Cancer drug design: Long range communications in cytoskeleton proteins

CHED 950

Farhana Momin,, Department of Chemistry, Mount Holyoke College, 2631 Blanchard Campus Center, 50 Collge Street, South Hadley, MA 01075 and Ruxandra I. Dima,, Department of Chemistry, University of Cincinnati, Cincinnati, OH 45221.
An important class of cancer drugs targets microtubules. We postulate that, to be effective, these drugs must bind to regions involved in long range communications (allostery) in microtubules. This is because binding in such regions will allow drugs to influence the dynamic instability of microtubules which is a hallmark of their function. To probe the network of positions involved in allostery in tubulin, we analyzed the evolutionary data on tubulin employing a combination of bioinformatics methods. I will present the results of our analysis that led to the identification of clusters of allosteric residues on both tubulin monomers. Using additional criteria such as the coordination number, the solvent accessibility, and the location of the residues in a structure, we propose potential drug binding sites. As illustration, I will present our results for the cancer drug Taxol which correlate well with the experimental data.