Our work is centered on studying the structural and dynamical properties of proteins in order to understand the molecular mechanisms of protein function. We have developed new spectroscopic methods to obtain the vibrational spectra of specific protein groups and/or bound ligands, even within large proteins. With these techniques, it is possible to determine bond lengths with an accuracy of better than 0.01 Å. We also have developed techniques to monitor atomic motion in proteins on multiple time scales, as fast as picoseconds and out to minutes.
The primary problem of the lab is to understand the dynamics of enzymatic catalysis at a molecular level. This involves measurement of (1) static structures of enzymes complexes with their ligands and (2) how atomic motion evolves during the catalytic event. Structure is probed with vibrational spectroscopic tools that are capable of determining the Raman and IR spectra of bound substrates and specific protein molecular moieties. Vibrational spectroscopy yields a very high resolution of structure (better than 0.01 Å), and changes on this order are key to understanding enzymatic catalysis. The lab develops and applies advanced spectroscopic techniques as well as computational methods to understand how protein structure and dynamics determines function in proteins. We have worked extensively on several enzyme proteins. The idea is to understand the physics of atomic motion in proteins with a view that a deep understanding would lead to new classes of pharmaceuticals. The dynamics of protein folding is also an active area of study, that is how do proteins fold up into their functional three dimensional shapes. In fact the late dynamics of the protein folding problem is closely related to the dynamical nature of folded proteins.
We also wish to understand how proteins arrive at their three dimensional structure (the protein folding problem). A number of studies are underway to understand the thermodynamics of folding. In addition, the crucial kinetic events of protein folding occur faster than the conventional millisecond time scale of stopped-flow mixing techniques. The early kinetic events (down to nanoseconds) in the folding process are being studied using advanced techniques that initiation chemistry on fast time scales.