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 to characterize the size and dynamics of the unfolded state of two-dtate folding proteins (CspTm and protein L). The results are being used in the developemnt of analytical statistical mechanical models of protein folding and to test the results of molecular dynamics simulations. The dynamics of islet amyloid polypeptide are being studied by quenching of the tryptophan triplet state by cystine. A new project has been initiated in collaboration with Dr. Jeffery Miller on the development of a sensitive kinetic assay for large scale screening of potential drugs for sickle cell disease. Collaborative research on cooperativity in multisubunit proteins has continued with the Parma group.
| 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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