A Faster Way to Image Protein Structures

At the Lawrence Berkeley National Laboratory’s Advanced Light Source scientists have come up with a new method to identify the structure of proteins. By using the lab’s powerful X-ray source, they implemented small angle x-ray scattering (SAXS) to map out the 3D structure of proteins faster than ever before. The technique has lead to an automated process that can go through thousands of different proteins.

To maximize speed, Hura installed a robot that automatically pipettes protein 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.
The Berkeley Lab team chose P. furiosus because it is an intriguing candidate for the production of clean energy and other applications. It has a pathway that produces hydrogen, which is a potential alternative fuel. And many industrial processes are highly acidic and very hot — conditions that P. furiosus loves.
Of course, such speed doesn’t come without tradeoffs. X-ray crystallography yields extremely high-resolution images, while small angle x-ray scattering yields a protein’s shape at a much lower resolution of about 10 angstroms (one angstrom is one ten-millionth of a millimeter).
But the level of information offered by x-ray crystallography isn’t always necessary. Sometimes, simply knowing if one protein is similar in shape to another is enough to learn its function. And SAXS makes up for what it lacks in precision by providing accurate information on the shape, assembly, and conformational changes of proteins in solution.