With support from the Chemical Measurement and Imaging Program in the Division of Chemistry, Professor Kristina Hakansson and her group at the University of Michigan are working to improve our ability to characterize the chemical structure of molecules, including especially biomolecules such as proteins. Such structural analysis is essential to help us understand the function (and dysfunction) of molecules in complex samples, e.g., biofluids, cells, and tissues. The Hakansson approach employs the attachment of electrons to gaseous anions (negatively charged molecules), inducing diagnostic fragmentation of the target molecule in a process termed negative ion electron capture dissociation (niECD). Adding electrons (which bear a negative charge) to anions (which also are negatively charged) is challenging, due to charge repulsion. Having developed this method, Dr. Hakansson is now working to improve our understanding and broaden the applicability and availability of niECD. The research is providing new approaches to biomolecular structural characterization with important implications for drug discovery and enhanced understanding of the molecular basis of living organisms. Students involved gain exposure to highly interdisciplinary research. Dr. Hakansson also works to bring appreciation for these concepts and for broader STEM opportunities to middle school students in an effort to boost interest in the scientific method at a young age.
The Hakansson group is exploring novel niECD instrument configurations, including extension to matrix-assisted laser desorption/ionization and nano-electrospray ionization. They are working to implement niECD in a high pressure cell, enabling use with mass analyzers other than Fourier transform ion cyclotron resonance (FT-ICR). In pursuit of improved insight into the fundamental chemistry underlying niECD, they are pursuing two approaches (drift tube ion mobility and cross-sectional areas by FT-ICR, or CRAFTI (cross-sectional areas by FT-ICR) to testing Dr. Hakansson?s recent findings that compact, presumably salt-bridged structures are required for effective niECD of peptides. These efforts are supported by molecular modeling and density functional theory calculations, with a special focus on novel analyte classes such as carbohydrates and lipids, which were recently discovered by the Hakansson group to undergo niECD despite not fitting the previously proposed zwitterion mechanism.
This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.
