Protein - small molecule (ligand) interactions, protein-protein interactions, rational inhibitor/drug design, and modeling of quantitative structure-function relationships of membrane proteins.

 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).

 My research group works on physics-based modeling of protein-ligand and protein-protein interactions. Our 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), we screen 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. We investigate 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.

Selected Publications

Sheng-You Huang, and Xiaoqin Zou. Ensemble docking of multiple protein structures: Considering protein structure variations in molecular docking. Proteins: Structure, Function and Bioinformatics, 66, 399-421, 2007.

Sheng-You Huang, and Xiaoqin Zou. Efficient molecular docking of NMR structures: Application to HIV-1 protease. Protein Science, 16, 43-51, 2007.

 Sheng-You Huang, and Xiaoqin Zou. An iterative knowledge-based scoring function to predict protein-ligand interactions: I. Derivation of the interaction potentials. Journal of Computational Chemistry, 27, 1866-75, 2006.

Sheng-You Huang, and Xiaoqin Zou. An iterative knowledge-based scoring function to predict protein-ligand interactions: II. Validation of the scoring function. Journal of Computational Chemistry 27, 1876-82, 2006.

Hao-Yang Liu, and Xiaoqin Zou. Electrostatics of ligand binding: Parametrization of the generalized Born model and comparison with Poisson-Boltzmann approaches. Journal of Physical Chemistry B 110, 9304-13, 2006.

Hao-Yang Liu, Irwin D. Kuntz, and Xiaoqin Zou. Pairwised GB/SA scoring function for structure-based drug design. Journal of Physical Chemistry B 108, 5453-62, 2004.

Xiaoqin Zou, Yaxiong Sun, and Irwin D. Kuntz. Inclusion of solvation in ligand binding free energy calculations using generalized-Born model. Journal of American Chemical Society 121: 8033-43, 1999.