Testing Protein Recipes

Tidor is using the CRAY C90 at Pittsburgh to carefully explore how changes in the zipper's structure affect its stability. These computational studies offer a powerful new way to extend the benefits of laboratory experiments comparing normal and mutated proteins. In the mutations, one or more amino acids, the building blocks of proteins, are changed. By making enough mutants and studying them in the lab, it's possible to understand how every amino acid, each of which has many interactions with others in the protein's structure, affects the protein's function.

But it's a daunting experimental task, somewhat like testing the role of each ingredient in a recipe by making the dish over and over again, varying the ratio of ingredients each time. With computer simulations, explains Tidor, you can study the role of each ingredient without re-making the dish. In essence, the computer modeling allows researchers to investigate hundreds of different mutations without actually making them. Key features identified in the modeling can then be tested in the lab.

"This provides a short-cut," says Tidor, "to one of our major goals -- a fundamental understanding of interactions responsible for the structure and action of biological molecules in general, and the leucine zipper in particular. Our long-term aim is to use new insights into the fundamental rules of protein structure to design entire new molecules with custom properties."

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