Guest post from Dr. John Chodera, UC Berkeley
Kinases [http://en.wikipedia.org/wiki/Kinase] are the molecular logic gates of the cell. These important proteins integrate critical signaling information in every cell of our bodies, becoming active only when specific upstream signals are received. However, in many kinds of cancer, mutations can emerge in one or more kinases that cause them to ignore these regulatory signals and become active all the time. If these kinases are involved in cell division, this can erroneously cause cells to keep dividing even when they shouldn't, potentially resulting in a form of cancer.
Our group [http://choderalab.org] is using Folding@Home to understand how some successful anti-cancer therapeutics (like imatinib [http://en.wikipedia.org/wiki/Imatinib]) are able to selectively target the targeted disease-causing kinases while minimally interfering with other normally-functioning kinases. A deeper understanding of this selectivity would help recapitulate the success seen in treating some cancers by aiding the design of novel therapeutics targeting other cancers. Up to now, the origin of this selectivity has been elusive because it appears that highly selective drugs like imatinib can bind in essentially the same way to the highly similar Abl and Src kinases, despite the fact that it binds Abl well and Src poorly (see Figure). It is now believed these differences in binding are due to conformational preferences of the kinase for different geometries, something that had been traditionally hard to study but is well-suited to techniques we originally developed to study protein folding problems on Folding@Home.
Stay tuned for future updates on how Folding@Home is helping our study of kinase inhibitors and cancer!