2026-09-25T04:15:50.912603300Zhttps://opus.uleth.ca/server/oai/requestoai:opus.uleth.ca:10133/12922019-03-27T20:26:33Zcom_10133_3346com_10133_1com_10133_296col_10133_3347col_10133_298
ULethbridge OPUS Repository
supervisor
Wetmore, Stacey D.
author
Przybylski, Jennifer L.
author
University of Lethbridge. Faculty of Arts and Science
2011-06-15T17:43:55Z
2011-06-15T17:43:55Z
2009
https://hdl.handle.net/10133/1292
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.
en_US
Deoxyribonucleotides -- Synthesis
Hydrolysis
Chemical engineering
DNA
Dissertations, Academic
Computational modeling of the hydrolysis of 2'-deoxyribonucleic acids
Thesis
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PRZYBYLSKI_JENNIFER_MSC_2009.pdf.txt