Researchers from the U.S. Department of Energy’s (DOE) Lawrence Berkeley National Laboratory have developed a new process for determining the structure of proteins, which relies on an intense beam of light generated at the Advance Light Source (ALS) facility also on site - and shortens the typical time required to identify unknown biomolecules from years to just weeks.

“There’s a bottleneck in structural genomics, and our system addresses that,” says Greg Hura, a scientist in Berkeley Lab’s Physical Biosciences Division. He developed the technique with John Tainer of Berkeley Lab’s Life Sciences Division and the Scripps Research Institute in La Jolla, CA. Michael Adams and other scientists from the University of Georgia also contributed to the research.

Working with a beamline called, SIBYLS (Structurally Integrated BiologY for Life Sciences), the researchers use a technique called small angle x-ray scattering (SAXS), which can image a protein in its natural state, such as in a solution, and at a spatial resolution of about 10 angstroms, which is small enough to determine a protein’s three-dimensional shape. The brilliant light generated by the Advanced Light Source minimizes the amount of material required for each experiment, which makes the technique practical for almost any biomolecule.

To further maximize speed, the team utilized a robot that automatically pipettes samples into position so they can be analyzed by x-ray scattering. And to analyze the resulting data, they used the supercomputing resources of the U.S. Department of Energy’s National Energy Research Scientific Computing Center (NERSC), which is based at Berkeley Lab. The supercomputer's clusters can churn through data for 20 proteins per week, or more than 1000 macromolecules per year.

The result is a system that moves at breakneck speed compared to current techniques used to determine the shape and structure of proteins: x-ray crystallography and nuclear magnetic resonance. Recently, in the span of one month, the team used the system to resolve the structure of 40 proteins from Pyrococcus furiosus, a microscopic extremophile that can live at 100°C.

“This would have taken several years with x-ray crystallography,” says Hura. “What used to take years, now can take weeks.”

Adds Tainer, “We can now obtain structural information in solution on most samples, rather than the 15 percent obtained by the best of the current Structural Genomics Initiative efforts employing nuclear magnetic resonance and crystallography. “

A web version of the press release with images and video is available at: http://newscenter.lbl.gov/press-releases/2009/07/20/fast-protein-structu...