The Experimental Physical Chemistry program of the Division of Chemistry supports the research of Professor Timothy Keiderling of the Department of Chemistry, University of Illinois at Chicago. Using infrared, Raman, vibrational circular dichroism (VCD), and fluorescence techniques, Keiderling and his students will study flexible peptide molecules of different lengths and varying sequences of amino acid residues that are designed to fold into beta-hairpin structures. These molecules will provide models for the study of the elementary steps in beta-sheet folding. The project will emphasize the use of polypeptides, selectively labeled with carbon-13, which can be studied with IR, Raman, or VCD spectroscopy to determine site-specific, local peptide structures. Conformational changes will be induced by varying the temperature, solvent, and pH under equilibrium conditions. Time-dependent, temperature jump spectroscopy will be used to investigate the dynamics of unfolding the peptide structure. These experiments will be combined with ab-initio quantum mechanical calculations to model short- and long-range interactions between peptide bonds in molecules with a variety of conformations. Molecular dynamics methods will be employed to simulate the mechanisms for polypeptide folding. Beta-sheets are critical components for several toxic mis-folded peptide and protein states. The information gained from these studies will improve our understanding of protein folding and impact areas of biochemistry and structural biology.
