BERNARD D. SANTARSIERO

I am a Research Professor in the Department of Pharmaceutical Sciences in the College of Pharmacy. My research interests focus on the development and use of computational, biochemical, and spectroscopic methods, especially x-ray diffraction, for the detailed characterization of molecules at atomic resolution. This approach is used to investigate the fundamental structural, functional, and energetic differences of chemical reactivity in chemical, biological, and material systems. We routinely use both monochromatic and polychromatic, time-resolved diffraction methods on single crystals, and have recently extended our studies to powders and solutions.

Examples of our research include the study of enzyme targets to develop new and novel antibiotics, treat neurodegenerative diseases, investigate basic processes in cell division, bacterial cell signaling, or protein-protein interactions, or develop new candidates for biomass energy production.

The structural studies of enzyme targets, enzyme mutants, and their enzyme-ligand complexes leads to a detailed view of the active site, and provides key information to develop substrate, product, or transition-state analogues as potential inhibitors, and provides an opportunity to block essential metabolic pathways in an infectious organism. In addition, allosteric binding sites can be identified through high-throughput screening; they also affect substrate binding, product release, and overall protein conformational flexibility during catalysis, and reveal a more complete view of the enzymatic event.

High-throughput chemical compound library screening, and a detailed dynamic view of the catalytic landscape of an enzyme's function, coupled with the characterization of new compound scaffolds from natural product sources, provides a rich basis for discovering new and effective pharmaceutical drugs to improve human health.