Ruth A. Mendonsa
The change of a single atom on a protein that regulates the molecular reading of our genetic code can trigger the onset of cancer. To learn how these and other molecular processes work, scientists study the three-dimensional atomic structures of protein molecules, and to examine a specific protein, they typically use x-ray crystallography. An advance in charge-coupled device (CCD) technology has made protein crystallography faster and more accurate.
The Detector Design Group at the Argonne National Laboratory's Structural Biology Center recently designed and built a detector of nine CCDs arranged in a 3 3 3 mosaic, featuring the 1024 3 1024-pixel CCDs from PixelVision/SITe. The new detector has a 186-sq-in. active area and is an integral part of a National User Facility for protein crystallography.
Smaller than a grain of salt
Before a specific protein can be studied, it must be isolated, purified and crystallized. Typically much smaller than a grain of salt, the crystals are highly ordered and, when irradiated with x-ray beams, scatter the x-rays into a diffraction pattern consisting of tens of thousands of closely spaced spots. The crystallographer must accurately measure the crystal's diffraction pattern to calculate the structure of the protein.
The advent of area-sensitive x-ray detectors based on CCDs eliminated the upper limit of x-ray intensity and offered high spatial resolution. But for crystallographic studies of protein structures, these single-module detectors were too small.
The new detectors, which are designed and built with multiple modules, use either front- or back-illuminated CCDs to provide large active imaging areas. They also offer high quantum efficiency and dynamic range. Because each module can be read out independently, parallel readout of multimodular detectors makes them fast.
'More than enough accuracy'
The director of the Structural Biology Center, Edwin Westbrook, said that the 24-µm pitch SITe chips feature low noise levels, allowing scientists to approach the point of sensing single x-ray photons. "These detectors permit us to measure diffraction spot intensities with uncertainties of about 2 percent," he said. "That's more than enough accuracy to perform the kind of crystallography we're doing."