Time-resolved infrared and fluorescence spectroscopic studies of protein dynamics and structure

While the structure of a particular folded protein is a direct outcome of the underlying thermodynamics, arriving at a quantitative and predictive understanding of how this folded structure is reached nevertheless poses huge challenges. Among those challenges is the need for probes of protein folding that possess both high temporal and structural resolution. To this end, this Thesis reports studies performed on a number of model peptide and protein systems aimed at applying novel spectroscopic techniques and molecular probes to the task of acquiring highly detailed information about either the mechanism of folding or the nature of the native protein structure.;The earlier chapters of this Thesis present studies on the utility of the artificial amino-acid p-cyanophenylalanine as a time-resolved fluorescence and energy-transfer probe of local protein structure. Application of this probe to the villin headpiece subdomain revealed new details about the native state ensemble of this mini-protein.;The later chapters report the findings of a number of time-resolved laser temperature-jump experiments on model helical peptides as well as on the mini-protein Trp-Cage. These experiments provide benchmarks for some of the elementary kinetic events of helix formation for the former and detailed insight into the folding mechanism of one of the fastest folding proteins known to date for the latter.