New Nature Chemical Biology paper on Aurora A kinase, a potential melanoma target

In collaboration with the Nicholas Levinson lab at the University of Minnesota, we have just published a paper in Nature Chemical Biology using experiment and simulation to probe the mechanism of allosteric activation of Aurora A kinase (AurA). AurA is found to be hyperphosphorylated in approximately 10% of melanoma patients due to mutations that deactivate the protein phosphatase PP6, leading to defects in chromosome segregation and genomic stability. 

AurA kinase plays two distinct roles in mitosis, with a centrosomal pool of kinase activated by phosphorylation similarly to other kinases, but a separate pool controlled by a more exotic mechanism of binding to the spindle-associated protein Tpx2. Using an aggregate of several microseconds of data generated on Folding@home to study wild-type AurA and some engineered mutants, we helped the Levinson lab puzzle out a key role of highly stable waters localized in the active site that mediate allosteric communication in the Tpx2-mediated activation of AurA.

Soreen Cyphers, Emily F Ruff, Julie M Behr, John D Chodera, and Nicholas M Levinson.
A water-mediated allosteric network governs activation of Aurora kinase A
Nature Chemical Biology, in press. [DOI] [GitHub]

We have made all the explicit-solvent Folding@home simulation data and analysis scripts used in this paper available for download:
http://github.com/choderalab/AurA-materials

The trajectory data itself is too large to share via GitHub, so we make it available via the Open Science Framework.

Help us reach one million folders on Folding@home!

Our lab is a core member of the Folding@home Consortium, a research network of 11 laboratories around the world that use Folding@home to study the molecular mechanisms underlying cancer and other diseases and identify new routes toward therapies. Together, we are aiming to recruit one million volunteers donating compute cycles to help us! 

Please join us, especially if you have a GPU: Folding@home can harness the power of your GPU
It costs nothing (other than your electrical bill) and provides a way to donate your idle computer cycles to biomedical research.

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