The goal of this project is to use site-specific quantitative techniques that have been recently developed in the field of infrared spectroscopy to address several fundamental questions about the alpha-helix-random coil transition as it occurs in short peptides. These questions have become the subject of intense debate in recent years and are relevant to our understanding of early events in protein folding pathways. These issues are also important for understanding the factors that stabilize alpha-helices in peptide hormones and antigens as well as larger systems such as enzymes, antibodies and structural proteins. We intend to directly measure the equilibrium constant(s) for the recruitment of amino acids into propagating alpha-helices and examine how these propensities are modulated by a variety of factors, including sequence-specific interactions, solvent effects and intermolecular interactions. We also intend to examine the thermodynamic parameters that are the basis for differing propagation propensities, and investigate the extent of cooperativity that occurs in helix-coil transitions in short peptide sequences.
