Electrostatic Contributions to Colchicine Binding within Tubulin Isotypes

Abstract

Tubulin, the structural subunit of microtubules, is the target of some highly successful anti-tumor drugs. Most of these drugs bind to the β-tubulin resulting in the inhibition of microtubule dynamics and eventually cell death. The varied cellular distribution of several human isotypes of β -tubulin provides a platform upon which to construct novel chemotherapeutic agents that are able to differentiate between these types of cells. To test this hypothesis, we have previously created homology models of the nine most frequently observed human β -tubulin isotypes and analyzed them for differences in the colchicine-binding site. Here, we describe the electrostatic properties of the colchicine binding site and how this may affect calculated drug binding affinities between the β -tubulin isotypes.

Keywords:

• Microtubule
• Tubulin
• Colchicine
• Electrostatics
• APBS

Acknowledgments

This research was directly funded through grants from NSERC, MITACS, the Alberta Cancer Foundation and the additional financial support from the Allard Foundation.

Declaration of Interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.