个人简介

B.Sc. (UTSC); Ph.D. (UNC-Chapel Hill)

研究领域

Physical Chemistry, Chemical biology and biochemistry

Mechanistic simulation of enzyme catalysis; Protein structure, dynamics, and recognition; Multi-scale computer simulation of biomolecular processes; Molecular design. Dr. Hu's research programmes: 1. Mechanistic simulation of enzyme catalysis Enzymes play critical roles in life processes by catalyzing vastly diverse chemical reactions, ranging from simple carbon dioxide hydration to complicated long-range electron / radical transfer and photochemical process. Compared with uncatalyzed processes, enzymes can significantly speed up the reactions. Origin of the catalytic power of enzymes constitutes an intellectual challenge to our understanding of nature; the knowledge of which would immediately contribute to biomedicinal research such as drug design. Development of efficient simulation methods for accurate modeling of enzyme catalysis is our focal point, which requires research in both quantum mechanical computation methods and statistical phase-space sampling techniques. 2. Protein structure, dynamics and recognition Although the functions of protein molecules are ultimately determined by the primary sequences, the thermodynamics and kinetics of the functioning process are direct results of the interplay between protein structure and dynamics. A complete picture of the energy landscape of protein molecule is the key to the understanding of protein functions. We are interested in the correlation between protein structure and dynamics, in particular how this correlation was shaped by the functioning requirement in the thermodynamic evolution process. Understanding the hierarchic organization of protein function and dynamics, in both temporal and chemical spaces, is our final goal. 3. Multi-scale computer simulation of biomolecular processes Many important biomolecular processes are participated by multiple protein/DNA/ RNA molecules and span long timescales. We are interested in developing multi-scale computer simulations to reveal the molecular details of these processes. 4. Molecular design This project applies aforementioned computational methods to the design of new molecules for medicinal or economic significance. The questions we like to explore are: (1) Based on the atomistic and even electronic information available for the transition state of an enzyme-catalyzed reaction, can we design new and effective inhibitors? (2) Can we design a new enzyme bottom-up from a desired reaction mechanism?

近期论文

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H. Hu*, A. Boone and W.T. Yang (2008) Mechanism of OMP decarboxylation in orotidine 5'-monophosphate decarboxylase. J. Am. Chem. Soc. in print H. Hu and W.T. Yang (2008) Free energies of chemical reactions in solution and in enzymes with ab initio QM/MM methods. Annu. Rev. Phys. Chem. 59:573-601 X.C. Zeng, H. Hu, X.Q. Hu, A.J. Cohen, and W.T. Yang (2008) QM/MM calculation of electron transfer process with a fractional number of electrons approach. J. Chem. Phys. 128:124510 H. Hu, Z.Y. Lu, J.M. Parks, S.K. Burger and W.T. Yang (2008) Quantum mechanics/ molecular mechanics minimum free- energy path for accurate reaction energetics in solution and enzymes: Sequential sampling and optimization on the potential of mean force surface. J. Chem. Phys. 128:034105 H. Hu*, Z.Y. Lu, M. Elstner, J. Hermans and W.T. Yang (2007) Simulating water with the SCC-DFTB method: From molecular clusters to the liquid state. J. Phys. Chem. A 111:5685-5691 H. Hu, Z.Y. Lu and W.T. Yang (2007) Fitting molecular electrostatic potentials from quantum mechanical calculations. J. Chem. Theory Comput. 3:1004-1013 (20 most-accessed articles) H. Hu, Z.Y. Lu and W.T. Yang, (2007) QM/MM Minimum Free Energy Path: Methodology and application to triosephosphate isomerase, J. Chem. Theory Comput. 3:390- 406 (20 most-accessed articles) H. Hu, J. Hermans and A.L. Lee (2005) Relating side-chain mobility in proteins to rotameric transitions: Insights from molecular dynamics simulations and NMR. J. Biol. NMR 32:151-162 H. Hu and W. Yang (2005) Dual-topology-dual-coordinate free energy simulation using QM/MM force field. J. Chem. Phys. 123:41102 H. Hu, M.W. Clarkson, J. Hermans and A.L. Lee (2003) Increased rigidity of eglin c at acidic pH: Evidence from NMR spin relaxation and MD simulation. Biochemistry 42:13856- 13868 H. Hu, M. Elstner and J. Hermans (2003) Comparison of a QM/MM force field and molecular mechanics force fields in simulations of alanine and glycine "dipeptides" (Ace-Ala- Nme and Ace-Gly-Nme) in water in relation to the problem of modeling the unfolded peptide backbone in solution. Proteins: Struct, Funct. & Genet. 50:451-463 H. Hu, R.-H. Yun and J. Hermans (2002) Reversibility of free energy simulations: Slow growth may have a unique advantage (With a note on the use of Ewald summation). Mol. Simulation 28:67-80