Molecular recognition—the non-covalent association of one molecule with another—is one of the most important molecular processes in biology. Non-covalent association dictates the structure of proteins, the correct transcription and translation of the information encoded in DNA and RNA molecules, the specificity and rates of enzymatic catalysis (and thus the structure of metabolism), and the patterns of communication of different parts of the cell and between cells. The fundamental molecular driving forces involved in interactions between molecules have been enumerated (ionic, electrostatic, hydrophobic, etc.), but are not well understood. Building a fundamental understanding of these interactions, however, would facilitate rational ligand design—a subset of problems in drug design, protein crystallization—the bottleneck for characterizing protein structure by crystallography, and the engineering of novel biologically-inspired materials from aggregations of proteins.
Our group studies molecular recognition in the contexts of protein-ligand interactions, protein crystallization, and multivalent receptor-ligand association. We integrate tools of calorimetry and thermodynamic analysis, protein crystallography and structural analysis, capillary electrophoresis, and molecular modeling with the goal of building structure-function relationships that will help us to understand the molecular driving forces in molecular recognition. We are particularly interested in water and the hydrophobic effect, the relationship between protein surface chemistry and the interactions among proteins in their crystals, and the role of bivalency in biology and especially in the immune system.