Laboratories
Home > Laboratories > Advanced Science Institute > Zhang Initiative Research Unit
Zhang Initiative Research Unit
Kam ZHANG
Initiative Research Scientist
Kam ZHANG (Ph.D.)
mail

Click

Research Areas

The complex biological functions of proteins are determined by their equally intricate three-dimensional structures. The correctly folded native structure is critical for the proper function of a protein in a cell. Small deviations from its native structure can often lead to malfunction of the protein and cause diseases. Our goal is to understand and modulate protein functions through computational studies of their structures. We are developing methods for protein structure prediction and applying design principles to create proteins with novel architectures, new biological functions or effective therapeutics. We are exploring new constraints to solve the X-ray crystallographic phase problem. We are also using the scaffold-based drug design method to discover new inhibitors for various drug targets.

Research Subject

  1. Direct methods of phase retrieval in protein crystallography
  2. Density modification and phase improvement in X-ray crystallography
  3. Computational protein structure prediction
  4. Protein folding and design
  5. Scaffold-based drug design

Related links

  1. RIKEN Advanced Science Institute Website_Laboratories PageNew Window
  2. Individual Website Laboratory PageNew Window

List of Selected Publications

  1. Zhang, K. Y. J.:
    "SQUASH - Combining Constraints for Macromolecular Phase Refinement and Extension."
    Acta Cryst., D49, 213-222(1993).
  2. Nieh, Y. P., and Zhang, K. Y. J.:
    "A two-dimensional histogram-matching method for protein phase refinement and extension."
    Acta Cryst., D55, 1893-1900(1999).
  3. O'Neil, J. W., Johnsen, K.., Kim, D. E., Baker, D., and Zhang, K. Y. J.:
    "Single site multations induce 3D domain-swapping in the B1 domain of Protein L from Peptostreptococcus magnus."
    Structure, 9. 1017-1027(2001).
  4. Zhang, K. Y. J.:
    "Multidimensional histograms for density modification."
    Methods in Enzymology, 374, 188-203(2003).
  5. Zhang, K. Y. J., Card, G. L., Suzuki, Y., Artis, D. R., Fong, D., Gillette, S., Hsieh, D., Neiman, J., West, B. L., Zhang, C., Milburn, M. V., Kim, S. H., Schlessinger, J., and Bollag, G.:
    "A Glutamine Switch Mechanism for Nucleotide Selectivity by Phosphodiesterases."
    Molecular Cell, 15, 279-286(2004).
  6. Card., G. L., Blasdel, L., England, B. P., Zhang, C., Suzuki, Y., Gillette, S., Fong, D., Ibrahim, P. N., Artis, D. R., Bollag, G., Milburn, M. V., Kim, S. H., Schlessinger, J., and Zhang, K. Y. J.:
    "A family of phosphodiesterase inhibitors discovered by cocrystallography and scaffold-based drug design."
    Nature Biotechnology, 23, 201-207(2005)
  7. Zhang, K. Y. J.:
    "Crystal structure of PDE families and the potential for rational drug design."
    Chapter 29 in Cyclic Nucleotide Phosphodiesterases in Health and Disease, pp 583-605, Eds. Joseph A. Beavo, Sharron H. Francis and Miles D. Houslay, CRC Press, Boca Raton/London/New York(2006).
  8. Zhang, K. Y. J., Milburn, M. V., and Artis, D. R.:
    "Scaffold-based drug discover."
    Chapter 6 in Structure-based Drug Discovery, pp 129-153, Eds. Harren Jhoti and Andrew Leach, Springer, Dordrecht/Boston/London(2007).
  9. Tsai, J., Lee, J. T., Wang, W., Zhang, J. Z., Cho, H., Mamo, S., Bremer, R., Gillette, S., Kong, J. Haass, N. K., Sproesser, K., Li, L., Smalley, K. S. M., Fong, D., Zhu, Y. L., Marimuthu, A., Nguyen, H., Lam, B., Liu, J., Cheung, I., Rice, J., Suzuki, Y.:
    "Discovery of a Novel Selective Inhibitor of Oncogenic B-Raf Kinase with Potent Anti-Melanoma Activity."
    PNAS, 105, 3041-3046(2008)
  10. Artis, D. R., Lin, J. J., Zhang, C., Wang, W. Mehra, U., Perreault, M., Erbe, d., Krupka, H. I., England, B. P., Arnold, J., Plotnikov, A. N., Marimuthu, A., Nguyen, H., Will, S., Signaevsky, M., Kral, J. Cantwell, J., Settachatgull, C., Yan, D. P., Hirth.:
    "Scaffold-based discovery of indeglitazar, a PPAR pan-active anti-diabetic agent."
    PNAS, 106, 262-267(2009)

Members

Principal Investigator

Kam ZHANG
Initiative Research Scientist

Postdoctoral Fellow

Kamlesh Kumar SAHU
Postdoctoral Researcher
Ashutosh KUMAR
Postdoctoral Researcher
Taeho JO
Postdoctoral Researcher
David SIMONCINI
Postdoctoral Researcher
Muhammad MUDDASSAR
Postdoctoral Researcher
Arnout Richard Dominiek VOET
Postdoctoral Researcher

Student Trainee

Rojan SHRESTHA
International Program Associate

Technical Assistant

Francois Charles Matthieu BERENGER
Technical Staff I