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

University Of California-Irvine, Irvine CA

Investigators

Abstract

In this award the Chemistry of Life Processes Program supports Professor Nien-Hui Ge of the University of California at Irvine to 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, and elucidating protein-membrane interactions. MultiD IR experiments 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 and incorporating IR probes at selected locations 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 are investigated to understand the factors that control protein stability. Proteins, long chains of peptides, fold rapidly into complex shapes that affect their function and how they bind with other molecules. Detailed knowledge of peptides and larger proteins - structure, dynamics, and folding can shed light on protein misfolding that characterizes many diseases. Understanding how proteins interact with membranes also informs the design of novel functional molecules, potentially useful for medicine. MultiD IR spectroscopy is a laser technique that can determine the shape and behavior of a peptide by studying the infrared light emitted after it was "photographed" using laser pulses at a "shutter speed" faster than one trillionth of a second. Graduate students and postdoctoral researchers participating in the research gain valuable experience with advanced laser techniques and core physical sciences that can strengthen their future career development. This project is also integrated with outreach efforts on maintaining an online spectrum database and contributing lectures and laboratory courses for K-12 students.