Hong Guo Assistant Professor, Department of Biochemistry, Cellular & Molecular Biology The University of Tennessee F205 Walters Life Sciences 1414 W. Cumberland Ave Knoxville, TN 37996 865-974-3610 hguo1@utk.edu

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Description of Research:
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.

Selected Publications:

• Guo H and Rao N (2005) Chorismate mutase-Catalyzed Claisen Rearrangement (Book Chapter) in Claisen Rearrangements, Udo Nubbemeyer and Martin Hiersemann, Eds., Wiley-VCH Verlag (in press).


• Guo H, 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. (in press).


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


• Xu Q and Guo H (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.


• Shi Q-S, Wang SQ, Zhu Y, Wei D-Q, Guo H, Sirois S and Chou K-C (2004) Polyprotein cleavage mechanism of SARS Co-C Mpro and chemical modification of the octapeptide. Peptides 25: 1857-1864.


• Guo H, Cui Q, Lipscomb WN and Karplus M (2003) Understanding the Role of Active Site Residues in Chorismate Mutase Catalysis from Molecular Dynamic Simulations. Angew. Chem. Int. Ed. 42: 1508-1511.


• Cui Q, Guo H and Karplus M (2002) Combining ab initio and density functional theories with semiempirical methods. J. Chem. Phys. 117: 5617.


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


• Guo H, Gresh N, Roques BP and Salahub DR (2000) Many-body effects in hydrogen-bonded peptide networks and their contributions to ligand binding. J. Phys. Chem. B 104: 9746.


• Gresh N, Guo H, Salahub DR, Roques BP and Kafafi SA (1999) Critical Role of Anisotropy for the Dimerization Energies of Two Protein-Protein Recognition Motifs. J. Am. Chem. Soc. 121: 7885.


• Guo H and Salahub DR (1998) Cooperative Hydrogen Bonding and Enzyme Catalysis. Angew. Chem. Int. Ed. Engl. 37: 2985-2990.


• MacKerell Jr. AD, Bashford D, Bellott M, Dunbrack Jr. RL, , Evanseck JD, Field MJ, Fischer S, Gao J, Guo H, Ha S, Joseph-McCarthy D, Kuchnir L, Kuczera K, Lau FTK, Mattos C, Michnick S, Ngo T, Nguyen DT, Prodhom B, Reiher III WE, Roux B, Schlenkrich M, Smith JC, Stote R, Straub J, Watanabe M, Wiórkiewicz-Kuczera J, Yin D, and Karplus M (1998) All-Atom Empirical Potential for Molecular Modeling and Dynamics Studies of Proteins. J. Phys. Chem. B 102: 3586-3616.