- Ph.D., Princeton University, 1980
- M.A., Princeton University, 1978
- B.S. and B.A., University of Rochester, 1976
The goal of this research is to understand the physics underlying the structure and dynamics of proteins and their relationship to biological function.
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. In this study, we use simple statistical-mechanical models in an attempt to elucidate basic physical principles underlying the folding process. We are also examining the dynamics of functionally relevant conformational changes in heme proteins. We use time-resolved optical spectroscopic probes to detect and measure the kinetics of these changes and molecular dynamics simulations to identify the actual atomic motions involved. Most recently, we have used time-resolved x-ray crystallography to visualize atomic motions directly.
Applying our Research
A detailed understanding of the functionally relevant structural and dynamical properties of proteins is, among other things, a core component of the rapidly expanding field of rational drug design. In this field, knowledge of the molecular basis of pathology informs the de novo molecular design of targeted therapeutic agents.
Need for Further Study
My interests lie at the interface between physics, chemistry, and biology—both at the atomic level and at the systems level. This intersection is a major focus of current life-science research. Our work relies on a sophisticated technological and analytical infrastructure. As just one example, considerable research is still needed to refine both the precision and the accuracy of the various experimental and computational tools used to probe biomolecular processes with atomic resolution.
- Allosteric control of hemoglobin S fiber formation by oxygen and its relation to the pathophysiology of sickle cell disease.
- Henry ER, Cellmer T, Dunkelberger EB, Metaferia B, Hofrichter J, Li Q, Ostrowski D, Ghirlando R, Louis JM, Moutereau S, Galactéros F, Thein SL, Bartolucci P, Eaton WA.
- Proc Natl Acad Sci U S A (2020 Jun 30) 117:15018-15027. Abstract/Full Text
- Theoretical Simulation of Red Cell Sickling Upon Deoxygenation Based on the Physical Chemistry of Sickle Hemoglobin Fiber Formation.
- Dunkelberger EB, Metaferia B, Cellmer T, Henry ER.
- J Phys Chem B (2018 Dec 13) 122:11579-11590. Abstract/Full Text
Research in Plain Language
My lab studies how proteins alter their shapes. Long polypeptide chains make up proteins. We study how these chains fold to make a complex protein structure. We also examine how structural changes relate to the protein’s function. Some studies investigate the basic physical principles involved in the folding process. We also detect and measure changes in heme proteins. These proteins play a key role in binding oxygen to red blood cells. We identified the motions of atoms involved in protein changes. My lab has used time-resolved x-ray crystallography to visualize the motions of atoms directly.