- Ph. D., Dept. of Chem. & Chem. Biol., Harvard University (Advisor: Martin Karplus)
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/adenosine deaminase, merB and merA. We also study structural and dynamic features of proteins and try to understand the forces that stabilize proteins.
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. 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 (in press).
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. Wlodawer, and H. Guo* (2006) “The Importance of Dynamics in Substrate-Assisted Catalysis and Specificity”, J. Am. Chem. Soc., 128, 5994-5995.
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 (Book Chapter).
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.