Computational studies of protein posttranslational modification : glycosylation of oligoproline and collagen peptides

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dc.contributor.authorNaziga, Emmanuel B.
dc.contributor.supervisorWetmore, Stacey D.
dc.date.accessioned2014-07-31T17:30:34Z
dc.date.available2014-07-31T17:30:34Z
dc.date.issued2013
dc.degree.levelPh.Den_US
dc.degree.levelPhD
dc.descriptionxvi, 238 leaves : ill. ; 29 cmen_US
dc.description.abstractGlycosylation is the most complex posttranslational modification of proteins and has consequences on protein structure and function. In particular, the hydroxyproline (Hyp) rich glycoproteins (HRGPs) of plants are heavily glycosylated. On the other hand, glycosylation has not been observed in animal collagen despite the high occurrence of Hyp residues. This thesis uses computational chemistry to provide molecular level information about the structural effects of Hyp glycosylation to help understand the biological implications of the modification and explain the lack of glycosylation in animals. Initially, the nature of the glycosidic linkage between Hyp and galactose was determined. The theoretical results were validated by comparing to the recent experimental data, which helped understand other experimental observations. Subsequently, contiguous and non-contiguous glycosylation of a nonaproline oligopeptide was considered, which revealed that contiguous glycosylation increases the stability of the all trans polyproline II (PPII) conformation, while non-contiguous glycosylation leads to loss of PPII content. Sophisticated modeling suggested that this difference arises since peptide–solvent interactions stabilize the PPII conformation in the contiguously glycosylated peptide, while sugar–peptide backbone interactions that stabilize the cis conformations of some residues are stronger in the non-contiguously glycosylated peptide. Finally, the effects of Hyp glycosylation on the collagen triple helix were assessed, where it was determined that glycosylation makes the monomeric state more stable and hence hinders triple helix formation, which agrees with experimental results and highlights that the synergy between computation and experiments is necessary to understand complex glycosylation in nature.en_US
dc.identifier.urihttps://hdl.handle.net/10133/3474
dc.language.isoen_CAen_US
dc.proquestyesNoen_US
dc.publisherLethbridge, Alta. : University of Lethbridge, Dept. 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.subjectPost-translational modification -- Computer simulationen_US
dc.subjectPost-translational modification -- Researchen_US
dc.subjectGlycosylation -- Researchen_US
dc.subjectGlycoproteins -- Researchen_US
dc.titleComputational studies of protein posttranslational modification : glycosylation of oligoproline and collagen peptidesen_US
dc.typeThesisen_US
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