The essence of biological specificity resides in the energetics, dynamics and structural aspects of protein-ligand complexes. Although a great deal of emphasis has been placed upon elucidation of the structural aspects of proteins, primarily through the use of X-ray diffraction studies, the understanding of ligand binding and enzyme catalysis cannot proceed in the absence of knowledge of the energetics and dynamics of the systems. During the past decade diverse techniques such as NMR, hydrogen exchange and fluorescence spectroscopy have demonstrated that proteins are dynamic molecules. Theoretical treatments such as molecular dynamics calculations have also predicted motions of protein residues. A picture of the protein molecule has thus developed which is quite different from the rigid, static descriptions suggested by earlier X-ray diffraction studies. Considerable effort is now being focused on elucidating the functional significance of these motions to enzyme catalysis and the energetics of ligand binding. Dr. Jameson will examine ligand binding and subunit-subunit interactions in malate dehydrogenase, cytoplasmic malate dehydrogenase and elongation factor using fluorescence spectroscopy, elevated hydrostatic pressure and enzyme kinetic measurements. Fluorescence spectroscopy permits the determination of lifetimes as a function of environment and rotation dynamics of tryptophans in proteins. High pressure techniques are currently being applied with increasing frequency to the study of biological molecules because of the intrinsic advantages of the technique as compared to other techniques such as temperature variation.
