Notre Dame’s Jeffrey Peng is a filmmaker of sorts, but you won’t see his work at your local multiplex theater any time soon. The biggest fans of the assistant professor of biochemistry’s work are pharmaceutical chemists who design drugs.
Using a powerful nuclear magnetic resonance spectrometer, Peng records the motion of molecules. “Essentially we can give you a ‘movie’ of how molecules shift and move on an atomic scale,” he says. Such information is especially valuable for drug design because the molecules involved in disease are inherently dynamic. “Essentially they’re incredibly small machines with moving parts,” Peng says.
HIV protease, an enzyme critical to AIDS infection, is a prime example. “It’s kind of like PacMan,” the ND biochemist explains. “The enzyme’s molecular structure moves like jaws that open up and bind with the ‘victim’ molecule.
“If you want to design an effective inhibitor drug to prevent infection, you need to understand that movement to block those jaws. And that’s where we come in,” Peng says.
Among other drug resistance projects, the Notre Dame researcher currently is working on the HIV protease problem with Dr. Celia Schiffer and colleagues at the University of Massachusetts. The Schiffer group found that many HIV protease inhibitor drugs are self-defeating because they are larger in molecular size than the binding site. Consequently they introduce interactions which set up new grounds for mutations, Peng explains.
With a better understanding of the dynamics of the system, the hope is that this might be prevented, which is where Peng and his spectrometer “movies” come in.
John Monczunski is an associate editor of Notre Dame Magazine.