My research direction is to investigate mechanisms of enzyme-catalyzed reactions 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 for enzymes. 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 and mixed quantum mechanical/molecular mechanical (QM/MM) approaches to address the questions in these research areas. Several systems are currently under investigations in our laboratory, including chorismate mutase, cytidine deaminase, adenosine deaminase, and serine-carboxyl peptidases. We also study structural features of proteins and try to understand the forces that stabilize proteins.
- Ph.D., Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA
Chu, Y., Xu, Q and Hong Guo (2010) Understanding Energetic Origins of Product Specificity of SET8 from QM/MM Free Energy Simulations: What Causes the Stop of Methyl Addition during Histone Lysine Methylation? J. Chem. Theory Comput., 2010, 6, 1380-1389.
Xu, Q., Li, L-Y., and Guo, H. (2010) “Understanding the Mechanism of Deacylation Reaction Catalyzed by the Serine Carboxyl Peptidase Kumamolisin-As: Insights from QM/MM Free Energy Simulations” J. Phys. Chem. B, 114, 10594–10600.
Xu, Q., Ye, X., Li, L.-Y, Cheng, Z. M., and Hong Guo (2010) Structural Basis for the Action of Xyloglucan Endotransglycosylases/hydrolases: Insights from Homology Modeling. Interdiscip. Sci., 2010; 2: 133-139.
H. Guo* et al., QM/MM Analysis of the Catalytic Active Sites in Cellulases, in Computational Modeling in Lignocelluosic Biofuel Production, M. Nimlos and M.F. Crowley (Eds), ACS Publishing, invited contribution (Book Chapter), in revision.
Qin Xu, Xia Ye, (Max) Zong-Ming Cheng, and Hong Guo*, Structural Basis for the Action of Xyloglucan Endotransglycosylases/hydrolases: Insights from Homology Modeling, Interdisciplinary Sciences-- Computational Life Sciences, in revision.
Qin Xu, Yuzhuo Chu, Hao-Bo Guo, Jeremy C. Smith, and Hong Guo*, Energy Triplets for Writing Epigenetic Marks: Insights from QM/MM Free Energy Simulations of Protein Lysine Methyltransferases, Chemistry, a European Journal, in press.
Jerry M. Parks, Hong Guo, Cory Momany, Liyuan Liang, Susan M. Miller, Anne O. Summers,and Jeremy C. Smith, Mechanism of Hg-C Protonolysis in the Organomercurial Lyase MerB, J. Am. Chem. Soc., in press.
H-B. Guo, A. Gorin, and H. Guo*, A Peptide-Linkage Deletion Procedure for Estimate of Energetic Contributions of Individual Peptide Groups in a Complex Environment: Application to Parallel ß-Sheets, Interdisciplinary Sciences-- Computational Life Sciences, 2009, 1, 12-20.
H-B Guo and H. Guo* (2007) Mechanism of Histone Methylation Catalyzed by Protein Lysine Methyltransferase SET7/9 and Origin of Product Specificity, Proc. Natl. Acad. Sci. U.S.A., 104, 8797-8802.
Q. Xu, H-B Guo, A. Wlodawer, T. Nakayama, and H. Guo* (2007) The QM/MM Molecular Dynamics and Free Energy Simulations of the Acylation Process Catalyzed by the Serine Carboxyl Peptidase Kumamolisin-As, Biochemistry, 46, 3784-3792.
Q. Xu, H-B Guo, A. Gorin, and H. Guo* (2007) Stabilization of a Transition-State Analogue at the Active Site of Yeast Cytosine Deaminase: Importance of Proton Transfers, J. Phys. Chem. B, 111, 6501-6506.