Ultraviolet Raman Studies of Proteins and Nucleic Acids

Princeton University, Princeton NJ

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Abstract

DESCRIPTION (provided by applicant): The dynamical behavior of proteins will be investigated, using time-resolved Raman and infrared spectroscopies as probes of structure in real time. Laser temperature-jump techniques will be applied to the protein folding problem, in order to characterize the earliest stages in folding and unfolding. T-jump studies of the Alzheimers peptide will explore the mechanism of the oligomerization process, which is believed to lead to neurotoxicity. The dynamics of protein allostery will continue to be investigated, using hemoglobin as a paradigm. Pump-probe spectroscopic monitoring of the R-T conformation change will be used to define the reaction coordinate in molecular detail, using isotope labeling, site-directed mutagenesis and metal substitution, in conjunction with computational modeling. By increasing our understanding of hemoglobin, these studies may lead to improved hematological therapies.