If not for family history and a fortune cookie, Dr. Carol Hall might be finding ways to process hydrogen energy instead of looking for clues that might cure diseases. Hall, the Camille Dreyfus Distinguished University Professor of Chemical and Biomolecular Engineering, uses advanced computer simulations to study the motion of various proteins, hoping to unlock the secret to the onset of neurodegenerative diseases like Alzheimer’s, Parkinson’s, and Lou Gehrig’s.

Two dozen such diseases are characterized by a similar protein structure called an amyloid. One of them, Pick’s disease, killed Hall’s father almost two decades ago, and her mother is now showing the early symptoms of an amyloid disease. “This is very personal to me,” Hall says. “I need to help medical researchers find a treatment for these diseases.” Still, it wasn’t until she cracked open a fortune cookie a few years after her father’s death and read the message, “You could prosper in medical research,” that she decided to focus her efforts on protein dynamics.



Proteins normally fold in on themselves, but under some conditions, they stretch out and mass together. The molecules intertwine and stack next to each other like sheets of paper, creating fibrils that later appear as plaques on the brain. Using computer simulations, Hall has shown how temperature and the concentration of protein molecules influence the rate at which fibrils form. “It’s not all or nothing, with some proteins massing together while others don’t,” she says. “It depends on conditions.”

The protein strands move slowly, and even the most powerful supercomputers have trouble following their movements on an atomic level because of the number of calculations involved. So Hall has developed algorithms that study molecules at an “intermediate resolution,” meaning that her computer program pulls back slightly for a wider-angle look at the proteins over a longer period of time—milliseconds instead of nanoseconds. “It’s like looking through a shower curtain,” she says. “It’s a little fuzzy, but we get a general idea of what’s happening.”



With funding from the National Institutes of Health, Hall has examined polyalanine, a protein associated with a hereditary disease that primarily afflicts Welsh people, because it’s fairly easy to model. She also has started working on a simplified model of a peptide linked to Alzheimer’s disease and says she often runs simulations based on suggestions and hypotheses made by medical researchers. “I feel like I’m part of a community trying to figure this out.”


For more information, please visit
http://turbo.che.ncsu.edu/