Our group aims to understand how protein structures encode specificity for their binding partners, particularly small organic molecules, and how flexibility surrounding the binding site contributes to specificity. Conversely, we analyze how ligand binding locks proteins into specific conformations, regulating their activity.
Our research involves developing and distributing new computational techniques for modeling protein flexibility and solvation, aligning and detecting similarity in ligand binding sites among non-homologous proteins, and performing high-throughput screening for ligand discovery in flexible proteins.
We collaborate with experimentalists on modeling protein structures and designing mutations, and predicting ligand binding and function for integral membrane proteins, including respiratory enzymes and G-protein-coupled receptors. We also study soluble lipid droplet proteins and lipid biosynthetic enzymes. A shared goal is objective pattern recognition of the interaction motifs that define the binding of steroidal ligands and other lipids and detergents to conserved sites on proteins, which can be used to design molecular mimics and proteins with novel specificity.