This artist's rendering shows a ribbon diagram of the protein T4 phage lysozyme. Image courtesy of Ohio State.

By Ashley Yeager

If you ask vacationers about packing, they’ll probably tell you about over-stuffed suitcases and inflatable beach toys. But if you ask Yale physicist Corey O’Hern, he’ll tell you packing is about pockets, proteins and geometry.

“You may not believe it or may not have heard about it, but I’m going to argue that just geometry is important for understanding protein structure,” and “that makes protein structure look like a packing problem,” O’Hern said at a Sept. 26 physics colloquium. The protein packing problem and solving it could have implications for drug design.

O’Hern first learned about packing problems in physics as an undergraduate at Duke in the early 1990s. Working with Duke physicist Bob Behringer, he tried to explain how corn and coffee beans get jammed in their dispensers. O’Hern continued this type of work as a graduate student at the University of Pennsylvania and then earned a faculty post as a theorist in Yale’s engineering and applied science department.

“I didn’t believe in fate until I went to Yale and learned about Fred Richards. Now I do,” O’Hern said, explaining that the Yale biophysicist was interested in the structure of proteins and the “interior packing,” or arrangement, of their amino acids. O’Hern said Richards thought of proteins as a jigsaw puzzle and tried to figure out how the weird pieces fit together.

To better understand a protein’s geometry, Richards would trace water molecules over the surface of its amino acids. He thought that the inner folds of proteins were “well-packed” because the strong attractions of the atoms in those areas. “I don’t completely believe Richards’ results,” but the work “made me feel destined to get in on the research,” O’Hern said.

He now looks at how tightly animo acid molecules fit together in certain regions of the protein, T4 phage lysozyme. To study its packing properties, O’Hern simulates the energy and entropy in the pockets, or cavities, of the lysozyme’s inner folds. His early results suggest that the most stable forms of the protein have the most entropy, or randomness, among the amino acids in the pockets.

That way of packing is definitely counter-intuitive, O’Hern said. He’s still working on how the results are possible and, in a broader sense, how they could affect packing and folding of drugs to improve their effectiveness.