 Associate Professor
B.S. 1993, University of Science and Technology of China (USTC), P.R. China
Ph.D. 1997, Emory University
Postdoc, 1998-2001, Harvard University
Room: 8305i
Phone: 608-262-9801
Email: cui@chem.wisc.edu
Position: Associate Professor
Amino acids with an intermolecular proton bond as the proton storage site in bacteriorhodopsin, P. Phatak, N. Ghosh, H. Yu, Q. Cui and M. Elstner, Proc. Natl. Acad. Sci. USA, 105, 19672-19677 (2008) Proton transfer in Carbonic Anhydrase is controlled by electrostatics rather than the orientation of the acceptor, D. Riccardi, P. Konig, H. Guo and Q. Cui, Biochem., 47, 2369-2378 (2008) Gating Mechanisms of Mechanosensitive Channels of Large Conductance Part II: Systematic Study of Conformational Transitions, Y. Tang, J. Yoo, A. Yethiraj, Q. Cui and X. Chen, Biophys. J., 95, 581-596 (2008) (Cover) pKa of residue 66 in Staphylococal nuclease: insights from QM/MM simulations with conventional sampling, N. Ghosh, Q. Cui, J. Phys. Chem. B, 112, 8387-8397 (2008) (Cover) Extensive conformational changes are required to turn on ATP hydrolysis in myosin, Y. Yang, H. Yu and Q. Cui, J. Mol. Biol., 381, 1407-1420 (2008) Mechanochemical coupling in myosin motor domain, II. Analysis of critical residues, H. Yu, L. Ma, Y. Yang and Q. Cui, PLoS Comput. Biol., 3, 0214 (2007) The activation mechanism of a signaling protein at atomic resolution from advanced computations, L. Ma, Q. Cui, J. Am. Chem. Soc., 129, 10261-10268 (2007) Improving the Self-Consistent-Charge Tight-Binding-Density-Functional method for proton affinities and hydrogen bonding interactions, Y. Yang, H. Yu, D. York, Q. Cui, M. Elstner, J. Phys. Chem. A, 111, 10861-10873 (2007) Development of effective quantum mechanical/molecular mechanical (QM/MM) methods for complex biological processes, D. Riccardi, P. Schaefer, Y. Yang, H. Yu, N. Ghosh, X. Prat-Resina, P. Konig, G. Li, D. Xu, H. Guo, M. Elstner, and Q. Cui, J. Phys. Chem. B Feature Article, 110, 6458-6469 (2006) (Cover) "Proton holes" in long-range proton transfer reactions in solution and enzymes: A theoretical analysis, D. Riccardi, P. K"onig, X. Prat-Resina, H. Yu, M. Elstner, T. Frauenheim, Q. Cui, J. Am. Chem. Soc., 128, 16302-16311 (2006) Analysis of the functional motions in "Brownian molecular machines" with an efficient block normal mode approach, G. Li, Q. Cui*, Biophys. J. 86 , 743-763 (2004) Mechanochemical coupling in myosin: A theoretical analysis of ATP hydrolysis with molecular dynamics and combined QM/MM reaction path calculations, G. Li, Q. Cui*, J. Phys. Chem. B 108 , 3342-3357 (2004) The importance of van der Waals interactions in QM/MM simulations, D. Riccardi, G. Li, Q. Cui*, J. Phys. Chem. B 108 , 6467-6478 (2004) QM/MM Studies of Enzyme Catalyzed Dechlorination of 4-Chlorobenzoyl-CoA and Their Implications to Kinetic Model, D. Xu, Y. Wei, J. Wu, D. Dunaway-Mariano and H. Guo, Q. Cui, J. Gao, J. Am. Chem. Soc . 126, 13649-13658 (2004) What is so special about Arg 55 in the catalysis of cyclophilin A? Insights from hybrid QM/MM simulations, G. Li, Q. Cui*, J. Am. Chem. Soc . 125 , 15028 (2003) Free energy perturbation calculations with combined QM/MM potentials " complications, simplifications and applications to redox potential calculations, G. Li, X. Zhang, Q. Cui*, J. Phys. Chem. B 107 , 8643 (2003) What is so special about Arg 55 in the catalysis of cyclophilin A? Insights from hybrid QM/MM simulations, G. Li, Q. Cui*, J. Am. Chem. Soc . 125 , 15028 (2003) pKa calculations with QM/MM free energy perturbations, G. Li, Q. Cui*, J. Phys. Chem. B 107 , 14521 (2003) Combining implicit solvation model with hybrid QM/MM methods. A critical test with glycine, Q. Cui*, J. Chem. Phys . 117 , 4720 (2002) The functional specificities of Methylglyoxal Synthase (MGS) and Triosephopshate Isomerase (TIM): A combined QM/MM analysis, X. Zhang, D. H. T. Harrison, Q. Cui*, J. Am. Chem. Soc . 124 , 14871 (2002)
| Research Description
Understanding complex molecular systems using experiments alone is difficult. Computer simulations based on physical and chemical principles can complement experiments and provide novel insights into the behavior of these systems at an atomic level. Our research targets the development and applications of state-of-the-art computational tools that explore the underlying mechanisms of complex molecular systems. Enzymes and other biological macromolecules, along with bio-inorganic ligands, are of primary interest.
