|PhD||University of California||San Diego, Calif.||Physics and Biophysics|
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.
Sheng-You Huang, Xiaoqin Zou. A non-redundant structure dataset for benchmarking protein-RNA computational docking. Journal of Computational Chemistry 34: 311-318, 2013.
Tao Yu, Xiao-Qing Wang, Jian-Ping Sang, Chun-Xu Pan, Xian-Wu Zou, Tsung-Yu Chen, Xiaoqin Zou. Influences of mutations on the electrostatic binding free energies of chloride ions in Escherichia coli ClC. Journal of Physical Chemistry B, 116, 6431-6438 (2012).
Sheng-You Huang, Xiaoqin Zou. Construction and test of ligand decoy sets using MDock: Community Structure-Activity Resource benchmarks for binding mode prediction. Journal of Chemical Information and Modeling, Special Issue on CSAR 2010 Scoring Exercise. 51:2107-2114 (2011).
Sheng-You Huang, Xiaoqin Zou. Scoring and lessons learned with the CSAR benchmark using an improved iterative knowledge-based scoring function. Journal of Chemical Information and Modeling, Special Issue on CSAR 2010 Scoring Exercise. 51:2097-2106 (2011).
Sheng-You Huang, Xiaoqin Zou. Statistical mechanics-based method to extract atomic distance-dependent potentials from protein structures. Proteins: Structure, Function and Bioinformatics, 79:2648–2661 (2011).
Sam Z. Grinter, Yayun Liang, Sheng-You Huang, Salman M. Hyder, Xiaoqin Zou. An inverse docking approach for identifying new potential anti-cancer targets. Journal of Molecular Graphics and Modelling, 29: 795-799 (2011).