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New Argonne study may shed light on protein-drug interactions
Date:1/15/2008

ARGONNE, Ill. (January 15, 2008) -- Proteins, the biological molecules involved in virtually every action of every organism, may themselves move in surprising ways, according to a recent study from the U.S. Department of Energys Argonne National Laboratory that may shed new light on how proteins interact with drugs and other small molecules.

While scientists had expected proteins to behave similarly in regions of high and low protein concentration from as high as 30 percent protein to less than one percent protein, respectively they instead found that proteins had a much larger range of motion and could contort themselves into many more configurations in the dilute solutions. The difference is comparable to skipping through an open field or being crammed into a crowded elevator, said Argonne biochemist Lee Makowski, who headed the project.

This study represents a novel approach to characterizing the ways in which proteins move around in solution to interact with other molecules, including drugs, metabolites, or pieces of DNA, and relied on the intense x-ray beams available at Argonnes Advanced Photon source.

The study of proteins had long focused almost exclusively on their structures, parts of which can resemble chains, sheets or helices. To determine these, scientists use high-energy X-rays to take snapshots of proteins frozen in a single conformation within a highly ordered crystal. However, biologists had made relatively little progress in using these pictures to show how proteins can reconfigure themselves in different environments.

Proteins are not static, theyre dynamic, Makowski said. Part of the common conception of proteins as rigid bodies comes from the fact that we know huge amounts about protein structures but much less about how they move.

For over a century, the standard model of protein behavior depicted them as inflexible locks that could interact only with a small set of equally rigid mol
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Contact: Steve McGregor
smcgregor@anl.gov
630-252-5580
DOE/Argonne National Laboratory
Source:Eurekalert

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