Biochemistry

Xiaoqin Zou

Assistant Professor of Physics
Assistant Professor of Biochemistry

E-mail:zoux@missouri.edu

Office: 222D Dalton

Mail: Dalton Cardiovascular Research Center
134 Research Park Drive
University of Missouri
Columbia, MO 65211

Phone: 573-882-6045

Fax: 573-884-4232

Lab site: http://zoulab.dalton.missouri.edu/

Educational background

Research description

The molecular interactions that drive ligand-protein binding are a key to quantitatively understanding the basis of molecular recognition and to designing therapeutic interventions through rational drug design. Drug molecules usually act by binding to specific target proteins. Drug candidates that have high binding affinities can be identified by their geometric and chemical complementarity to the target in a process analogous to solving a "jigsaw puzzle", if the target structure is known. An energy model that can give rapid and accurate evaluation of the molecular interaction strength is thus essential for selecting plausible candidate compounds from a chemical database consisting of hundreds of thousands of molecules.

We are developing novel and efficient algorithms to calculate binding free energies for ligand-receptor complexes. The derived energy models will be applied to protein-substrate interactions, protein-protein interactions, and structure-based drug design. We are also developing new docking algorithms to account for protein flexibility. Methods used in our laboratory include computer modeling, simulation and graphics display.

A second line of research in the laboratory is quantitative studies on structure-function relationship of membrane proteins. We use our models to provide insights into the molecular mechanisms of the functions of the membrane proteins of interest from structural and energetic analysis, and to facilitate experimental design to identify important protein regions and their functional roles.

Selected publications

Sheng-You Huang, Diana Bolser, Hao-Yang Liu, Tzyh-Chang Hwang, and Xiaoqin Zou. Molecular modeling of the heterodimer of human CFTR’s nucleotide-binding domains using a protein-protein docking approach. Journal of Molecular Graphics and Modelling, 27: 822-828, 2009.

Sheng-You Huang, and Xiaoqin Zou. An iterative knowledge-based scoring function for protein-protein recognition. Proteins: Structure, Function and Bioinformatics 72: 557-79, 2008.

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: Parameterization of the generalized Born model and comparison with Poisson-Boltzmann approaches. Journal of Physical Chemistry B, 110, 9304-13, 2006.

Zhen Zhou, Xiaohui Wang, Hao-Yang Liu, Xiaoqin Zou, Min Li, and Tzyh-Chang Hwang. The two ATP binding sites of CFTR play distinct roles in gating kinetics and energetics. Journal of General Physiology 128: 413-22, 2006.