{"id":{"repo_id":"lethbridge","oai_identifier":"oai:opus.uleth.ca:10133/1292"},"canonical_url":"https://search.dev.ndltd.org/etd/lethbridge/oai:opus.uleth.ca:10133/1292","repository":{"repo_id":"lethbridge","name":"University of Lethbridge","base_url":"https://opus.uleth.ca/server/oai/request"},"display":{"title":"Computational modeling of the hydrolysis of 2'-deoxyribonucleic acids","abstract":"The mechanism for the hydrolysis of 2′-deoxyribonucleosides is examined using computational chemistry techniques. Initially, a model capable of accurately predicting the mechanism and activation barrier for the uncatalyzed hydrolysis of 2′-deoxyuridine is designed. It is found that the smallest model includes both explicit and implicit solvation during the optimization step. Next, this hybrid solvation model is applied to four natural nucleosides, namely 2′-deoxyadenosine, 2′-deoxycytidine, 2′-deoxyguanosine and thymidine. The hybrid model correctly predicts the trend in activation Gibbs energies for the pyrimidines and purines, separately. Finally, the concepts developed during the generation of the uncatalyzed hydrolysis model are applied to the mechanism of action of a glycosylase enzyme, namely human uracil DNA glycosylase. A hybrid ONIOM approach is utilized to study the experimentally proposed two-step mechanism. Results regarding the protonation state of His148 are inconclusive, and future directions are proposed.","abstract_html":"The mechanism for the hydrolysis of 2′-deoxyribonucleosides is examined using computational chemistry techniques. Initially, a model capable of accurately predicting the mechanism and activation barrier for the uncatalyzed hydrolysis of 2′-deoxyuridine is designed. It is found that the smallest model includes both explicit and implicit solvation during the optimization step. Next, this hybrid solvation model is applied to four natural nucleosides, namely 2′-deoxyadenosine, 2′-deoxycytidine, 2′-deoxyguanosine and thymidine. The hybrid model correctly predicts the trend in activation Gibbs energies for the pyrimidines and purines, separately. Finally, the concepts developed during the generation of the uncatalyzed hydrolysis model are applied to the mechanism of action of a glycosylase enzyme, namely human uracil DNA glycosylase. A hybrid ONIOM approach is utilized to study the experimentally proposed two-step mechanism. Results regarding the protonation state of His148 are inconclusive, and future directions are proposed.","abstract_has_math":false,"creators":["Przybylski, Jennifer L.","University of Lethbridge. Faculty of Arts and Science"],"institution":null,"degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":[],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2009,"date_issued":"2009","date_published":"2009","updated_at":"2026-07-27T20:02:41Z","subjects":["Deoxyribonucleotides -- Synthesis","Hydrolysis","Chemical engineering","DNA","Dissertations, Academic"],"languages":[],"rights":[],"rights_urls":[],"identifier_entries":[{"key":"dc:identifier","label":"Identifier","values":["hdl:10133/1292"],"render_values":[{"text":"hdl:10133/1292","href":null,"code":true}]}]},"links":{"outbound_url":null,"outbound_label":null,"outbound_source":null},"metadata_groups":[{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.issued","label":"Date","values":["2009"]},{"key":"dc:type","label":"Dc Type","values":["Thesis"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Deoxyribonucleotides -- Synthesis","Hydrolysis","Chemical engineering","DNA","Dissertations, Academic"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["hdl:10133/1292"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.other","label":"Dc Description Other","values":["The mechanism for the hydrolysis of 2′-deoxyribonucleosides is examined using computational chemistry techniques. Initially, a model capable of accurately predicting the mechanism and activation barrier for the uncatalyzed hydrolysis of 2′-deoxyuridine is designed. It is found that the smallest model includes both explicit and implicit solvation during the optimization step. Next, this hybrid solvation model is applied to four natural nucleosides, namely 2′-deoxyadenosine, 2′-deoxycytidine, 2′-deoxyguanosine and thymidine. The hybrid model correctly predicts the trend in activation Gibbs energies for the pyrimidines and purines, separately. Finally, the concepts developed during the generation of the uncatalyzed hydrolysis model are applied to the mechanism of action of a glycosylase enzyme, namely human uracil DNA glycosylase. A hybrid ONIOM approach is utilized to study the experimentally proposed two-step mechanism. Results regarding the protonation state of His148 are inconclusive, and future directions are proposed."]},{"key":"dc:title","label":"Title","values":["Computational modeling of the hydrolysis of 2'-deoxyribonucleic acids"]}]}],"canonical_facts":{"dc:date.issued":["2009"],"dc:description.other":["The mechanism for the hydrolysis of 2′-deoxyribonucleosides is examined using computational chemistry techniques. Initially, a model capable of accurately predicting the mechanism and activation barrier for the uncatalyzed hydrolysis of 2′-deoxyuridine is designed. It is found that the smallest model includes both explicit and implicit solvation during the optimization step. Next, this hybrid solvation model is applied to four natural nucleosides, namely 2′-deoxyadenosine, 2′-deoxycytidine, 2′-deoxyguanosine and thymidine. The hybrid model correctly predicts the trend in activation Gibbs energies for the pyrimidines and purines, separately. Finally, the concepts developed during the generation of the uncatalyzed hydrolysis model are applied to the mechanism of action of a glycosylase enzyme, namely human uracil DNA glycosylase. A hybrid ONIOM approach is utilized to study the experimentally proposed two-step mechanism. Results regarding the protonation state of His148 are inconclusive, and future directions are proposed."],"dc:identifier":["hdl:10133/1292"],"dc:subject":["Deoxyribonucleotides -- Synthesis","Hydrolysis","Chemical engineering","DNA","Dissertations, Academic"],"dc:title":["Computational modeling of the hydrolysis of 2'-deoxyribonucleic acids"],"dc:type":["Thesis"]},"updated_at":"2026-07-27T20:02:41Z"}