{"id":{"repo_id":"brock","oai_identifier":"oai:brocku.scholaris.ca:10464/2868"},"canonical_url":"https://search.dev.ndltd.org/etd/brock/oai:brocku.scholaris.ca:10464/2868","repository":{"repo_id":"brock","name":"Brock University","base_url":"https://brocku.scholaris.ca/server/oai/request"},"display":{"title":"Polyglutamine monomer structure and its implications for molecular self-assembly","abstract":"Polyglutamine is a naturally occurring peptide found within several proteins in neuronal cells of the brain, and its aggregation has been implicated in several neurodegenerative diseases, including Huntington's disease. The resulting aggregates have been demonstrated to possess ~-sheet structure, and aggregation has been shown to start with a single misfolded peptide. The current project sought to computationally examine the structural tendencies of three mutant poly glutamine peptides that were studied experimentally, and found to aggregate with varying efficiencies. Low-energy structures were generated for each peptide by simulated annealing, and were analyzed quantitatively by various geometry- and energy-based methods. According to the results, the experimentally-observed inhibition of aggregation appears to be due to localized conformational restraint placed on the peptide backbone by inserted prolines, which in tum confines the peptide to native coil structure, discouraging transition towards the ~sheet structure required for aggregation. Such knowledge could prove quite useful to the design of future treatments for Huntington's and other related diseases.","abstract_html":"Polyglutamine is a naturally occurring peptide found within several proteins in neuronal cells of the brain, and its aggregation has been implicated in several neurodegenerative diseases, including Huntington's disease. The resulting aggregates have been demonstrated to possess ~-sheet structure, and aggregation has been shown to start with a single misfolded peptide. The current project sought to computationally examine the structural tendencies of three mutant poly glutamine peptides that were studied experimentally, and found to aggregate with varying efficiencies. Low-energy structures were generated for each peptide by simulated annealing, and were analyzed quantitatively by various geometry- and energy-based methods. According to the results, the experimentally-observed inhibition of aggregation appears to be due to localized conformational restraint placed on the peptide backbone by inserted prolines, which in tum confines the peptide to native coil structure, discouraging transition towards the ~sheet structure required for aggregation. Such knowledge could prove quite useful to the design of future treatments for Huntington's and other related diseases.","abstract_has_math":false,"creators":["VanSchouwen, Bryan."],"institution":"Brock University","degree_name":"M.Sc. Biological Sciences","degree_level":"Masters","degree_discipline":"Faculty of Mathematics and Science","degree_department":"Department of Biological Sciences","school":null,"contributors":[],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2009,"date_issued":"2009-01-28T15:55:26Z","date_published":"2009-01-28T15:55:26Z","updated_at":"2026-07-24T01:23:14Z","subjects":["Neuropeptides.","Huntington's chorea--Treatment.","Nervous system--Degeneration--Treatment.","Nervous system -- Diseases--Treatment."],"languages":["eng"],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"http://hdl.handle.net/10464/2868","outbound_label":"Handle","outbound_source":"dc:identifier.uri"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.department","label":"Department","values":["Department of Biological Sciences"]},{"key":"dc:creator","label":"Author","values":["VanSchouwen, Bryan."]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.accessioned","label":"Dc Date Accessioned","values":["2010-01-28T15:55:26Z"]},{"key":"dc:date.available","label":"Dc Date Available","values":["2010-01-28T15:55:26Z"]},{"key":"dc:date.issued","label":"Date","values":["2009-01-28T15:55:26Z"]},{"key":"dc:type","label":"Dc Type","values":["Electronic Thesis or Dissertation"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Faculty of Mathematics and Science"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Masters"]},{"key":"thesis:degree_name","label":"Degree Name","values":["M.Sc. Biological Sciences"]},{"key":"thesis:institution_name","label":"Thesis Institution Name","values":["Brock University"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Neuropeptides.","Huntington's chorea--Treatment.","Nervous system--Degeneration--Treatment.","Nervous system -- Diseases--Treatment."]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language.iso","label":"Language (ISO)","values":["eng"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.uri","label":"Identifier URI","values":["http://hdl.handle.net/10464/2868"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["Polyglutamine is a naturally occurring peptide found within several proteins in neuronal cells of the brain, and its aggregation has been implicated in several neurodegenerative diseases, including Huntington's disease. The resulting aggregates have been demonstrated to possess ~-sheet structure, and aggregation has been shown to start with a single misfolded peptide. The current project sought to computationally examine the structural tendencies of three mutant poly glutamine peptides that were studied experimentally, and found to aggregate with varying efficiencies. Low-energy structures were generated for each peptide by simulated annealing, and were analyzed quantitatively by various geometry- and energy-based methods. According to the results, the experimentally-observed inhibition of aggregation appears to be due to localized conformational restraint placed on the peptide backbone by inserted prolines, which in tum confines the peptide to native coil structure, discouraging transition towards the ~sheet structure required for aggregation. Such knowledge could prove quite useful to the design of future treatments for Huntington's and other related diseases."]},{"key":"dc:title","label":"Title","values":["Polyglutamine monomer structure and its implications for molecular self-assembly"]}]}],"canonical_facts":{"dc:contributor.department":["Department of Biological Sciences"],"dc:creator":["VanSchouwen, Bryan."],"dc:date.accessioned":["2010-01-28T15:55:26Z"],"dc:date.available":["2010-01-28T15:55:26Z"],"dc:date.issued":["2009-01-28T15:55:26Z"],"dc:description.abstract":["Polyglutamine is a naturally occurring peptide found within several proteins in neuronal cells of the brain, and its aggregation has been implicated in several neurodegenerative diseases, including Huntington's disease. The resulting aggregates have been demonstrated to possess ~-sheet structure, and aggregation has been shown to start with a single misfolded peptide. The current project sought to computationally examine the structural tendencies of three mutant poly glutamine peptides that were studied experimentally, and found to aggregate with varying efficiencies. Low-energy structures were generated for each peptide by simulated annealing, and were analyzed quantitatively by various geometry- and energy-based methods. According to the results, the experimentally-observed inhibition of aggregation appears to be due to localized conformational restraint placed on the peptide backbone by inserted prolines, which in tum confines the peptide to native coil structure, discouraging transition towards the ~sheet structure required for aggregation. Such knowledge could prove quite useful to the design of future treatments for Huntington's and other related diseases."],"dc:identifier.uri":["http://hdl.handle.net/10464/2868"],"dc:language.iso":["eng"],"dc:subject":["Neuropeptides.","Huntington's chorea--Treatment.","Nervous system--Degeneration--Treatment.","Nervous system -- Diseases--Treatment."],"dc:title":["Polyglutamine monomer structure and its implications for molecular self-assembly"],"dc:type":["Electronic Thesis or Dissertation"],"thesis:degree_discipline":["Faculty of Mathematics and Science"],"thesis:degree_level":["Masters"],"thesis:degree_name":["M.Sc. Biological Sciences"],"thesis:institution_name":["Brock University"]},"updated_at":"2026-07-24T01:23:14Z"}