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dc.contributor.advisorBaker, David
dc.contributor.authorUeda, George Thomas
dc.date.accessioned2019-02-22T17:02:47Z
dc.date.available2019-02-22T17:02:47Z
dc.date.submitted2018
dc.identifier.otherUeda_washington_0250E_19461.pdf
dc.identifier.urihttp://hdl.handle.net/1773/43303
dc.descriptionThesis (Ph.D.)--University of Washington, 2018
dc.description.abstractUsing a newly developed computational docking and scoring method combined with Rosetta two-sided interface design, we demonstrated accurate design of self-assembling oligomeric proteins that exhibit various degrees of symmetry. A set of designs were validated to match their respective models at the atomic-scale and we progressed to functionalize this class of proteins for targeted biological applications. With the unique ability to tailor new protein structures, we span a diversity of controllable geometric arrangements representing a molecular toolkit to probe biological systems at the subnanometer scale. Presented in this dissertation are examples of next-generation vaccine candidates that scaffold entire antigenic complexes, as well as potential biotherapeutics that activate signaling pathways through engagement and tunable clustering of cell surface receptors. These studies showcase the potential for computationally-generated molecules to trigger unique biological responses, providing novel insights, considerations, and future avenues for vaccine and biotherapeutic development across various disease spaces.
dc.format.mimetypeapplication/pdf
dc.language.isoen_US
dc.relation.haspartCyclic_design_models.zip; other; Desiged homooligomer .pdb models from C2-C5 symmetry.
dc.relation.haspartCyclic_docking_design_examples.zip; code/script; Example command lines in, motif database and scores for docking, RosettaScripts two-sided interface design .xml file, and required flags files.
dc.rightsnone
dc.subjectBiotherapeutic
dc.subjectComputational
dc.subjectDesign
dc.subjectEngineering
dc.subjectProtein
dc.subjectVaccine
dc.subjectBiochemistry
dc.subjectBioengineering
dc.subjectComputational chemistry
dc.subject.otherBiological chemistry
dc.titleComputational Design of Symmetric Protein Complexes with Implications for Vaccine and Biotherapeutic Development
dc.typeThesis
dc.embargo.termsOpen Access


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