{"id":{"repo_id":"uwo","oai_identifier":"oai:uwo.scholaris.ca:20.500.14721/28879"},"canonical_url":"https://search.dev.ndltd.org/etd/uwo/oai:uwo.scholaris.ca:20.500.14721/28879","repository":{"repo_id":"uwo","name":"Western University","base_url":"https://uwo.scholaris.ca/server/oai/request"},"display":{"title":"Investigating the Rotary Mechanism of ATP Synthase Using Molecular Dynamics Simulations","abstract":"F1-ATPase is a motor protein that can use ATP hydrolysis to drive rotation of the central subunit. The γ C-terminal helix constitutes of the rotor tip that is seated in an apical bearing formed by the α3β3 head. It remains uncertain to what extent the γ conformation during rotation differs from that seen in rigid crystal structures. Existing models assume that the entire γ subunit participates in every rotation. Here we develop a molecular dynamics (MD) strategy to model the off-axis forces acting on γ in F1-ATPase. MD runs showed stalling of the rotor tip and unfolding of the γ C-terminal helix. MD-predicted H-bond opening events coincided with experimental HDX patterns obtained in our laboratory. HDX-MS data suggests that in vitro operation of F1-ATPase is associated with significant rotational resistance in the apical bearing. These conditions cause the γ C-terminal helix to get “stuck” while the remainder of γ continues to rotate. This scenario contrasts the traditional “greasy bearing” model that envisions smooth rotation of the γ C-terminal helix. Our work also demonstrates that MD simulations can provide insights into protein dynamic features that are invisible in static X-ray crystal structures.","abstract_html":"F1-ATPase is a motor protein that can use ATP hydrolysis to drive rotation of the central subunit. The γ C-terminal helix constitutes of the rotor tip that is seated in an apical bearing formed by the α3β3 head. It remains uncertain to what extent the γ conformation during rotation differs from that seen in rigid crystal structures. Existing models assume that the entire γ subunit participates in every rotation. Here we develop a molecular dynamics (MD) strategy to model the off-axis forces acting on γ in F1-ATPase. MD runs showed stalling of the rotor tip and unfolding of the γ C-terminal helix. MD-predicted H-bond opening events coincided with experimental HDX patterns obtained in our laboratory. HDX-MS data suggests that in vitro operation of F1-ATPase is associated with significant rotational resistance in the apical bearing. These conditions cause the γ C-terminal helix to get “stuck” while the remainder of γ continues to rotate. This scenario contrasts the traditional “greasy bearing” model that envisions smooth rotation of the γ C-terminal helix. Our work also demonstrates that MD simulations can provide insights into protein dynamic features that are invisible in static X-ray crystal structures.","abstract_has_math":false,"creators":["Murcia Rios, Angela Marcela"],"institution":"The University of Western Ontario","degree_name":"M Sc","degree_level":null,"degree_discipline":"Chemistry","degree_department":null,"school":null,"contributors":[],"advisors":["Konermann, Lars"],"committee_chairs":[],"committee_members":[],"year":2019,"date_issued":"2019-04-24","date_published":"2019-04-24","updated_at":"2026-07-27T21:56:11Z","subjects":["ATP Synthase","ATP Hydrolysis","Molecular Dynamics Simulation","Mass Spectrometry","Hydrogen Deuterium Exchange"],"languages":["en_ca"],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://hdl.handle.net/20.500.14721/28879","outbound_label":"Handle","outbound_source":"dc:identifier.uri"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.advisor","label":"Advisor","values":["Konermann, Lars"]},{"key":"dc:creator","label":"Author","values":["Murcia Rios, Angela Marcela"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.accessioned","label":"Dc Date Accessioned","values":["2025-07-10T16:16:01Z"]},{"key":"dc:date.available","label":"Dc Date Available","values":["2025-07-10T16:16:01Z"]},{"key":"dc:date.issued","label":"Date","values":["2019-04-24"]},{"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":["Chemistry"]},{"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":["ATP Synthase","ATP Hydrolysis","Molecular Dynamics Simulation","Mass Spectrometry","Hydrogen Deuterium Exchange"]}]},{"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/20.500.14721/28879"]}]},{"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":["F1-ATPase is a motor protein that can use ATP hydrolysis to drive rotation of the central subunit. The γ C-terminal helix constitutes of the rotor tip that is seated in an apical bearing formed by the α3β3 head. It remains uncertain to what extent the γ conformation during rotation differs from that seen in rigid crystal structures. Existing models assume that the entire γ subunit participates in every rotation. Here we develop a molecular dynamics (MD) strategy to model the off-axis forces acting on γ in F1-ATPase. MD runs showed stalling of the rotor tip and unfolding of the γ C-terminal helix. MD-predicted H-bond opening events coincided with experimental HDX patterns obtained in our laboratory. HDX-MS data suggests that in vitro operation of F1-ATPase is associated with significant rotational resistance in the apical bearing. These conditions cause the γ C-terminal helix to get “stuck” while the remainder of γ continues to rotate. This scenario contrasts the traditional “greasy bearing” model that envisions smooth rotation of the γ C-terminal helix. Our work also demonstrates that MD simulations can provide insights into protein dynamic features that are invisible in static X-ray crystal structures."]},{"key":"dc:title","label":"Title","values":["Investigating the Rotary Mechanism of ATP Synthase Using Molecular Dynamics Simulations"]}]}],"canonical_facts":{"dc:contributor.advisor":["Konermann, Lars"],"dc:creator":["Murcia Rios, Angela Marcela"],"dc:date.accessioned":["2025-07-10T16:16:01Z"],"dc:date.available":["2025-07-10T16:16:01Z"],"dc:date.issued":["2019-04-24"],"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":["F1-ATPase is a motor protein that can use ATP hydrolysis to drive rotation of the central subunit. The γ C-terminal helix constitutes of the rotor tip that is seated in an apical bearing formed by the α3β3 head. It remains uncertain to what extent the γ conformation during rotation differs from that seen in rigid crystal structures. Existing models assume that the entire γ subunit participates in every rotation. Here we develop a molecular dynamics (MD) strategy to model the off-axis forces acting on γ in F1-ATPase. MD runs showed stalling of the rotor tip and unfolding of the γ C-terminal helix. MD-predicted H-bond opening events coincided with experimental HDX patterns obtained in our laboratory. HDX-MS data suggests that in vitro operation of F1-ATPase is associated with significant rotational resistance in the apical bearing. These conditions cause the γ C-terminal helix to get “stuck” while the remainder of γ continues to rotate. This scenario contrasts the traditional “greasy bearing” model that envisions smooth rotation of the γ C-terminal helix. Our work also demonstrates that MD simulations can provide insights into protein dynamic features that are invisible in static X-ray crystal structures."],"dc:identifier.uri":["https://hdl.handle.net/20.500.14721/28879"],"dc:language.iso":["en_ca"],"dc:publisher":["The University of Western Ontario"],"dc:subject":["ATP Synthase","ATP Hydrolysis","Molecular Dynamics Simulation","Mass Spectrometry","Hydrogen Deuterium Exchange"],"dc:title":["Investigating the Rotary Mechanism of ATP Synthase Using Molecular Dynamics Simulations"],"dc:type":["thesis"],"thesis:degree_discipline":["Chemistry"],"thesis:degree_name":["M Sc"]},"updated_at":"2026-07-27T21:56:11Z"}