Protein Structure, Dynamics, and Folding via Ultrafast Multidimensional Infrared Spectroscopy

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In this award supported by the Chemistry of Life Processes Program, Professor Nien-Hui Ge of the University of California at Irvine will use femtosecond multidimensional infrared (MultiD IR) spectroscopy to study the conformational dynamics, distributions, and folding of peptides. The goal is to provide detailed knowledge of protein structure and dynamics that is essential to the understanding of biological processes. The proposed work includes investigating the interplay between helical and extended structures, determining conformational distributions of nonfolding peptides, studying the association of supercoiled protein motifs, and elucidating protein-membrane interactions. MultiD IR experiments will access the backbone and side chain vibrational modes of peptides, and provide data that reveal the angles, distances, and correlations between structural units. Isotope editing at selected locations will be employed to enhance the spatial resolution, facilitate the assignment of resonances, and extend the method to larger peptides and tertiary contacts. The effects of temperature, pH, solvent, and chain length will be investigated to understand the factors that control protein stability. MultiD IR spectroscopy is a relatively new technique that complements NMR and X-ray methods, with the capability of probing the structure in situ as it evolves over a wide range of time scales, from femtosecond to millisecond. Applying this technique to the study of peptides will allow us to gain insights into rapid conformational fluctuations and transitions, not readily amenable to conventional techniques. Such experimental data are much needed for verification of theoretical predictions and validation of the next generation of force fields. Further development of two-color MultiD IR methods, analogous to heteronuclear NMR, will allow direct probing of coupling between vibrators of very different frequencies. Its application to the amide vibrational modes will enable conformational determination with higher accuracy. These studies will provide detailed information on peptide structure and dynamics, and contribute to the understanding of protein folding. Graduate students and postdoctoral researchers participating in the research will gain valuable experience with advanced laser techniques and core physical sciences that can strengthen their future career development. Efforts on maintaining an online spectrum database and contributing lectures and laboratory courses for K-12 students will be continued.