Jerome and Lorraine Aresty Chair and Distinguished Professor
Department of Molecular Biology & Biochemistry
CABM, Room 307
679 Hoes Lane
Piscataway, NJ 08854
Computational NMR, hybrid methods of structure analysis, structural bioinformatics, molecular recognition, allosteric aspects of proteins and protein complexes, drug design, cancer biology, structural biology of influenza virus
The general aim of our research is to use NMR spectroscopy as a tool for protein engineering and structural bioinformatics. We develop new methods for protein solution structure determination and apply these techniques to proteins of pharmaceutical or medical interest. The combined methods of site-directed mutagenesis, NMR spectroscopy, and conformational energy calculations are being used to (1) determine three dimensional structures of small proteins in solution, (2) determine the structures of protein-protein, protein-receptor, and protein-nucleic acid complexes, (3) characterize effects of amino acid substitutions on protein structure, stability, and dynamics, (4) direct efforts to design and engineer proteins and provide information for rational drug design, and (5) study the molecular mechanisms by which proteins fold into their biologically-active conformations. We are currently working on structure determination and refinement of several DNA-and RNA-binding proteins. We have recently determined solution structures of an IgG-binding domain of staphylococcal Protein A and of an RNA-binding protein from E.coli which is overproduced in response to cold shock (Cold Shock Protein A). We have characterized structural changes in these molecules which are required for binding to IgG proteins or to nucleic acids. Nuclear relaxation time measurements are used to characterize intramolecular motion in these small proteins. This research has important implications in the fields of protein physical chemistry, molecular design, receptor-ligand interactions, and oncogenesis. We are attempting to develop a general strategy for using structural analysis by NMR as a means of deciphering the biochemical functions of new genes identified in the human genome project.