Research
NMR Crystallography in Enzyme Active Sites
Our group is pioneering the development and application of NMR crystallography – the synergistic combination of solid-state NMR, X-ray crystallography, and computational chemistry – to enzyme active sites, where it provides atomic-resolution characterization of stable intermediates as well as species near transitions states. Enabling this is the ability to measure active-site isotropic and anisotropic NMR chemical shifts under conditions of active catalysis, and the development of fully quantum mechanical computational models of the enzyme active site that allow the accurate prediction of NMR spectral parameters.
SSNMR Methods
Resonance assignments are an essential first step in structural studies with NMR. Our group is developing high-resolution and high-sensitivity correlation spectroscopy for organic and biological solids. We have introduced multiple techniques to assign through-bond connectivity in complex organic solids, effect 13C-13C correlation at natural abundance isotope levels, and obtain 2D and 3D correlation spectra with substantially increased spectral resolution in biological solids as large as 143 kDa.
Dynamic NMR
NMR has proven to be an excellent tool for the characterization of dynamics on chemically important time scales, and it does so without the need to perturb equilibrium. Our group has focused on the application of dynamic NMR to molecules raging in size from small molecules in solution, such as the pyridine carboxamides, to larger biomolecules, including proteins, DNA, and carbohydrates.
Theory and Pedagogy
Tensors and Rotations in NMR: The transformation of second-rank Cartesian tensors under rotation plays a fundamental role in the theoretical description of nuclear magnetic resonance experiments, providing the framework for describing anisotropic phenomena such as single crystal rotation patterns, tensor powder patterns, sideband intensities under magic angle sample spinning, and as input for relaxation theory. In our contribution to Concepts in Magnetic Resonance (38A(5), 221-235 (2011)), we reviewed the transformation of second-rank tensors in Cartesian and spherical forms and showed how the discrepancies in their sense of rotation could be reconciled. The result is a uniform and consistent approach to the rotation of the physical system and the corresponding transformation of the spatial components of the NMR Hamiltonian, expressed as either Cartesian or spherical tensors.