Our group is interested in developing and applying new tools based on electrospray ionization mass spectrometry (ESI-MS) and ion mobility to detect and to characterize the structures of proteins and protein complexes. “Native” MS, or the direct measurement of biomolecules from near-physiological solutions by MS, is a major focus of our research efforts.
We are developing MS methods to provide molecular site-specific information. Using “top-down” MS, the direct MS-sequencing of large molecules (without digestion into smaller fragments), we developed an MS-only based method to locate protein-ligand binding sites, and we have extended this work to address the sites of binding of a novel protein aggregation inhibitor that may have application in neurodegenerative diseases.
Structure Elucidation of Proteins and Complexes by Mass Spectrometry
structural biology
Using high resolution MS with various forms of dissociation methods (electron capture dissociation, photodissociation), we have extended top-down MS to address larger protein-ligand and protein-protein complexes. Top-down MS of protein complexes yields sequence information primarily from the outer surface of the complex, suggesting a unique utility for structural biology. Direct information on the presence of disulfide bonds, modifications, and “proteoforms” can be obtained by top-down MS. Our future research will continue to advance mass spectrometry as a tool for structural biology, especially for membrane proteins, and the areas of neurodegenerative diseases and aging.