Research in the Structural and Biophysical Chemistry group focuses on understanding the structure-function relationship of interactions between biological macromolecules of medical interest and their binding partners, with an emphasis on characterizing protein-protein and protein-ligand interactions. We support projects related to the Emeryville-based Infectious Diseases area as well as global projects in other disease areas, such as oncology, in collaboration with other NIBR sites.
To study protein-ligand interactions, our lab employs solution-state biomolecular NMR as a major technique, as well as additional structural and biophysical methods established in our group such as X-ray crystallography, SPR, DSF, BLI, and light scattering. Our goal is to understand molecular recognition and ‘druggability’ at a structural level to address critical biological questions in disease. This information allows us to modulate the target function using structure-based drug design. To support drug discovery projects, we focus on hit finding, hit validation, and structural characterization, primarily in the context of fragment-based lead discovery. Besides applying and improving established ligand- and protein-observed NMR methods, we are actively involved in developing new methods and tools, e.g., expanding the application of fluorine NMR in compound screening, automated data analysis, and utilizing sparse NMR-derived structural information to define protein-ligand binding modes.