A new article by Visiting Assistant Professor in Computer Science Kelly Thayer and students in her Spring 2017 Scientific Computing class is challenging conventional metrics used in allosteric signaling—the regulation of an enzyme by a binding molecule at a site other than the enzyme’s active site.
“What’s special about allostery is that a molecule called an allosteric effector binds at one location, and the change happens somewhere else,” Thayer explained. “What we were trying to understand was: How does that signal get across?”
Their research, published in the Dec. 12, 2017 issue of PLOS ONE, has implications when applied to practical areas of pharmaceutical development. According to Thayer, “It opens up a lot of possibilities for exploring other areas for allosteric regulation on the protein surface. One of the things we think about and study in this lab is how to design drugs to modulate protein activity so we can help people who are sick. If you use the pathway model, you’ll look right on the path, and that’s it. But if the pathway model is wrong, you might engineer the drug incorrectly or altogether miss design opportunities for developing new medicines.”
While publication was cause for celebration and a triumph of interdisciplinary collaboration (the authors are affiliated with the mathematics, astronomy and chemistry departments), Thayer also notes that it was somewhat bittersweet in that one of the co-authors, Jesse Galganov ’17, was not around to share in it. (Galganov has been missing since September 2017 and was last seen backpacking in Peru.)
“Really, the success of this project was the coalescence of people from different fields sharing their insight and contributions. If any one of us had been absent from the project, it would have never gone forward. So it was hard for Avi [Stein] and me not to be able to celebrate being published with Jesse.”