Sussman/Silman Group Movies

The use of computer graphics greatly aids the visualization and understanding of the 3D structures of macromolecular structures and their conformational changes. This approach was pioneered by Cyrus Levinthal (Levinthal (1966). To get a feeling for the value of this we have prepared a series of short movies showing key aspects of a number of the molecules we are studying and changes in their struture related to their funciton.

Acetylcholinesterase (AChE)

Acetylcholinesterase (AChE)  
  • Nature's Vacuum Cleaner - Binding of ACh to AChE (Movie by R. Gillilan, I. Silman & J.L. Sussman)
  • References:

    • Sussman, J. L., Harel, M., Frolow, F., Oefner, C., Goldman, A., Toker, L. & Silman, I.
      Atomic structure of acetylcholinesterase from Torpedo californica: a prototypic acety lcholine-binding protein.
      Science 253, 872-879 (1991). [Abstract] ] [PDF]

    • Sussman, J. L. & Silman, I.
      Acetylcholinesterase: structure and use as a model for specific cation-protein interactions.
      Curr Opin Struct Biol 2, 721-729 (1992). [Abstract]

    How synchrotron radiation can rapidly cause specific damage to a protein

    Drug Discoveries  
  • Radiation damage (Movie by R. Gillilan, I. Silman & J.L. Sussman)
  • Site-specific radiation damage caused to AChE by synchrotorn raditiaon (Movie by G. Kryger)

    References:

    • Weik, M., Ravelli, R. B. G., Kryger, G., McSweeney, S., Raves, M., Harel, M., Gros , P., Silman, I., Kroon, J. & Sussman, J. L.
      Specific chemical and structural damage to proteins produced by synchrotron radiation.
      Proc Natl Acad Sci USA 97, 623-628 (2000). [Abstract] [PDF] [Cover]

    • Weik, M., Ravelli, R., Silman, I., Sussman, J. L., Gros, P. & Kroon, J.
      Specific protein dynamics near the solvent glass transition assayed by radiation-induced str uctural changes.
      Protein Sci 10, 1953-1961 (2001). [Abstract] [PDF]

    • Weik, M., Kryger, G., Schreurs, A. M., Bouma, B., Silman, I., Sussman, J. L., Gros, P. & Kroon, J.
      Solvent behaviour in flash-cooled protein crystals at cryogenic temperatures.
      Acta Crystallogr D Biol Crystallogr 57, 566-573 (2001). [Abstract]

      [PDF]

    • Weik, M., Berges, J., Raves, M. L., Gros, P., McSweeney, S., Silman, I., Sussman, J. L., Houeee-Levin, C. & Ravelli, R. B. G.
      Evidence for the formation of disulfide radicals in protein crystals upon X-ray irradiation.
      J Synchrotron Rad 9, 342-346 (2002). [Abstract] [PDF]

    • Colletier, J.P., Fournier, D., Greenblatt, H.M., Stojan, J., Sussman, J.L., Zaccai, G., Silman, I. &, Weik, M.
      Structural insights into substrate traffic and inhibition in acetylcholinesterase
      EMBO J 25, 2746-2756 (2006). [Abstract] [PDF]

  • Conformational changes upon ligand binding

    Drug Discoveries  
  • Reaction products of AChE & VX reveal a mobile HIS (Movie by R. Gillilan, I. Silman, C. Millard & J.L. Sussman)

    References:

    • Millard, C. B., Koellner, G., Ordentlich, A., Shafferman, A., Silman, I. & Sussman, J. L.
      Reaction products of acetylcholinesterase and VX reveal a mobile histidine in the catalytic triad.
      J Am Chem Soc 121, 9883-9884 (1999). [PDF]

    • Bar-On, P., Millard, C. B., Harel, M., Dvir, H., Enz, A., Sussman, J. L. & Silman, I.
      Kinetic and structural studies on the interaction of cholinesterases with the anti-Alzheimer drug rivastigmine.
      Biochemistry 41, 3555-3564 (2002). [Abstract] [PDF]
  • Visualizing conformational changes in AChE via morphing (Movies by T. Zeev-Ben-Mordehai, I. Silman & J.L. Sussman)

    Cholinesterase Like Adhesion Molecules (CLAMs)  
  • Morphing of native TcAChE to MIP/TcAChE structure. (Details Fig 3 in ref below)
  • Morphing of native TcAChE to methylphosphonyl/TcAChE structure. (Details Fig 4 in ref below)
  • Morphing of native TcAChE to TcAChE/FAS-II complex (Details Fig 6 in ref below)
  • Morphing of TcAChE/FAS-II complex to hAChE/FAS-II complex (Details Fig 7 in ref below)
  • Morphing of native TcAChE structure to native DmAChE structure(Details Fig 8 in ref below)

    (To download any of the above movies, right click on the link, and "Save as...")

    References:

    • Zeev-Ben-Mordehai, T., Silman, I. & Sussman, J.L.
      Acetylcholinesterase in motion: Visualizing conformational changes in crystal structures by a morphing procedure.
      Biopolymers 68, 395-406 (2003). [Abstract] [PDF]