Our group's research focuses on small molecule and protein design as an approach to understanding macromolecule structure and function. One primary research interest is in the de novo design, in which one designs proteins beginning from first principles. This approach critically tests our understanding of protein folding and function, while also laying the groundwork for the design of proteins and biomimetic polymers with properties unprecedented in nature. The de novo design of proteins has proven to be a useful approach for understanding the features in a protein sequence that cause them to fold into their unique three-dimensional structures. In addition, it has been possible to design functionally interesting proteins, which bind redox-active cofactors, DNA, and transition metals. Finally, this approach has been extended to the design of membrane-active proteins, including ion channels, antibiotics and fusogenic agents.
We also study the structure and function of a number of pharmacologically interesting systems. Our group is determining the structure of the M2 proton channel from influenza A virus, and its mode of inhibition by various channel-blocking drugs. In collaboration with Joel Bennett (Department of Medicine), we study the mechanism of signal transduction of integrins such as ?II?b3, with a particular focus on the role played by the membrane-spanning regions of this protein. We have developed small molecule mimics of integrins and the platelet collagen receptor, gpVI. Finally, our group developed a number of small molecule mimics of antimicrobial host defense proteins, which show considerable promise for treating antibiotic-resistant infections.