July 8, 2005
Jack Tuszynski Dept of Physics,University of Alberta
(audio of the talk)
Rational Drug Design for Cancer Using Molecular Dynamics Simulations

Alpha-beta tubulin and microtubules are currently one of the most successful targets for anti-cancer drugs available. However, despite the overall success of the vinca alkaloid and taxoid drug families serious side effects such as neurodegradation seriously impair the prognosis of the patient. It should be taken into consideration when designing new cancer medication that humans produce many beta tubulin isotypes which are then preferentially expressed in different tissues. In particular, beta-III is over expressed in cancer cells, such as prostate and breast cancer, and is also taxoid resistant. Thus, designing a beta-III specific anit-cancer drug should in principle increase efficacy while decreasing side-effects. In our research we explore the conformational and functional changes in tubulin due to GTP-hydrolysis and isotype specific mutations using homology modelling and molecular dynamics energy minimization schemes for tubulin isotypes. Elucidating the molecular effects of structural changes and dynamic transformations of the protein
will lead to the development of a beta-III specific agent. I will report on the progress made in this work so far.

Acknowledgements:
This project has been funded by NSERC, MITACS, PIMS, US Department of Defense, Oncovista LLC (San Antonio, TX) and Technology Innovations LLC
(Rochester, N.Y)

Biography:
Jack Tuszynski is a Professor in the Department of Physics at the University of Alberta and previously held a faculty position in the Physics Department at Memorial University in Newfoundland. He has held visiting professorships at H. Heine Universitat Dusseldorf, Germany and at the Technical University of Denmark. He was also the recipient of a prestigious Alexander von Humboldt fellowship and of a McCalla Professorship.