For these reasons, X-ray facilities have sprung up around the country dedicated to crystallographic studies of proteins. The ALS - a particle accelerator called a synchrotron because it produces X-ray synchrotron radiation - upgraded in 2001 to become a cutting-edge source of high-energy or "hard" X-rays ideal for protein crystallography. At present, the ALS has six hard X-ray beamlines dedicated to X-ray crystallography, with two more in the works.
UC Berkeley and UC San Francisco together operate one beamline, managed by Holton, that in two years of operation has determined some 200 protein structures, 17 of which have been published. All told, only 30,000 protein structures are known out of the billions of proteins found in living organisms.
X-ray diffraction is a time-honored technique for determining the regular arrangement of atoms in a crystal. If a protein can be condensed into a solid crystal, high-energy X-rays will glance off the atoms and produce a distinctive pattern of reflections, like light shining through a faceted diamond. This pattern of bright spots is captured on film or CCD camera, so that scientists can calculate backward to reconstruct the crystal structure and thus the arrangement of atoms in the protein.
Elves is comprised of programs such as Wedger, Scaler, Phaser and Refmacer that automatically index the spots, locate heavy atoms in the protein, determine phase information through multi-wavelength anomalous dispersion, build a model, and just process the data or refine the model. No human intervention is needed as Elves tries different parameters.
"Computers are faster today and people are automating many steps in the process of analyzing X-ray diffraction data, and Elves combines all these techniques together," Holton said. "Making the crystal is 90 percent of the effort, but once you have that and you get the X-ray diffraction data, you're 19 minutes away from
Contact: Robert Sanders
University of California - Berkeley