at the 1992 "Frontiers of Science" symposium.

But this, said Alber, now at the University of California, Berkeley, is only the beginning of the benefits that could accrue. "We could design proteins that are useful to people but don't necessarily occur in nature." For example, pharmaceuticals that require no refrigeration could bring the benefits of modern medicine to the world's isolated and impoverished populations. Novel catalysts could be designed to mediate chemical reactions that are not found in biological systems, reactions that might be useful in the food or pharmaceutical industries.

THE IMPORTANCE OF THREE-DIMENSIONAL STRUCTURE

Although evolution has been building with proteins for 600 million years, scientists have only begun to understand the rudiments of how these substances work, and years or even decades may elapse before engineers will be able to systematically design proteins for specific tasks.

Three-dimensional structure determines function, Alber explained. Enzymes—the catalysts of living substances—fit their substrates as precisely as keys fit locks. For example, it is shape that allows the different enzymes that reside in the gastrointestinal tract to catalyze the disassembly of food molecules into the building blocks that the body uses for nourishment. But there are different enzymes to break down different types of protein and still others to dismantle starch into its constituent sugar molecules.

And it is shape that prevents the starch-digesting enzymes from allowing us to eat grass or bark. Cellulose, the woody material that prevents humans from grazing with the cattle, and from dining with termites on old, dead trees, is composed of chains of sugar molecules, just like starch. The difference between a two-by-four and potatoes or pasta is largely the result of slight differences in the way the sugar molecules are strung together. These slight differences render cellulose indigestible by starch-cleaving enzymes.

Like enzymes, cells of the immune system that adhere to invading microbes also fit their targets with the specificity of lock and key. Recognition is so precise that there are different antibodies for each disease.

"The problem [is] where does the structure come from?" says Alber. "Our work is aimed at understanding the architectural principles that



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