Education and Biography

Ph.D., Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA

Research Interests

My research focuses on application and development of computational approaches to understand biological structure and function. One of our research directions is to investigate catalytic mechanisms and specificity/promiscuity of enzymes and inhibitor binding processes by use of state-of-the art computational approaches. We are interested in understanding the origin of high catalytic efficiency and selectivity/promiscuity of enzyme-catalyzed reactions. These studies would, in addition to being of fundamental scientific importance, also improve the basis for designing inhibitors, efficient drugs and enzyme mimics. We use molecular dynamics (MD) simulations, free energy calculations, mixed quantum mechanical/molecular mechanical (QM/MM) methods and some other computational approaches to address questions in this research area. Several enzyme systems are currently under investigations in our laboratory. Another direction of our research is to integrate structural information (such as 3-dimensional protein models) with other datasets for understanding the enzymatic and regulatory pathways required for Crassulacean Acid Metabolism (CAM) of plants, which provides an excellent opportunity to engineer enhanced photosynthetic performance and water use efficiency (WUE) into bioenergy crops. We also study structural and dynamic features of proteins and try to understand the forces that that stabilize proteins.

Home page: http://www.bio.utk.ed/guo/

Selected Publications

• Yue, Y. and Guo, H. (2014) Quantum Mechanical/Molecular Mechanical Study of Catalytic Mechanism and Role of Key Residues in Methylation Reactions Catalyzed by Dimethylxanthine Methyltransferase in Caffeine Biosynthesis. J. Chem. Inf. Model., 54, 593–600.

• Lian, P.,  Guo, H-B, Smith, J. C., Wei, D. Q., and Guo, H. (2014) Catalytic mechanism and origin of high activity of cellulase TmCel12A at high temperature: a quantum mechanical/molecular mechanical study. Cellulose, 21, 937–949.

• Yao, J., Wlodawer, A., and Guo, H. (2013) Understanding the Autocatalytic Process of Pro-kumamolisin Activation from Molecular Dynamics and Quantum Mechanical/Molecular Mechanical (QM/MM) Free-Energy Simulations. Chem. –  Eur. J., 19, 10849–10852.

• Chu, Y-Z., Yao, J., and Guo, H. (2012) Understanding the Product Specificity of G9a-Like Protein (GLP) and Effects of Mutations from QM/MM MD and Free Energy Simulations. PLosONE, 7, e37674.

• Yao, J., Xu, Q., Chen, F., and Guo, H. (2011) QM/MM Free Energy Simulations of Salicylic Acid Methyltransferase: Effects of Stabilization of TS-like Structures on Substrate Specificity. J. Phys. Chem. B, 115, 389–396.

• Xu, Q., Chu, Y-Z., Guo, H-B., Smith, J. C.,and Guo, H. (2009) Energy Triplets for Writing Epigenetic Marks: Insights from QM/MM Free-Energy Simulations of Protein Lysine Methyltransferases” Chem. –  Eur. J.,  15, 12596–12599.