Electron microscope close to imaging individual atoms

Chuck Bednar for redOrbit.com – @BednarChuck

A team of researchers from the US National Cancer Institute and the National Heart, Lung, and Blood Institute has developed an enhanced version of a cryo-electron microscope, meaning that these powerful tools for determining protein structures are more powerful than ever.

Cryo-electron microscopes (also known as cryo-EM) are used for analysis on the molecular or near-atomic level, and according to Science, the new one created by NCI structural biologist Dr. Sriram Subramaniam and his colleagues is the highest-resolution device of its kind to date.

The research team used their cryo-EM to create a new image that reveals a drug-like molecule bound to its protein at closer to atomic resolution than previously possible. The resolution is so sharp, the publication said, that it rivals the “gold standard” of mapping atomic protein contours, x-ray crystallography.

A tool in designing new and improved drugs

Cryo-EM shoots a beam of electrons at a thin film containing multiple copies of a protein that have been dipped in liquid nitrogen to freeze them in place. Detectors monitor the directions in which electrons scatter off different atoms in the protein, and when the images is taken, proteins are scattered in random orientations.

For this reason, scientists use imaging software to align their images of individual proteins into a common orientation, then use the electron scattering data to reconstruct the most likely position of the amino acids – and, if possible, its atoms. The technology has been around for decades, and has long been limited to a poorer resolution than x-ray crystallography and nuclear magnetic resonance (NMR) spectroscopy (0.5 nanometers vs. 0.2 nanometers).

In their new study, Dr. Subramaniam’s team took a protein that they had previously imaged at a resolution of 0.33 nanometers (β-galactosidase) and used some 40,000 separate images captured with their Cryo-EM to piece together the final shape of their molecule. With the device, they were able to produce an image at a resolution of 0.22 nanometers – not quite clear enough to see individual atoms, but good enough to see water molecules bind to the protein in key areas.

The development of such a powerful microscope should dramatically help pharmaceutical firms design novel drugs to treat a plethora of conditions, the journal noted, and National Institutes of Health head Francis Collins told Science that it would usher in “a new era” in imaging proteins in humans, and that the cryo-EM would have “immense implications for drug design.”

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