Dr. Chang-Guo Zhan
Dr. Chang-Guo Zhan


Chang-Guo Zhan received a Ph.D. in Chemistry (Physical Chemistry) from University of Notre Dame and a Ph.D. in Science (Molecular Physics) from Institute for Molecular Science (IMS), Japan (Graduate University of Advanced Studies). Dr. Chang-Guo Zhan performed his postdoctoral research as a Postdoctoral Research Scientist at Department of Medicine, Columbia University. After that, he served as Associate Research Scientist at Department of Medicine, Columbia University and a Visiting Scientist at Pacific Northwest National Laboratory at the same time. Dr. Zhan joined the UK College of Pharmacy faculty as Associate Professor in July 1st, 2003 and was promoted to Professor in July 1st, 2007. He was elected as Fellow of American Association of Pharmaceutical Scientists (AAPS) in 2010. Dr. Zhan’s main research interest is drug design and discovery through integrated computational-experimental studies. Drugs designed and discovered in Dr. Zhan’s lab are either small molecules (as inhibitors of enzymes or agonists/antagonists of receptor proteins or DNA-binding molecules etc.) or engineered proteins (mutants with significantly improved biological functions and/or increased circulation time in the body). In order to rationally design a drug, Dr. Zhan’s lab may perform whatever types of molecular modeling (including homology modeling and molecular docking), simulations (e.g. MD and Monte Carlo), calculations (e.g. QM, QM/MM, MM-PBSA, QM/MM-PBSA, FEP, and QM/MM-FEP etc.), statistical analysis (including QSAR and Artificial Neural Network), and molecular design (automated virtual screening and de novo design) that are necessary for a project. The computational design is followed by wet experimental tests (chemical synthesis, site-directed mutagenesis, protein expression, purification, in vitro activity assays, and in vivo tests etc.). These experiments are performed either in Dr. Zhan’s lab or in a close collaboration with internal and/or external experimental laboratories. Dr. Zhan’s unique “structure-and-mechanism-based drug design and discovery” efforts through integrated computational-experimental studies (supported by NIH, NSF, and other organizations) have been very productive, leading to exciting discovery of novel, promising therapeutics. Two of the therapeutic agents are in Phase II human clinical trials. The members of Dr. Zhan’s lab (including Graduate Students, Postdoctoral Fellows, Scientists, Visiting Scientists, and Visiting Professors) work in an interdisciplinary research environment. Some recent news about Dr. Zhan’s research: 12/28/2015: Long-acting cocaine-catalyzing enzymes (http://www.pnas.org/site/media/selections_12_28_15.xhtml#long); 11/20/2015: UK Awarded $6 Million to Further Develop Treatment for Cocaine Abuse (http://uknow.uky.edu/content/uk-awarded-6-million-further-develop-treatment-cocaine-abuse); 11/19/2015: You've Heard of Narcan, But What About an Overdose Drug for Cocaine? (http://wuky.org/post/youve-heard-narcan-what-about-overdose-drug-cocaine); 11/9/2015: New enzyme therapy shows proof of concept as treatment for cocaine overdose (http://www.sciencedaily.com/releases/2015/11/151109133907.htm); 3/12/2015: Viral Mechanism-Tat Modulates DAT -- Nature Chemical Biology Highlighting a Report (ACS Chem. Neurosci. 2015, 6, 658-665) from the MMBC (http://www.nature.com/nchembio/journal/v11/n4/full/nchembio.1779.html); 12/22/2014: Groundbreaking Computational Drug Design is College Publication Highlight of the Year (http://pharmacy.mc.uky.edu/display.php?id=1114); 3/18/2014: A Highly Efficient Cocaine-Detoxifying Enzyme Obtained by Computational Design (http://www.nature.com/ncomms/press_releases/ncomms0314.html). Dr. Zhan has published more than 300 papers in peer-reviewed journals. He currently services as an Editorial Board member of multiple journals (including Theoretical Chemistry Accounts, Clinical Pharmacology, Journal of Addiction Research & Therapy, Reports in Theoretical Chemistry, and Medicinal Chemistry: Current Research). He currently serves or has served as member of American Association of Pharmaceutical Scientists (AAPS) Fellow Selection Committee, member of National Biotechnology Conference (NBC) programming committee, and Chair of Computational Drug Design Focus Group (CDDFG) of AAPS. He has served as a reviewer of grant proposals for NIH, NSF, DOE, and many other national and international foundations, and won 2005 Emerging Computational Technology Prize, American Chemical Society (ACS) Division of Computers in Chemistry (received during the Fall 2005 ACS meeting, Washington DC, August 28 to September 1, 2005; ACS web page for the prize: http://oldwww.acscomp.org/Awards/emerging2005.html).


