Research in the Rienstra group aims to advance multidimensional solid-state NMR (SSNMR) methods for full structure determination and build upon the rapid progress of the discipline as a whole over the last decade. We have established infrastructure, developed new capabilities of pulse sequences and instrumentation, and integrated advances from our group and others to apply powerful magic-angle spinning (MAS) methods to major outstanding research problems in chemistry, biophysics and structural biology. Our broad-based research program has made significant contributions in both methodology and applications of modern SSNMR.
Our group is one of roughly a dozen laboratories worldwide with the capabilities to acquire and interpret multidimensional magic-angle spinning (MAS) spectra of uniformly-13C,15N-enriched solid proteins. Instrumental resources at UIUC are among the best currently available and include custom-designed 500, 600 (two) and 750 MHz SSNMR spectrometers with triple and quadruple resonance MAS probes. We have developed unique capabilities specific for studying membrane proteins at high magnetic fields, including new probe designs and pulse sequences, which are supported by novel sample preparation and data analysis technologies. We have made 2D SSNMR experiments routine, 3D experiments more powerful, and 4D magic-angle spinning (MAS) experiments in solid proteins possible for the first time. These experiments enable us to measure long-range internuclear distances (derived from dipolar couplings) and local dihedral angle restraints (derived from tensors) simultaneously at all amino acid residues in proteins. From these restraints, we calculate molecular structures with atomic coordinates and motions at sub-Angstrom precision, including the subtle effects of chemical modifications and non-covalent intermolecular interactions, such as small molecule binding. This information is essential both for fundamental understanding of protein structure and dynamics, as well as for practical applications such as rational drug design.
We apply these methods of physical chemistry to long-standing problems in structural biology. Proteins linked to disease phenotypes, including neurodegenerative diseases and circulatory disorders, are often found in membrane-associated or aggregated states, whose physicochemical properties impede examination by x-ray crystallography or solution NMR. Despite these challenging sample conditions, our techniques provide atomic-resolution insight into molecular structure under functional conditions. We envision a new generation of chemical biology, where fundamental insights into structure and dynamics will be determined in membrane proteins, enabling both discovery of totally new structures and well as hypothesis-directed investigations into previously inaccessible systems.
We are primarily interested in the following four biological systems:
Alpha-Synuclein | Membrane Proteins | Blood Coagulation | Amphotericin
For more details, check the research sub-category pages below or our publications page.