William A. Eaton, M.D., Ph.D.


LCP
BIOPHYSICAL CHEMISTRY SECTION
NIDDK, National Institutes of Health
Building 5 , Room 104
5 Memorial Dr.
Bethesda, MD 20814
Tel: 301-496-6030
Fax: 301-496-0825
Email: eaton@helix.nih.gov

William A. Eaton, M.D., Ph.D.

Education / Previous Training and Experience:
B.A., University of Pennsylvania, 1959
Free University of Berlin, 1960
M.D., University of Pennsylvania, 1964
Ph.D., University of Pennsylvania, 1967


Research Statement:
Current research focuses on fundamental aspects of the mechanism of protein folding. A series of novel techniques have been developed to study the dynamics of fast processes in protein folding. These include the use of nanosecond pulsed lasers to trigger and monitor the folding reaction, as well as single molecule fluorescence measurements. Simple models are used to interpret the experimental results and expose the basic underlying physics of these processes. The experimental results and theoretical modeling are providing critical benchmarks for the construction of a detailed picture of the sequence of events as a protein forms its native conformation from the random structures of the unfolded polypeptide chain.  We continue to study the mechanism of sickle cell hemoglobin aggregation and its relation to the molecular pathophysiology and treatment of sickle cell disease.


Selected Publications:

Chung HS, Louis JM, and Eaton WA. Single-molecule fluorescence experiments determine protein folding transition path times. Science (335): 981-984, 2012.

Cellmer T, Buscaglia M, Henry ER, Hofrichter J, Eaton WA. Making connections between ultrafast protein folding kinetics and molecular dynamics simulations. Proc Natl Acad Sci USA (108): 6103–6108, 2011.

Chung HS, Gopich IV, McHale K, Cellmer T, Louis JM, Eaton WA. Extracting rate coefficients from single-molecule photon trajectories and FRET histograms for a fast-folding protein.J Phys Chem A (115): 3642-3656, 2011.

Chung HS, Louis JM, Eaton WA. Experimental determination of upper bound for transition path times in protein folding from single molecule photon-by-photon trajectories. Feature Article in Proc Natl Acad Sci USA (106): 11837-11844, 2009. Commentary by Eugene Shakhnovich, pp. 11823-11824.

Kubelka J, Henry ER, Cellmer T, Hofrichter J, Eaton WA. Chemical, physical, and theoretical kinetics of an ultrafast folding protein. Proc Natl Acad Sci USA (105): 18655-18662, 2008.

Cellmer T, Henry ER, Hofrichter J, Eaton WA Measuring internal friction in ultra-fast protein folding kinetics. Proc Natl Acad Sci USA (105): 18320-18325, 2008.

Schuler B, Eaton WA Protein folding studied by single-molecule FRET. Curr Opin Struct Biol (18): 16-26, 2008.

4Best RB, Merchant KA, Gopich IV, Schuler B, Bax A, Eaton WA Effect of flexibility and cis residues in single molecule FRET studies of polyproline. Proc Natl Acad Sci USA (104): 18964-18969, 2007.

Cellmer T, Henry ER, Kubelka J, Hofrichter J, Eaton WA Relaxation rate for an ultrafast folding protein is independent of chemical denaturant concentration. J Amer Chem Soc (129): 14564-14565, 2007.

Eaton WA, Henry ER, Hofrichter J, Bettati S, Viappiani C, Mozzarelli A Evolution of allosteric models for hemoglobin. IUBMB Life (58): 586-599, 2007.

Merchant KA, Best RB, Louis JL, Gopich IV, Eaton WA Characterizing the unfolded states of proteins using single molecule FRET spectroscopy and molecular simulations. Proc Natl Acad Sci USA (104): 1528-1533, 2007.

Kubelka J, Chiu TK, Davies DR, Eaton WA, Hofrichter J Sub-microsecond protein folding. J Mol Biol (359): 546-553, 2006.

Christoph GW, Hofrichter J, Eaton WA Understanding the shape of the sickled red cell. Biophy J (88): 1371-1376, 2005.

Henry ER, Eaton WA Combinatorial modeling of protein folding kinetics: free energy profiles and relative rates. Chem. Phys. (307): 163-185, 2004.

Viappiani C, Bettati S, Bruno S, Ronda L, Abbruzzetti S, Mozzarelli A, Eaton WA New insights into allosteric mechanisms from trapping unstable protein conformations in silica gels. Proc Natl Acad Sci U S A (101): 14414-9, 2004. [Full Text/Abstract]

Kubelka J, Hofrichter J, Eaton WA The protein folding ''speed limit''. Curr Opin Struct Biol (14): 76-88, 2004. [Full Text/Abstract]

Eaton WA Linus Pauling and sickle cell disease. Biophys Chem (100): 109-16, 2003. [Full Text/Abstract]

Lipman EA, Schuler B, Bakajin O, Eaton WA Single-molecule measurement of protein folding kinetics. Science (301): 1233-5, 2003. [Full Text/Abstract]

Henry ER, Bettati S, Hofrichter J, Eaton WA A tertiary two-state allosteric model for hemoglobin. Biophys Chem (98): 149-64, 2002. [Full Text/Abstract]

Schuler B, Lipman EA, Eaton WA Probing the free-energy surface for protein folding with single-molecule fluorescence spectroscopy. Nature (419): 743-7, 2002. [Full Text/Abstract]

Lapidus LJ, Eaton WA, Hofrichter J Dynamics of intramolecular contact formation in polypeptides: distance dependence of quenching rates in a room-temperature glass. Phys. Rev. Lett. (87): 258101-1 - 258101-4, 2001.

Eaton WA, Munoz V, Hagen SJ, Jas GS, Lapidus LJ, Henry ER, Hofrichter J Fast kinetics and mechanisms in protein folding. Annu Rev Biophys Biomol Struct (29): 327-59, 2000. [Full Text/Abstract]

Eaton WA Hofrichter J Sickle cell hemoglobin polymerization. Adv Protein Chem (40): 63-279, 1990. [Full Text/Abstract]




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Page last updated: April 17, 2012

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