  • Development of reliable and efficient tools for drug design, discovery, and development
  • Integrated in silico, in vitro, and in vivo approaches to drug discovery and development
  • Protein engineering and development of therapeutic enzymes
  • Rational design, discovery, and development of novel therapeutic agents that may be small-molecules, peptides, or proteins
  • Translational research - from discovery to therapy

Recent Publications

  • Yuan Y., Quizon P.M., Sun W.L., Yao J., Zhu J., Zhan C.-G. (2016). Role of Histidine 547 of Human Dopamine Transporter in Molecular Interaction with HIV-1 Tat and Dopamine Uptake. Sci. Rep., 6, 27314. doi: 10.1038/srep27314..
  • Chen X., Xue L., Hou S., Jin Z., Zhang T., Zheng F., Zhan C.-G. (2016). Long-acting cocaine hydrolase for addiction therapy. Proc. Natl. Acad. Sci. USA, 113, 422-427.
  • Yao J., Yuan Y., Zheng F., Zhan C.-G. (2016). Unexpected reaction pathway for butyrylcholinesterase-catalyzed inactivation of "hunger hormone" ghrelin. Sci. Rep., 6, 22322. doi: 10.1038/srep22322.
  • Yuan Y., Huang X., Midde N. M., Quizon P. M., Sun W. L., Zhu J., Zhan C.-G. (2015). Molecular mechanism of HIV-1 Tat interacting with human dopamine transporter. ACS Chem. Neurosci., 6, 658-665. Research Highlight – “Viral Mechanisms: Tat modulates DAT”, Nature Chem. Biol. 2015, 11, 240.
  • Miller Z., Kim K. S., Lee D. M., Kasam V., Baek S. E., Lee K. H., Zhang Y. Y., Ao L., Carmony K., Lee N. R., Zhou S., Zhao Q., Jang Y., Jeong H. Y., Zhan C. -G., Lee W., Kim D. E., Kim K. B. (2015). Proteasome inhibitors with pyrazole scaffolds from structure-based virtual screening. J. Med. Chem., 58, 2016-2341.
  • Wei D., Tang M., Zhan C.-G. (2015). Fundamental reaction pathway and free energy profile for proteasome inhibition by syringolin A (SylA). Org. Biomol. Chem., 13, 6857-6865.
  • Chen X., Huang X., Geng L., Xue L., Hou S., Zheng X., Brimijoin S., Zheng F., Zhan C.-G. (2015). Kinetic Characterization of a Cocaine Hydrolase Engineered from Mouse Butyrylcholinesterase. Biochemical Journal, 466, 243-251.
  • Zheng F., Xue L., Hou S., Liu J., Zhan M., Yang W., Zhan C.-G. (2014). A highly efficient cocaine-detoxifying enzyme obtained by computational design. Nature Communications, 5, 3457.
  • Burikhanov R., Sviripa V. M., Hebbar N., Zhang W., Layton W. J., Hamza A., Zhan C.-G., Watt D. S., Liu C., Rangnekar V. M. (2014). Arylquin-1 targets vimentin to trigger Par-4 secretion for tumor cell apoptosis. Nature Chemical Biology, 10, 924-926.
  • Fang L., Chow K. M., Hou S., Xue L., Chen X., Rodgers D. W., Zheng F., Zhan C.-G. (2014). Rational design, preparation, and characterization of a therapeutic enzyme mutant with improved stability and function for cocaine detoxification. ACS Chemical Biology, 9(8), 1764-72.