Computational insight into the broad substrate specificity of enzymes that process nucleic acids

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dc.contributor.authorLenz, Stefan
dc.contributor.authorUniversity of Lethbridge. Faculty of Arts and Science
dc.contributor.supervisorWetmore, Stacey D.
dc.date.accessioned2019-03-27T20:43:35Z
dc.date.available2019-03-27T20:43:35Z
dc.date.issued2018
dc.degree.levelPh.Den_US
dc.description.abstractMany enzymes that bind DNA and RNA possess broad substrate specificity and play diverse roles in biology. Three classes of enzymes with broad substrate specificity are nucleoside hydrolases that salvage nucleic acid building blocks, and alkyladenine DNA glycosylases (AAG) and AlkB enzymes, which repair alkylated and/or deaminated DNA damage. This thesis uses advanced computational techniques to examine how enzymes process structurally diverse substrates. Specifically, structural and energetic information is provided by molecular dynamics (MD) simulations, quantum mechanics (QM) and hybrid quantum mechanics/molecular mechanics (QM/MM) calculations, which provide insight into how each enzyme active site changes to accommodate unique substrates and quantify the impact that these changes have on catalyzed reactions. From these results, atomistic explanations for the activity of these enzymes is obtained, which can be used to develop new treatments for diseases. The computational approach presented can be applied to other enzymes that exhibit broad substrate specificity.en_US
dc.embargoNoen_US
dc.identifier.urihttps://hdl.handle.net/10133/5302
dc.language.isoen_USen_US
dc.proquest.subject0487en_US
dc.proquest.subject0494en_US
dc.proquest.subject0572en_US
dc.proquestyesYesen_US
dc.publisherLethbridge, Alta. : University of Lethbridge, Department of Chemistry and Biochemistryen_US
dc.publisher.departmentDepartment of Chemistry and Biochemistryen_US
dc.publisher.facultyArts and Scienceen_US
dc.relation.ispartofseriesThesis (University of Lethbridge. Faculty of Arts and Science)en_US
dc.subjectEnzymes -- Research -- Computer simulationen_US
dc.subjectNucleosides -- Research -- Computer simulationen_US
dc.subjectHydrolases -- Research -- Computer simulationen_US
dc.subjectDNA ligases -- Research -- Computer simulationen_US
dc.subjectNucleic acids -- Research -- Computer simulationen_US
dc.subjectDissertations, Academicen_US
dc.subjectAlkB enzymesen_US
dc.subjectalkyladenine DNA glycosylasesen_US
dc.subjectbroad substrate specificityen_US
dc.subjectenzymesen_US
dc.subjectnucleoside hydrolasesen_US
dc.subjectsubstrate processingen_US
dc.titleComputational insight into the broad substrate specificity of enzymes that process nucleic acidsen_US
dc.typeThesisen_US
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