Argonne scientists use lasers to align
molecules
Technique could revolutionize human protein imaging
Protein crystallographers have only scratched the surface of the human
proteins important for drug interactions because of difficulties crystallizing
the molecules for synchrotron X-ray diffraction. Now scientists at the U.S.
Department of Energy's (DOE) Argonne National Laboratory have devised a way to
eliminate the need for crystallization by using lasers to align large groups of
molecules.
"Strong laser fields can be used to control the behavior of atoms and
molecules," Argonne
Distinguished Fellow Linda Young said. "Using X-rays, we can investigate
their properties in a totally new way."
Crystallization allows scientists to create a periodic structure that will
strongly diffract in specific directions when bombarded with X-rays. From the
resulting diffraction pattern, scientists can construct a real-space image of
the crystal. However, without crystallization, when X-rays collide with
multiple, randomly oriented molecules, they diffract in different directions,
making it impossible to create a composite diffraction image, said Argonne
Physicist Robin Santra.
Some molecules, such as many involved with drug interaction, cannot be
crystallized, and imaging would require numerous samples to bombard in order to
get a full composite picture. Young's laser technique allows for millions of
molecules suspended in a gaseous state to be aligned so that, when bombarded
with X-rays, they all diffract in the same way. The resulting images are at
atomic level resolution and do not require crystallization.
"Understanding the structure of the approximately 1 million human proteins
that cannot be crystallized is perhaps the most important challenge facing
structural biology," Young said. "A method for structure determination at atomic
resolution without the need to crystallize would be revolutionary."
Young and her team have successfully aligned molecules using a laser, probed
the aligned ensemble with X-rays and shown theoretically that the technique
could be used for X-ray imaging – see E. R. Peterson et al.,
Applied Physics Letters 92,
094106 (2008) – but they require a proposed upgrade to the
Advanced Photon Source facility located at
Argonne before X-ray diffraction can be done experimentally.
Funding for this research was provided by the
U.S. Department of Energy,
Office of Science,
Basic Energy Sciences,
Chemical
Sciences, Geosciences, and Biosciences, and by the
Alexander von Humboldt Foundation, Bonn, Germany. The mission of the Basic Energy Sciences program – a multipurpose, scientific
research effort – is to foster and support fundamental research to expand the
scientific foundations for new and improved energy technologies and for
understanding and mitigating the environmental impacts of energy use. The
portfolio supports work in the natural sciences, emphasizing fundamental
research in materials sciences, chemistry, geosciences, and aspects of
biosciences.
Argonne National Laboratory News Release, May 13, 2008 |