Hong Guo, Ph.D.
My research focuses on application and development of computational approaches to understand biological structure and function. Our main research direction is to investigate catalytic mechanisms and specificity 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 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 the questions in these research areas. Several enzyme systems are currently under investigations in our laboratory, including AdoMet-dependent methyltransferases from different enzyme families, serine-carboxyl peptidases, cellulases and mercuric ion reductase. We also study structural and dynamic features of proteins and try to understand the forces that stabilize proteins.
Chu, Y-Z., Li, G-H., and Guo, H. (2013) QM/MM MD and Free Energy Simulations of the Methylation Reactions Catalyzed by Protein Arginine Methyltransferase PRMT3. Can. J. Chem. (in press).
Chu, Y-Z., Yao, J-Z., 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-Z, Chu, Y-Z, An, R., and Guo, H. (2012) Understanding Product Specificity of Protein Lysine Methyltransferases from QM/MM Molecular Dynamics and Free Energy Simulations: The Effects of Mutation on SET7/9 beyond the Tyr/Phe Switch. J. Chem. Inf. and Model., 52, 449−456.
Xu, Q., Yao, J-Z., Wlodawer, A., and Guo, H. (2011) Clarification of the Mechanism of Acylation Reaction and Origin of Substrate Specificity of the Serine-Carboxyl Peptidase Sedolisin through QM/MM Free Energy Simulations. J. Phys. Chem. B, 115, 2470-2476.
Yao, J-Z., 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., 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.
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.
Saharay, M., Guo, H-B., Smith, J. C., and Guo, H. (2010) QM/MM Analysis of Cellulase Active Sites and Actions of the Enzymes on Substrates in Computational Modeling in Lignocellulosic Biofuel Production. Editor(s): Mark R. Nimlos and Michael F. Crowley. ACS Symposium Series, Volume 1052, Chapter 7, Page 135-154.
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. Chemistry, a European Journal, 15, 12596–12599.
Guo, H-B., Gorin, A., and Guo, H. (2009) A Peptide-Linkage Deletion Procedure for Estimate of Energetic Contributions of Individual Peptide Groups in a Complex Environment: Application to Parallel β-Sheets. Interdisciplinary Sciences-- Computational Life Sciences, 1, 12-20.
Guo, H-B. and Guo, H. (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.
Xu, Q., Guo, H-B., Wlodawer, A., Nakayama, T., and Guo, H. (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.
Xu, Q., Guo, H-B., Wlodawer, A., and Guo, H. (2006) The Importance of Dynamics in Substrate-Assisted Catalysis and Specificity. J. Am. Chem. Soc, 128, 5994-95.
Guo, H-B., Wlodawer, A., Nakayama, T., Xu, Q., and Guo, H. (2006) On the Catalytic Role of Proton Transfers in The Formation of Tetrahedral Adduct in a Serine Carboxyl Peptidase. Biochemistry. 45, 9129-9137.
Guo, H. and Rao, N. (2006) Chorismate Mutase Catalyzed Claisen Rearrangement in The Claisen Rearrangement, Nubbemeyer and Hiersemann (Eds.), Wiley-VCH, 1-21.
Guo, H-B., Wlodawer, A., and Guo, H. (2005) A General Acid-Base Mechanism for the Stabilization of a Tetrahedral Adduct in a Serine-Carboxyl Peptidase: A Computational Study. J. Am. Chem. Soc., 127, 15662-15663.
Guo, H-B., Rao, N., Xu, Q., and Guo, H. (2005) Origin of Tight Binding of a Near-Perfect Transition-State Analog by Cytidine Deaminase: Implications for Enzyme Catalysis. J. Am. Chem. Soc., 127, 3191-3197.
Guo, H-B., Beahm, R., and Guo, H. (2004) Stabilization and Destabilization of the Cα-H••O=C Hydrogen Bonds Involving Proline Residues in Helices. J. Phys. Chem. B, 108, 18053-18064
Walters Life Sciences
Phone: (865) 974-3610
Walters Life Sciences
Phone: (865) 974-3830