Collaborative Research: Development of 2D IR Spectroscopy as a Quantitative Probe of Protein Structure, with Applications to Membrane and Aggregated Proteins

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Prof. Martin Zanni at the University of Wisconsin in Madison, and collaborators James Skinner (UW-Madison), Daniel Raleigh (SUNY at Stony Brook), and Sean Decatur (Oberlin College) are supported by the Collaborative Research in Chemistry Program to devise and test methods based on two-dimensional infrared (2D IR) spectroscopy for characterization of protein structure and function. The techniques are particularly important for studying systems for which NMR and x-ray crystallography are difficult to apply, such as proteins in cell membranes and protein aggregates. The work brings together a diverse and complementary team of researchers to develop a rigorous protocol for calculating 2D IR spectra from atomistic structural models through a novel combination of theory, experiment, and synthesis. To develop the theoretical methodology, well-characterized proteins are either isotope-labeled or mutated at individual residues so that the linewidths and/or couplings of specific residues can be measured with 2D IR spectroscopy. While the work is primarily directed toward developing 2D IR as a tool for protein kinetics, it can be applied to other systems as well. Undergraduate and graduate students and postdocs involved in this study are being trained to work in a collaborative interdisciplinary and inter-institutional environment. Participation of underrepresented groups derives from exchange programs among Oberlin, Howard University, Stony Brook, and Wisconsin. Cyber-infrastructure components include web-conferences to discuss research progress and dissemination of user-friendly software for the theoretical calculation of spectra. An undergraduate physical chemistry lab experiment is being developed to show how FTIR spectroscopy can be used as a tool for protein secondary structure determination; the experiment will be tested in the physical chemistry lab courses at Wisconsin, Stony Brook, Oberlin, and Howard, and then made available to the broader academic community. Institutions that lack the needed instrumentation will be able to incorporate this experiment into their curriculum by taking advantage of the web-based remote access features being developed.