CAREER: Ion Mobility Spectrometry - Mass Spectrometry for de novo Protein Structure Elucidation

Florida State University, Tallahassee FL

Investigators

Abstract

With support from the Chemical Measurement and Imaging Program in the Division of Chemistry and co-funding from the Chemistry of Life Processes Program (Division of Chemistry) and the Molecular Biophysics Cluster (Division of Molecular and Cellular Biosciences), Professor Christian Bleiholder and his group at Florida State University are developing new tools to characterize the structures of proteins that play critical roles in the chemistry of both normal and abnormal (diseased) cells. These tools - which combine and enhance the capabilities of ion mobility and mass spectrometric measurements - may provide new biochemical insights which have thus far not been possible to obtain with existing tools. This in turn may offer new insights into the functioning of cells and the causes of disease. Impact is enhanced through interactions with academic and industrial collaborators, and by broad dissemination of ideas and results (including software tools) to potential users through websites, workshops, and tutorials. Students working on the projects are trained in instrumentation, computational methods, biochemistry, and analysis of complex data. Transiently populated conformations of proteins and their assemblies play important roles in the function (and misfunction) of cells. Ion mobility spectrometry - mass spectrometry (IMS-MS) methods have recently been shown to be capable of studying such transient conformations but still suffer from two major shortcomings: the relationship between the protein structure elucidated by IMS-MS and the biologically active structure in solution is poorly understood, and detailed protein structures are largely inaccessible from IMS-MS data. Dr. Bleiholder and his team are approaching these challenges by developing new experimental and computational approaches for obtaining and interpreting time-resolved IMS-MS data. To assess the accuracy of protein structure elucidation from IMS-MS data, the team is assessing how long and to what extent native protein structures can be retained in the gas phase. Computational methods are being developed and assessed for their ability to identify the structure of a protein from only its cross section distribution. Finally, the developed computational methods is disseminated in a form that is easy to use by non-experts in order to enable a wider IMS-MS community to elucidate protein structures accurately.