Hong Guo, Ph.D.

Research Statement

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, mixed quantum mechanical/molecular mechanical (QM/MM) methods and other computational approaches to address the questions in these research areas. Several systems are currently under investigations in our laboratory, including protein lysine methyltransferases, RNA polymerases, serine-carboxyl peptidases, chorismate mutase, cytidine deaminase, and adenosine deaminase. We also study structural and dynamic features of proteins and try to understand the forces that stabilize proteins.

Selected Publications

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 β-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.

Q. Xu, H-B. Guo, A. Wlodawer and H. Guo* (2006) The Importance of Dynamics in Substrate-Assisted Catalysis and Specificity, J. Am. Chem. Soc, 128, 5994-95.

H-B. Guo, A. Wlodawer, T. Nakayama, Q. Xu, and H. Guo* (2006) On the Catalytic Role of Proton Transfers in The Formation of Tetrahedral Adduct in a Serine Carboxyl Peptidase, Biochemistry, 45, 9129-9137.

H. Guo* and N. Rao, (2006) Chorismate Mutase Catalyzed Claisen Rearrangement, in The Claisen Rearrangement, Nubbemeyer and Hiersemann (Eds.), Wiley-VCH, 1-21.

H. Guo* and H-B Guo (2006) Biological Basics for Protein Structures, in Computational Methods for Protein Structure Prediction and Modeling, Ying Xu, Dong Xu and Jie Liang (Eds), Springer, 229-239.

H-B. Guo, A. Wlodawer, and H. Guo* (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.

H-B. Guo, N., Rao, Q. Xu, and H. Guo* (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.

Q. Xu and H. Guo* (2004) “Quantum Mechanical/Molecular Mechanical Molecular-Dynamics Simulations of Cytidine Deaminase: from Stabilization of Transition-State Analogs to Catalytic Mechanisms” J. Phys. Chem. B, 108, 2477-2483.

H-B. Guo, R. Beahm, and H. Guo* (2004) “Stabilization and Destabilization of the Cα-H••O=C Hydrogen Bonds Involving Proline Residues in Helices” J. Phys. Chem. B, 108, 18053-18064.

H. Guo, Q. Cui, W.N. Lipscomb, and M. Karplus (2001) “Substrate conformational transitions in the active site of chorismate mutase”, Proc. Natl. Acad. Sci.  U.S.A., 98, 9032-9037.

Contact Information

Office:
Room F-223
Walters Life Sciences
Phone: (865) 974-3610

Lab:
Room C-204
Walters Life Sciences
Phone: (865) 974-3830

Email: hguo1@utk.edu