Simulation of complex molecular machines in bio-energy transduction:Biological systems involve many fascinating "molecular machines" that transform energy from one form to the other. Important examples are F1-ATP synthase and calcium pump, the former utilizes the proton motive force to synthesize ATP, while the latter employs the free energy of ATP binding and hydrolysis to transport calcium ions across the membrane. With the recent developments in crystallography, cyro-EM and single molecule spectroscopy, the working mechanisms of these nano-machines are being discovered. In order to understand the energy transduction process at an atomic level, our group is developing and applying state-of-the-art computational techniques to analyze the detailed mechanisms of several large molecular complexes including: myosin, RNA polymerase and the calcium pump. Questions of major interest include: (i). What are the functionally relevant conformational flexibilities of these complexes? (ii). How are the chemical events (e.g., ATP binding and hydrolysis) coupled to the mechanical (e.g., conformational transition) process? (iii). How is the efficiency for energy transduction regulated?
Understanding the catalytic mechanism of enzymes:Enzymes overshadow most chemical catalysts because they are extremely efficient and highly reaction-specific. Our group is developing and applying novel computational methods to explore the physical and chemical mechanisms behind the catalytic efficiency and specificity of several fascinating enzymatic systems. These include enzymes that exploit transition metal ions (copper chaperones), electronically excited states (aequorin), and radical intermediates (cholesterol oxidase). In addition to their important biological implications, an underlying theme for these systems is catalysis modulated by protein motion. Our studies will not only provide insights into the fundamental working mechanisms of enzymes, but may also lead to the rational design of enzymes (methyl glyoxal synthase, polyketide synthase) with improved or even altered functions.
Developing computational techniques and theoretical models for complex systems:A substantial amount of research activity in our group is geared toward developing novel computational techniques to make the simulation of complex biomolecular systems possible. One major area involves improving the efficiency and accuracy of combined quantum mechanical and classical mechanical methods, such that bond-breaking and bond-formation (chemistry!) can be studied in detail for realistic biological environments. Another area is related to the development of coarse-grained normal mode and molecular dynamics approaches, such that insights into the thermodynamics and kinetics of long time-scale processes (e.g., large-scale conformational transitions) can be obtained computationally. Finally, phenomenological models will also be developed to make connections between microscopic MD simulations (e.g., potential of mean force) and macroscopic observables (e.g., calcium flux across the membrane).
Interfacing biology and material science:The last decade has seen the thrilling developments in the science of materials at the nanometer scale. Nano-materials with tailored electrical, optical or mechanical properties have been synthesized. An exciting direction that has been recently recognized is that biomolecules can be used to provide control in organizing technologically important (non-biological) objects into functional nano-materials. The interaction between biomolecules and inorganic materials is fundamental to these applications, and we are using computational techniques to investigate this aspect. These studies are expected to play a guiding role in the design of novel hybrid materials and new sensors for biological molecules.
Last updated: October 3, 2003.
Alfred P. Sloan Research Fellowship (2004) CAREER Award, National Science Foundation (2004) Research Innovation Award, Research Corporation, 2003 Graduate student fellowship, Phillips Petroleum Co., 1994 - 1997 Lester Award, Emory University, 1996 Osborn R. Quayle Award, Emory University (1995)
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