Intermolecular Forces, Recognition, and Dynamics

Our laboratory focuses on elucidating the coupling of the forces, structure, and dynamics of biologically important macromolecules. The next challenge in structural biology is to understand the physics of interactions between molecules in aqueous solution. The ability to take advantage of the increasing number of protein and nucleic acid structures determined by x-ray crystallography and solution NMR will depend critically on this knowledge to understand the strength and specificity of interactions among biologically important macromolecules that control cellular function and to design rationally agents that can effectively compete with those specific interactions associated with disease. Our research program can be broadly divided into two areas. We use direct force measurements to probe the interactions between biological macromolecules. In order to investigate the role of water in the interaction of individual molecules, we also measure and correlate changes in binding energies and in hydration accompanying specific recognition reactions of biologically important macromolecules in dilute solution, particularly of sequence specific DNA-protein complexes.