The National Institute of Diabetes & Digestive & Kidney Diseases

We are interested in the nature and characteristic time scales of conformational changes in proteins. This broad question encompasses both the structural events involved in the initial folding of the polypeptide chain into its native structure in solution and the structural changes associated with protein function. In one study we are analyzing the measured equilibrium and kinetic properties of the folding of various proteins using simple statistical-mechanical models in an attempt to elucidate basic physical principles underlying the folding process. We have also long been involved in studies of the dynamics of functionally relevant conformational changes in heme proteins, historically using time-resolved optical spectroscopic probes to detect and measure the kinetics of these changes and molecular dynamics simulations to attempt to identify the actual atomic motions involved; most recently we have been involved in using time-resolved X-ray crystallography to visualize the atomic motions directly.

1. 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]

2. Eaton WA, Henry ER, Hofrichter J, Mozzarelli A Is cooperative oxygen binding by hemoglobin really understood? Nat Struct Biol(6): 351-8, 1999. [Full Text/Abstract]

3. Henry ER, Jones CM, Hofrichter J, Eaton WA Can a two-state MWC allosteric model explain hemoglobin kinetics? Biochemistry(36): 6511-28, 1997. [Full Text/Abstract]

4. Henry ER The use of matrix methods in the modeling of spectroscopic data sets. Biophys J(72): 652-73, 1997. [Full Text/Abstract]