NIH awards Argonne $800,000 to develop tool to measure
distances within proteins
Precise molecular ruler could play role in development
of new drugs
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ARGONNE, Ill. (Sept. 3, 2008) — Scientists at the U.S. Department of Energy's
(DOE) Argonne National Laboratory have won an $800,000 EUREKA award from
the National
Institutes of Health (NIH) to develop MADMAX, a precise molecular ruler
for measuring distances within a protein.
MADMAX, which stands for the Multi-wavelength Anomalous Diffraction using
Medium Angle X-ray solution scattering, would not only dramatically reduce
the time necessary to reveal the behaviors of a protein, but could provide
a new tool for pharmaceutical companies developing new drugs such as protease
inhibitors for the treatment of HIV. It could also be a stark improvement to
the decades-old method of crystallizing proteins, which could involve the use
of harsh chemicals and can show how a protein is structured but often provides
precious few clues as to how it moves in nature.
"There's almost nothing that a protein does that doesn't involve some movement," said
Lee Makowski, principal investigator of the project. "Proteins have to move,
and understanding that movement is key to figuring out how the proteins work."
MADMAX will precisely measure the inter-atomic distances between different
parts of proteins in a solution by using selenium to 'tag' the proteins so
the labels can be detected via the X-ray scattering. The selenium is easily
incorporated into proteins, allowing for their study while not interfering
with their function.
The proteins in solution are then hit with a beam of X-rays, and the scattering
is used to determine the distances between selenium atoms in the protein. When
the protein moves, the distances change and the movements of the protein can
be measured with great accuracy.
"If successful, MADMAX would change how we study proteins and protein motion," Makowski
said. "That's a huge thing."
MADMAX would allow scientists to see how a protein changes as a result of
its environment, observe how ligands bind to a proteins' surface and follow
the process of protein or RNA folding. It would also give pharmaceutical companies
the chance to observe how their drugs interact with proteins, potentially saving
time and expenses by providing them with unique insight into the mechanism
of the drugs' action.
The MADMAX program will take advantage of the Argonne's Advanced
Photon Source,
the brightest source of X-rays in the Western Hemisphere, and open to 3,500
users per year.
The MADMAX program is set to run for four years and will determine if the
method would be suitable for the study of proteins on a routine basis. The
team will begin by developing software and data collection protocols and then
move on to study well known compounds such as hemoglobin and HIV protease to
check the accuracy of the method.
The EUREKA program – designed to encourage 'Exceptional Unconventional Research
Enabling Knowledge Acceleration' – is in its first year and is funded by the
NIH to support exceptionally innovative research which has potential to have
a high impact in the scientific community.
" EUREKA is an experiment in how to attract, identify, and support particularly
creative approaches that, if successful, could move science forward dramatically," said
Jeremy M. Berg, Ph.D., director of the National
Institute of General Medical Sciences, which led the development of the
EUREKA program.
" EUREKA projects promise remarkable outcomes that could revolutionize
science," said NIH Director Elias A. Zerhouni, M.D. "The program
reflects NIH's commitment to supporting potentially transformative research,
even if it carries a greater than usual degree of scientific risk."
Argonne National Laboratory 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.
For more information, please contact Angela Hardin (630/252-5501
or ahardin@anl.gov) at Argonne.
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