Gigantic Ruler to Measure Tiny Distances

Scientists at Argonne National Lab have received a grant from the NIH to utilize the power of the Advanced Photon Source, one of the world’s most powerful emitters of X-rays, to develop a system to precisely measure atomic distances within protein structures.

MADMAX, which stands for the Multi-wavelength Anomalous Diffraction using Medium Angle X-ray solution scattering, would not only dramatically reduce the time necessary to reveal the behaviors of a protein, but could provide a new tool for pharmaceutical companies developing new drugs such as protease inhibitors for the treatment of HIV. It could also be a stark improvement to the decades-old method of crystallizing proteins, which could involve the use of harsh chemicals and can show how a protein is structured but often provides precious few clues as to how it moves in nature.
“There’s almost nothing that a protein does that doesn’t involve some movement,” said Lee Makowski, principal investigator of the project. “Proteins have to move, and understanding that movement is key to figuring out how the proteins work.”
MADMAX will precisely measure the inter-atomic distances between different parts of proteins in a solution by using selenium to ‘tag’ the proteins so the labels can be detected via the X-ray scattering. The selenium is easily incorporated into proteins, allowing for their study while not interfering with their function.
The proteins in solution are then hit with a beam of X-rays, and the scattering is used to determine the distances between selenium atoms in the protein. When the protein moves, the distances change and the movements of the protein can be measured with great accuracy.
“If successful, MADMAX would change how we study proteins and protein motion,” Makowski said. “That’s a huge thing.”
MADMAX would allow scientists to see how a protein changes as a result of its environment, observe how ligands bind to a proteins’ surface and follow the process of protein or RNA folding. It would also give pharmaceutical companies the chance to observe how their drugs interact with proteins, potentially saving time and expenses by providing them with unique insight into the mechanism of the drugs’ action.

Press release: Precise molecular ruler could play role in development of new drugs…
Image: Aerial view of the Advanced Photon Source