A Chemical Modification- and Mass Spectrometry-Based Method for Thermodynamic Analysis of Protein-Ligand Binding

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This award is funded under the American Recovery and Reinvestment Act of 2009 (Public Law 111-5).The Divisions of Chemistry and Molecular and Cellular Biosciences support Professor Michael Fitzgerald of Duke University to develop and apply a mass spectrometry-based method known as SPROX (Stability of Proteins from Rates of Oxidation) to assess protein folding and the thermodynamic stability of protein-ligand complexes. Protocols are being optimized for model proteins and their ligands, and will then be extended to the analysis of protein-ligand binding in real biological mixtures (e.g., yeast cell lysates). The assay to be developed should have unmatched multiplex capabilities. It will create a unique opportunity to detect not only direct but also indirect binding, wherein binding of a target ligand to one protein either precludes or induces binding a second protein.The strategies and protocols to be created will be readily transferable to almost any protein-ligand system or biological mixture regardless of the ligand (i.e. small molecule, DNA, peptide, or other proteins) or binding affinity. The research provides interdisciplinary research experiences for both graduate and undergraduate students, and as well as high school students from the North Carolina Project SEED program, which is an on-going science enrichment program designed to steer disadvantaged, underrepresented minority students from North Carolina high schools into chemistry and chemistry-related careers.