The kinetics and mechanism of protein folding is being studied using a variety of laser techniques. These include measuring the rate of a specific intramolecular contact from quenching of tryptophan fluorescence by cysteine, measurements of equilibria and kinetics of an ultra-fast folding protein (villin subdomain) using laser temperature jump, and single molecule fluorescence measurements of a two-state folder (cold shock protein) to obtain dynamical information for determination of entropy barriers to folding. The results are being used to develop analytical statistical mechanical models of protein folding and to test the results of molecular dynamics simulations.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Intramural Research (Z01)
Project #
1Z01DK029010-31
Application #
6810173
Study Section
(LCP)
Project Start
Project End
Budget Start
Budget End
Support Year
31
Fiscal Year
2003
Total Cost
Indirect Cost
Name
U.S. National Inst Diabetes/Digst/Kidney
Department
Type
DUNS #
City
State
Country
United States
Zip Code
Godoy-Ruiz, Raquel; Henry, Eric R; Kubelka, Jan et al. (2008) Estimating free-energy barrier heights for an ultrafast folding protein from calorimetric and kinetic data. J Phys Chem B 112:5938-49
Schuler, Benjamin; Eaton, William A (2008) Protein folding studied by single-molecule FRET. Curr Opin Struct Biol 18:16-26
Cellmer, Troy; Henry, Eric R; Kubelka, Jan et al. (2007) Relaxation rate for an ultrafast folding protein is independent of chemical denaturant concentration. J Am Chem Soc 129:14564-5
Buscaglia, Marco; Lapidus, Lisa J; Eaton, William A et al. (2006) Effects of denaturants on the dynamics of loop formation in polypeptides. Biophys J 91:276-88
Kubelka, Jan; Chiu, Thang K; Davies, David R et al. (2006) Sub-microsecond protein folding. J Mol Biol 359:546-53
Munoz, Victor; Ghirlando, Rodolfo; Blanco, Francisco J et al. (2006) Folding and aggregation kinetics of a beta-hairpin. Biochemistry 45:7023-35
Christoph, Garrott W; Hofrichter, James; Eaton, William A (2005) Understanding the shape of sickled red cells. Biophys J 88:1371-6
Schuler, Benjamin; Lipman, Everett A; Steinbach, Peter J et al. (2005) Polyproline and the ""spectroscopic ruler"" revisited with single-molecule fluorescence. Proc Natl Acad Sci U S A 102:2754-9
Buscaglia, Marco; Kubelka, Jan; Eaton, William A et al. (2005) Determination of ultrafast protein folding rates from loop formation dynamics. J Mol Biol 347:657-64
Chiu, Thang K; Kubelka, Jan; Herbst-Irmer, Regine et al. (2005) High-resolution x-ray crystal structures of the villin headpiece subdomain, an ultrafast folding protein. Proc Natl Acad Sci U S A 102:7517-22

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