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dc.contributor.authorTessier, Matthew Bruce
dc.date.accessioned2014-07-08T04:30:16Z
dc.date.available2014-07-08T04:30:16Z
dc.date.issued2013-12
dc.identifier.othertessier_matthew_b_201312_phd
dc.identifier.urihttp://purl.galileo.usg.edu/uga_etd/tessier_matthew_b_201312_phd
dc.identifier.urihttp://hdl.handle.net/10724/30032
dc.description.abstractComplex carbohydrates (glycans) have long been known to play a role in immune response, regulation of cellular activity, and cell-cell interactions, to name a few. Thus the ability to model glycan structure and their interactions with other biomolecules (i.e. biorecognition) is essential to understanding and exploiting glycan functionality in the design of pharmaceutical glycomimetics, or molecules with similar properties to glycans. Over several decades, computational methods have become essential to characterizing glycan structure and bioactivity when only sparse experimental data is available. This work expands on those efforts by improving on the GLYCAM molecular mechanics force field to include a wider range of glycan structures including glycolipids and glycosaminoglycans. The GLYCAM force field was used in molecular dynamics (MD) simulations to predict the three-dimensional (3D) structures of glycans and glycoconjugates. Then, utilizing the three-dimensional glycan structure data from glycan simulations and experimental data, a virtual glycan 3D structure library was generated. In this case, the virtual library was employed to establish the first computational prediction of bulk carbohydrate-protein specificity using a method called Computational Carbohydrate Grafting (CCG). This method has been shown to be useful in augmenting the results of experimental specificity screening and it can be used to test the specificity of glycans which are not included on the experimental arrays while providing 3D structures of protein-carbohydrate complexes. The CCG method was used to predict the binding specificity restrictions of the anti-tumor antibody JAA-F11 and provided a 3D structural rational for its binding specificity. The development of the force field and CCG method are all part of an effort to better understand how the 3D structure of glycans impact biorecognition so as to guide the development of novel therapeutic or diagnostic glycomimetics.
dc.languageeng
dc.publisheruga
dc.rightspublic
dc.subjectComputational carbohydrate grafting
dc.subjectGLYCAM
dc.subjectGlycosaminoglycans
dc.subjectGlycolipids
dc.subjectLipids
dc.subjectCarbohydrates
dc.subjectGlycans
dc.subjectForce field parameter development
dc.subjectVirtual glycan array
dc.subjectVirtual docking
dc.subjectMolecular mechanics
dc.subjectAntibody binding
dc.subjectGlycan array
dc.subjectNMR
dc.titleThe development of computational carbohydrate grafting and the GLYCAM force field to understand how glycan structure alters biorecognition
dc.typeDissertation
dc.description.degreePhD
dc.description.departmentChemistry
dc.description.majorChemistry
dc.description.advisorRobert Woods
dc.description.committeeRobert Woods
dc.description.committeeGeoffrey D. Smith
dc.description.committeeJames Prestegard


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