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Jet-propelled imaging for an ultrafast light source
Date:7/29/2009

protein's atoms is therefore a great help to drug designers, who like to understand how a drug molecule will dock with a protein to promote or inhibit its activity, or cripple the organism of which it is a part.

Until now, the best way to solve the structure of a protein or virus has been with x-ray crystallography. The crystal consists of many copies of the protein or virus arranged in regular order. As the crystal rotates in the x-ray beam, x-rays scatter off the atoms and reveal once these complex diffraction patterns have been converted into a 3-D image by computers how the electrons, and thus the atoms, are arranged.

But many proteins can't be crystallized at all, and others are so difficult to crystallize it's virtually impossible to obtain crystals large enough to use in today's light sources.

Ultrafast, ultrabright x-rays offer a way past this dilemma. The idea is that a quick pulse of tightly focused x-rays can be diffracted from a microcrystal or even a single protein or virus in solution. The pulse is so brief that it comes and goes before any of the atoms can move, freezing their orientation like a strobe light. Just as important, a sufficiently brief pulse may terminate before radiation damage effects can start. In this way it can outrun radiation damage, always one of the fundamental limitations to imaging in biology.

Another quick pulse could be diffracted from another copy of the protein in a different orientation. As the process is repeated, diffractions from different angles give the overlapping views needed for the computer to construct a 3-D image of the structure.

It's a great idea, but as Spence notes, there are a few problems. "So as not to scatter, the x-ray beam has to be in a high vacuum, but a protein or virus in its natural state is usually wet. As in T. S. Eliot's Wasteland, water is life. How do we maintain the protein or virus in an aqueous environment inside the vacuum?"


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Contact: Paul Preuss
paul_preuss@lbl.gov
510-486-6249
DOE/Lawrence Berkeley National Laboratory
Source:Eurekalert  

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