Peptide Conformation Studies with Vibrational Spectroscopy and Site Selective Isotopic Labeling

University Of Illinois At Chicago, Chicago IL

Investigators

Abstract

This project, funded by the Experimental Physical Chemistry Program of the Chemistry Division, deals with peptide conformations, energetics, and dynamics of protein structure and folding. Most oligopeptides are quite flexible and thereby inhibit conventional structural analyses, especially under conditions where one structure is changing into another, such as folding. To overcome these difficulties Keiderling will conduct a research program to place the interpretation of infrared (IR), Raman, vibrational circular dichroism (VCD) and Raman optical activity, as well as time-dependent Raman and IR spectra experiments on a solid foundation. To this end he will (a) employ isotopically labeled systems to give the vibrational spectra resolved, site-specific character, and (b) develop a more reliable interpretative basis for the vibrational spectral intensity band shapes measured in peptides. The experimental efforts will be aided by DFT augmented Gaussian 98 calculations to obtain spectral parameters for computational modeling of the spectra. Most experimental and computational efforts will focus on beta-hairpin and beta-sheet modeling. Peptides of different lengths with various beta-turn stabilizing residues will be studied while thermally unfolded and refolded. The overall goal of the work is the development of enhanced structural biology tools, both experimental and theoretical, and obtain a basic understanding of folding energetics, capable of addressing broad biophysical needs. This research will be conducted with students and postdoctoral research associates. They will thereby acquire skills and training in one of the fast developing forefront areas of contemporary bio-physical chemistry, in preparation for advanced studies or employment in the scientific/technological sectors of our economy.