosphorylation"],"dc:title":["Elucidating the Structural and Dynamical Properties of the Intrinsically Disordered Protein Nrf2 Using Molecular Dynamics Simulations"],"dc:type":["thesis"],"thesis:degree_discipline":["Biochemistry"],"thesis:degree_name":["M Sc"]},"updated_at":"2026-07-27T21:56:14Z"}