A groundbreaking technique known as cryogenic electron microscopy or cryo-EM has been used by Arizona State University researchers in a new approach to studying molecules of life.
Examining not only their static structures at high resolution but the all-important dynamic movements of such molecules as they carry out biological functions, molecules targeted for study are flash-frozen in a thin membrane of ice before being subjected to electron microscopy.
Tens or even hundreds of thousands of still images are collected, then reassembled by means of computer.
The technique offers a powerful alternative to X-ray crystallography for probing the molecular world in keen detail.
Cryo-EM excels in the areas of study that are most challenging for X-ray crystallography, the imaging of large protein complexes resistant to conventional crystallization methods, Arizona State University explained in a statement.
Although early iterations of cryo-EM struggled to compete with the extreme image resolution characteristic of X-ray crystallography, rapid advances in the field now enable cryo-EM to produce stunning macromolecular images at near-atomic-resolution.
In the new study, Abhishek Singharoy and his colleagues at Arizona State University’s Biodesign Center for Applied Structural Discovery and School of Molecular Sciences demonstrate that cryo-EM can be pushed to even greater extremes of clarity, by extracting precious information previously buried in the reams of cryo-EM data.
“Now, we can actually see minimum free-energy pathways image-by-image during a simulation,” Singharoy said.
“It was impossible to see energetically feasible molecular movies before. Now cryo-EM, machine learning and molecular dynamics simulations have got us there.”