PEPTIDE AND PROTEIN STRUCTURE EVOLUTION BY 2-D IR

University Of Pennsylvania, Philadelphia PA

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Abstract

Novel experiments using two-dimensional infrared (2D IR) spectroscopy are proposed to study the real time dynamics of protein folding events. This method will allow us to monitor three-dimensional protein structure on the sub-microsecond time scale of the folding process. New insight into the time scales, mechanisms, and topologies of protein landscapes is expected. Analogous to 2D NMR, 2D IR spectroscopy is a new technique that shows promise for determining three-dimensional protein structure through a vibrational coupling between amide bonds along the protein backbone. In this technique, a subset of amide oscillators in the amide I band is excited, and the affects on the frequencies of other, nearby amide oscillators is monitored. Since the coupling is sensitive to the amide orientations and distances, the resulting spectra relate to the three- dimensional protein structure, and because the intrinsic time resolution of this technique is less than 1 ps, it is capable to determining structure on all biologically relevant time scales. The first two phases of the proposal will test and improve the technique with experiments on small de novo peptides. In the final phase, the improve technique will be applied to the sub-millisecond folding of a 19 residue alpha-helix.