Characterization of the Dynamics of Beta Sheet Formation by Time-Resolved Infrared Spectroscopy and Computational Modeling

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Title: Characterization of the Dynamics of Beta Sheet Formation by Time-Resolved Infrared Spectroscopy and Computational Modeling
Author: Maness, Shelia Jane
Advisors: Stefan Franzen, Committee Chair
Carol A. Haney, Committee Member
Charles B. Boss, Committee Member
Morteza G. Khaledi, Committee Member
Abstract: Limited solubility of beta hairpin models prevents a good understanding of their formation. However, beta sheet peptides were recently designed with improved solubility allowing spectroscopic study as models for beta hairpins in larger proteins. The dynamics of cyclic analogs of gramicidin S and two unconstrained beta sheet peptides, H1a and H3, were studied using both a static, temperature-dependent FTIR technique and nanosecond time-resolved infrared spectroscopy. Quench dynamics and density functional theory (DFT) calculations were used to complement the experimental work and to aid in the analysis of two of the cyclic peptides. The folding rates of cyclic peptides are accelerated by at least an order of magnitude over the rates of linear beta hairpin peptides suggesting that nucleation of the folding event is the rate-determining step. The kinetic data for H1a and H3 were analyzed using singular value decomposition (SVD). The H1a peptide has two observed relaxation rates corresponding to several hundreds of nanoseconds and a few microseconds while the H3 peptide fit to a two-state model with a microsecond observed lifetime. Both nucleation and propagation components of folding were measured in these studies, and the results present a complete hypothesis for the sequence of events in beta sheet formation.
Date: 2003-07-29
Degree: PhD
Discipline: Chemistry
URI: http://www.lib.ncsu.edu/resolver/1840.16/3231


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