Computational modeling of the hydrolysis of 2'-deoxyribonucleic acids

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dc.contributor.authorPrzybylski, Jennifer L.
dc.contributor.authorUniversity of Lethbridge. Faculty of Arts and Science
dc.contributor.supervisorWetmore, Stacey D.
dc.date.accessioned2011-06-15T17:43:55Z
dc.date.available2011-06-15T17:43:55Z
dc.date.issued2009
dc.degree.levelMasters
dc.descriptionxiii, [131] leaves : ill. (some col.) ; 29 cmen_US
dc.description.abstractThe 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.en_US
dc.identifier.urihttps://hdl.handle.net/10133/1292
dc.language.isoen_USen_US
dc.publisherLethbridge, Alta. : University of Lethbridge, Dept. of Chemistry and Biochemistry, c2009en_US
dc.publisher.departmentDepartment of Chemistryen_US
dc.publisher.facultyArts and Scienceen_US
dc.relation.ispartofseriesThesis (University of Lethbridge. Faculty of Arts and Science)en_US
dc.subjectDeoxyribonucleotides -- Synthesisen_US
dc.subjectHydrolysisen_US
dc.subjectChemical engineeringen_US
dc.subjectDNAen_US
dc.subjectDissertations, Academicen_US
dc.titleComputational modeling of the hydrolysis of 2'-deoxyribonucleic acidsen_US
dc.typeThesisen_US
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