Provost Lecture - Ken Dill: Pathways

Pathways: Routes Through Life, Science, and Protein Folding are Seldom Straight Lines

Eric Kaler credited Dill, who is the director of the Laufer Center for Physical and Quantitative Biology, with designing an elegant model for protein folding and biological evolution now acknowledged by scientists on a grand scale. He also established rules for protein folding that show promise with surgical glues for tissue engineering. Dill, a member of the National Academy of Sciences and co-author of the textbook Molecular Driving Forces, spoke about chemical pathways as analogous to water flowing along a river with all of the molecules beginning and ending in the same place. But the pathways, as in life, do not always follow a linear path, and are more often random, less directed, and less predictable. Dill gave the example of his boyhood in Oklahoma and how he envisioned his destiny, where boys from his time period either wanted to be a country and western singer or a baseball star modeled after native son Mickey Mantle. But like the pathways taken by molecules, "all of my friends from Oklahoma are not in this room (divergence) and all of the people in this room are not from Oklahoma (convergence)," he said. With so many options to choose from proteins and people have no idea where they are going to wind up.

Additionally, in protein folding, the pathways are more funnel-shaped than superhighway-shaped. The proteins are made up of 50 to 1,000 chains of amino acids in 3-D form adding up to 20-odd-thousand proteins in the human body.

The options available to proteins are analogous to the proverbial needle in the haystack. "Think of a golf course and they are looking to find one hole," Dill said.

"How could evolution create an eye?" Dill posed. "Why would organisms spend all of their energy making a half-eye that is no good?"

He showed a YouTube movie featuring himself and another scientist who raised the question, "intelligent design proponents say the eye is too complex but science says, 'Look at the evidence."

The scientists pointed to five stages of eye evolution from the most primitive mollusk to the most complex as found in an octopus, the result of millions of years of evolution.

"Evolution can take indirect routes," Dill said. By contrast, he cited the very rapid evolution of the HIV and MRSA viruses, as well as cancer cells that can become drug-resistant.

In summary, Dill said that the pathways of proteins folding have a huge number of options, are not always linear, can bifurcate along the way, and are not predictable from beginning to end or from the end back to the beginning.