Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

New study may shed light on protein-drug interactions

17.01.2008
Proteins, the biological molecules that are 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 Energy's Argonne National Laboratory that may shed new light on how proteins interact with drugs and other small molecules.

This study, which relied on the intense X-ray beams available at Argonne's Advanced Photon Source, uses a new approach to characterize the ways in which proteins move around in solution to interact with other molecules, including drugs, metabolites or pieces of DNA.

"Proteins are not static, they're dynamic," said Argonne biochemist Lee Makowski, who headed the project. "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."

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.

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 1 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," Makowski said.

For more than a century, the standard model of protein behavior depicted them as inflexible "locks" that could interact only with a small set of equally rigid molecular "keys." Even today's introductory biology courses rely on descriptions of protein behavior that require them to swivel and pivot very little as they interact with other biological molecules, according to Makowski. "That's a very powerful image but it's not the whole story," he said. "We've learned that proteins in solution can take on an entire ensemble of slightly different structures and that, for most proteins, this ensemble grows much larger as you go to lower and lower concentrations."

Makowski and his colleagues were also surprised to discover that environmental conditions strongly influence which state in this "ensemble" of conformations a protein prefers to enter. Most of a protein's common configurations have a functional purpose, he said, as it is "not likely to twist itself into something completely irrelevant to its function."

For example, one of the five proteins examined in the study, hemoglobin, has two favored conformations: one in which it binds oxygen very readily and one in which it does not. When hemoglobin is placed in a solution that contains a great deal of available oxygen, it spends most of the time in the former state, but when oxygen is not easily accessible, it usually flips into the latter. "We now know that in dilute solutions, hemoglobin can actually take on both conformations — even in the absence of oxygen," he added.

By keeping all of the environmental factors the same save for the protein concentration in the solution, Makowski and his team discovered another surprising result. Scientists had known for many years that when proteins are too concentrated, they aggregate and fall out of solution. However, biochemists previously had difficulty explaining why a similar effect also occurs in overly dilute solutions.

Proteins have hydrophobic – or "water-hating" – core regions that try to avoid touching water if at all possible. Because of this characteristic, proteins will rearrange themselves to protect these regions from coming into contact with water. In dilute solutions, however, Makowski's team discovered that proteins fluctuate far more than in concentrated solutions, and these fluctuations expose the proteins' hydrophobic core, making them more likely to stick to one another or to the container walls.

The results of the research appear in the January 11 issue of the Journal of Molecular Biology.

Argonne National Laboratory, a renowned R&D center, brings the world's brightest scientists and engineers together to find exciting and creative new solutions to pressing national problems in science and technology. The nation's first national laboratory, Argonne conducts leading-edge basic and applied scientific research in virtually every scientific discipline. Argonne researchers work closely with researchers from hundreds of companies, universities, and federal, state and municipal agencies to help them solve their specific problems, advance America 's scientific leadership and prepare the nation for a better future. With employees from more than 60 nations, Argonne is managed by UChicago Argonne, LLC for the U.S. Department of Energy's Office of Science.

Steve McGregor | EurekAlert!
Further information:
http://www.anl.gov

More articles from Studies and Analyses:

nachricht Climate change and air pollution damaging health and causing millions of premature deaths
30.11.2018 | International Institute for Applied Systems Analysis (IIASA)

nachricht Reading rats’ minds
29.11.2018 | Institute of Science and Technology Austria

All articles from Studies and Analyses >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Researchers develop method to transfer entire 2D circuits to any smooth surface

What if a sensor sensing a thing could be part of the thing itself? Rice University engineers believe they have a two-dimensional solution to do just that.

Rice engineers led by materials scientists Pulickel Ajayan and Jun Lou have developed a method to make atom-flat sensors that seamlessly integrate with devices...

Im Focus: Three components on one chip

Scientists at the University of Stuttgart and the Karlsruhe Institute of Technology (KIT) succeed in important further development on the way to quantum Computers.

Quantum computers one day should be able to solve certain computing problems much faster than a classical computer. One of the most promising approaches is...

Im Focus: Substitute for rare earth metal oxides

New Project SNAPSTER: Novel luminescent materials by encapsulating phosphorescent metal clusters with organic liquid crystals

Nowadays energy conversion in lighting and optoelectronic devices requires the use of rare earth oxides.

Im Focus: A bit of a stretch... material that thickens as it's pulled

Scientists have discovered the first synthetic material that becomes thicker - at the molecular level - as it is stretched.

Researchers led by Dr Devesh Mistry from the University of Leeds discovered a new non-porous material that has unique and inherent "auxetic" stretching...

Im Focus: The force of the vacuum

Scientists from the Theory Department of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science (CFEL) in Hamburg have shown through theoretical calculations and computer simulations that the force between electrons and lattice distortions in an atomically thin two-dimensional superconductor can be controlled with virtual photons. This could aid the development of new superconductors for energy-saving devices and many other technical applications.

The vacuum is not empty. It may sound like magic to laypeople but it has occupied physicists since the birth of quantum mechanics.

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

New Plastics Economy Investor Forum - Meeting Point for Innovations

10.12.2018 | Event News

EGU 2019 meeting: Media registration now open

06.12.2018 | Event News

Expert Panel on the Future of HPC in Engineering

03.12.2018 | Event News

 
Latest News

Small but ver­sat­ile; key play­ers in the mar­ine ni­tro­gen cycle can util­ize cy­anate and urea

10.12.2018 | Life Sciences

New method gives microscope a boost in resolution

10.12.2018 | Physics and Astronomy

Carnegie Mellon researchers probe hydrogen bonds using new technique

10.12.2018 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>