Characterizing Protein Dynamics of Protein-Ligand Interactions by Hydrogen-Deuterium Exchange Mass Spectrometry

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dc.contributor.advisorWilson, Derek J.
dc.creatorResetca, Diana
dc.date.accessioned2015-01-26T15:09:10Z
dc.date.available2015-01-26T15:09:10Z
dc.date.copyright2014-08-19
dc.date.issued2015-01-26
dc.date.updated2015-01-26T15:09:10Z
dc.degree.disciplineChemistry
dc.degree.levelMaster's
dc.degree.nameMSc - Master of Science
dc.description.abstractThe study of protein-ligand and protein-protein interactions is of paramount importance to the understanding of their biological function. Whereas this area of research has been largely dominated by conventional structural biology techniques, such as NMR and X-ray crystallography, an emerging methodology that relies on the implementation of hydrogen deuterium exchange (HDX) powered by MS-based analysis holds the potential to greatly expand on our ability to probe the protein dynamics of fundamental biological processes. In this work, the entire HDX workflow for site-specific analysis of protein dynamics was integrated onto a concerted microfluidic device and applied to the interrogation of the dynamic changes that accompany protein-ligand interactions. This application is described for two model systems: the binding of glutathione (GSH) by Glutathione-S-Transferase (GST), and the binding of three novel salicylic acid-based inhibitors of Signal Transducer and Activator of Transcription 3 (STAT3) to its SH2 domain. This work extends the application of time-resolved electrospray ionization mass spectrometry (TRESI-MS) HDX to the study of protein ligand interaction dynamics and ligand-binding site mapping.
dc.identifier.urihttp://hdl.handle.net/10315/28269
dc.language.isoen
dc.rightsAuthor owns copyright, except where explicitly noted. Please contact the author directly with licensing requests.
dc.subjectBiochemistry
dc.subjectBiophysics
dc.subjectChemistry
dc.subject.keywordsDimerization inhibitoren_US
dc.subject.keywordsHydrogen exchange mass spectrometryen_US
dc.subject.keywordsSignal transducers and activators of transcription 3 (STAT3)en_US
dc.subject.keywordsMass spectrometry (MS)en_US
dc.subject.keywordsProtein dynamicsen_US
dc.subject.keywordsAllosteric regulationen_US
dc.titleCharacterizing Protein Dynamics of Protein-Ligand Interactions by Hydrogen-Deuterium Exchange Mass Spectrometry
dc.typeElectronic Thesis or Dissertationen_US

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