Protein – ligand interactions and protein-protein interactions are widespread critical processes in cellular functions and macromolecular assemblies. The ability to predict these interactions will have a far reaching impact on understanding the mechanisms of these important biological processes. A prominent application is rational design of drug molecules that can bind to the catalytic site of the target protein (e.g., in bacteria and cancer cells). Xiaoqin Zou’s research group works on physics-based modeling of protein-ligand and protein-protein interactions. The group’s ongoing research program includes the following projects: (1) Development of physical models to evaluate protein-ligand and protein-protein binding free energies. This requires accurate modeling of complex molecular interactions such as electrostatic interactions, van der Waals interactions, and entropic effects. (2) Structure-based inhibitor/drug design. For a given known protein (drug target), the group screens for chemical compounds that can form low-free energy complexes with the target protein. These compounds could become therapeutic drug candidates for clinical trials if they pass toxicity and metabolism tests. (3) Modeling structure-function relationship for membrane proteins. Membrane proteins play crucial structural and functional roles in cellular and physiological processes. Xiaoqin Zou also investigates the mechanisms of membrane protein functions from structural and thermodynamic analysis, and facilitate experimental design to enhance or degrade the membrane protein functions through mutagenesis or intervention of agents.

Featured story: Physics Theorist Looks for Better Ways to Treat Diseases