Dispatches from the bio frontier

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By Roger Snodgrass

The time is ripe for the general public to become conversant with the basic ingredients of modern biology and particularly about structural genomics, one of its promising branches.

By now intellectually curious adults and precocious children will surely have noticed at least one of those colorful swirling ribbons that are used to represent a protein.

But what are proteins beyond the diet, and what is their relation to the squigglies?

“Proteins are little molecular machines,” said Thomas Terwilliger, a biochemist at Los Alamos National Laboratory and one of the world’s leaders in developing methods for developing three-dimension pictures of proteins. “They do all kinds of things, and that’s why we like to harness them to do things we would like them to do.”

Because knowledge of the structures themselves is useful, biologists have gone to some lengths to make, purify and grow crystals of proteins that can be x-rayed and interpreted in terms of the chains of amino acids from which they are constituted.

That’s how they get to be color-coded curlicues, which are a kind of shorthand in the language of molecular graphics that offers a different way to look at the protein.

“The ribbon diagram shows where the atoms are,” Terwilliger said. “The protein is really a solid object that doesn’t have big holes. What’s important in the shape isn’t so much the ribbons themselves, it’s the shape of the surface.”

Apart from the overall pursuit of all the components of life and how they work together, there are practical outcomes for this research.

“Knowing the shapes of proteins, allows pharmaceutical companies to make chemical compounds that fit into the crevices, or let’s say ‘the business end’ where they do their work and interfere with the proteins’ actions.” Terwilliger said. “This is the way many common antibiotics and other drugs work. They interfere with the proteins’ work.”

One of the most familiar examples, he said, is the way aspirin interferes with proteins that cause inflammation, relieving symptoms from arthritis and other common bodily pains.

Beginning Friday, Terwilliger will discuss his work and what is happening in the field of structural genomics in the latest lecture tour of the Frontiers in Science lecture series, sponsored by the Fellows of the Laboratory.

He discusses these processes in the context of a cooperative international research effort that aims to inventory the shapes of proteins from tuberculosis, so that pharmaceutical responses can be developed.

The Frontiers in Science series is presented one night each in several communities in the region.

Terwilliger’s series will begin Friday in the Duane Smith Auditorium at Los Alamos High School. It starts at 7 p.m., as do all the talks in the series.

On Nov. 17, the venue will be the Taos Convention Center in Taos.

The next day, Nov. 18, Terwilliger will speak at the James A. Little Theater, at the New Mexico School for the Deaf, 1060 Cerillos Rd. in Santa Fe.

Finally, on Nov. 19, the series will conclude at the New Mexico Museum of Natural History and Science 1801 Mountain Rd., N.W. in Albuquerque.

Terwilliger is a Laboratory Fellow with many honors. Among them, he won a Presidential Young Investigator Award, 1985-1990 and was named a Fellow of the American Association for the Advancement of Science in 2000.