Our laboratory is primarily interested in the mechanisms
of protein folding and the role these mechanisms play
in biological function. We use nuclear magnetic resonance
(NMR) and other types of spectroscopy to study the
solution structure, stability and folding reactions
of simple protein models. These include monomeric
lambda repressor, the B domain of protein A, RNase
P protein, and the RGS domains of several G protein
regulators. Our efforts are directed at measuring
the folding the kinetics and thermodynamics of these
systems, particularly under conditions relevant for
function. For example, our studies of RNase P (conducted
by MBP trainee Chris Henkels) indicate that the protein
folds only when it binds anion ligands. Our mechanistic
work aims to illuminate the key steps in ribonucleoprotein
assembly of the RNase P ribozyme. We are also interested
in the dynamic properties of native proteins in solution.
We study the motions of proteins over the picosecond
to millisecond time scale using a variety of NMR-based
experiments including N-15 relaxation studies, amide
hydrogen exchange rates and dynamic NMR. With these
results we hope to gain a better understanding of
the dynamic behavior of proteins in solution and the
role of these dynamics in function.
