X-Ray Scattering Aids New-Drug Search

Researchers have used wide-angle x-ray scattering (WAXS) to study protein-ligand binding and suggest that this technique may prove to be a reliable and high-speed tool for identification of potential new drugs.

Investigators at the Argonne National Laboratory (IL, USA) adapted WAXS technology, usually used in the materials sciences, to study ligand-induced structural changes in proteins. The method is similar to x-ray crystallography but does not require crystallization of the protein. Instead, the protein and ligand are dissolved in an aqueous medium. This is then placed in the path of the x-ray beam, and the scattering pattern for the protein-ligand complex is compared to the pattern demonstrated by the protein alone.

This method allows researchers to determine whether the interaction between the protein and ligand causes changes in the structure of the protein. A ligand that causes structural changes has greater potential as a drug candidate.

"Wide angle x-ray scattering provides a real tool for identifying lead drugs,” said senior author Dr. Lee Makowski, senior investigator in the biosciences division of the Argonne National Laboratory. "It will identify a molecule that is good enough to be developed as a drug. The data collection only takes a couple of minutes, so theoretically an industrial pipeline could be set up that would only be limited by a few minutes per protein-small molecule interaction. Functional cell-based assays currently take weeks, if not months to complete--causing a bottleneck in data collection and analysis.”




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Argonne National Laboratory