David Beratan and the Inner Workings of the Machines of Biology

Chemist illuminates the form and function of proteins

Chemist David Beratan

Duke Chemist David Beratan combines innovative research with innovative education. For his contributions to the field of chemistry and for his mentoring of disadvantaged high school students, Beratan will receive the Herty Medal from the Georgia Section of the American Chemical Society (ACS) on Sept. 17.

The Herty Medal, given annually since 1933, recognizes outstanding work and service by a chemist in the southeast. Beratan uses theoretical methods to study the relationship between structure and function in biological and synthetic molecules.

Beratan’s research focuses on proteins, which he calls the “machines of biology.” Proteins are large molecules that fold into intricate three-dimensional shapes. His work describes the way a protein’s shape and its “wiggling and jiggling” affect how—and how fast—electrons move inside the protein.

“With that knowledge we can predict these critical electron transfer rates,” he said. “And why do we care? The answer is bioenergetic reactions.”

Bioenergetic reactions, such as photosynthesis and metabolism, occur in every living organism. The energy transfer involved in these reactions occurs through the movement of electrons. Understanding electron transfer rates helps explains how different molecules perform different functions.

“Bioenergetic reactions are critically important in biology and biomedicine,” Beratan said. “And from the standpoint of a physical chemist, they are fascinating reactions because electrons are fundamentally quantum mechanical objects. They are so tiny and light, they have wave-like characteristics. This is a situation where biology and quantum mechanics really meet head on.”

Because electrons act like waves, their movement can create interference. The interference can be constructive when two wave crests merge to create a larger one, or destructive when a wave and a trough cancel each other out.

“Once you understand these phenomena you want to manipulate them,” Beratan said. For example, he and his group have suggested a way that light might be used to turn off destructive interference. An experimental group at Tulane University in New Orleans is testing the idea. A possible application: light-powered computers that could be a thousand times smaller than today’s electricity-powered computers.

The applications of Beratan’s work don’t stop there. Work coming out of his lab is informing research into creating fuel from solar energy via artificial photosynthesis. It’s illuminating how our bodies repair DNA damage because of exposure to sunlight, an understanding that may one day translate into a biomedical application. And it’s also leading to improved methods of designing new drugs.

Indeed, he collaborates with various colleagues at Duke and beyond to increase the efficiency of pharmaceutical exploration. If someone has a function in mind for a hypothetical drug, Beratan and his students can use their knowledge of proteins and of molecular design principles to help identify molecules likely to have such a function.

“We’re helping them guide their chemical synthesis so as to maximize the chance that they’ll make molecules of potential value as a drug,” he said.

Beratan is the R. J. Reynolds Professor of Chemistry and, reflecting his interdisciplinary approach to research and teaching, he holds secondary appointments in biochemistry and physics. “Duke’s absence of silos and boundaries suits me well in my research,” he said. “I talk to physicists and biochemists and mathematicians and computer scientists.”

Ever since he joined the faculty at Duke in 2001, he’s participated in ACS’s Project SEED, helping to place disadvantaged high school students in labs for a summer of research experience—and he’s mentored about a dozen of these students himself over the years. The vast majority of the students have gone on to attend college. “It’s been quite a rewarding program,” he said.

He’s also designed interdisciplinary courses for Duke undergraduates and a distance learning course for graduate students studying at different universities. Currently, he’s working on a Duke Signature Course, one of a collection of courses intended to encourage undergraduates to engage with “big questions” through interdisciplinary exploration.

His course, called “How does biology work?” will introduce students to Beratan’s research sweet spot—the intersection of chemistry, physics, and biology.