New computational method pushes cryo-electron microscopy beyond traditional resolution limits

Cryo-electron microscopy (cryo-EM) has revolutionized the determination of protein, virus, and molecular complex structures at near-atomic resolution. However, its resolution is capped by the Nyquist sampling frequency, which hinges on detector pixel size and microscope magnification. Once this limit is hit, scientists often need to re-acquire data at higher magnifications, consuming more microscope time, storage space, and yielding fewer particles per image.

A team from the Exploratory Research Center on Life and Living Systems and the National Institute for Physiological Sciences has now introduced a computational technique called Post-Acquisition Super Resolution (PASR). PASR enhances cryo-EM datasets to surpass traditional Nyquist limits post-data collection. It functions by dividing detector pixels computationally before motion correction, thereby capturing subtle particle motion between movie frames to unveil higher-frequency structural details.

The research, published in the journal IUCrJ, demonstrates PASR’s effectiveness across various datasets, including apoferritin, adeno-associated virus, jack bean urease, and the giant virus Melbournevirus. Utilizing standard cryo-EM software like RELION and CryoSPARC, PASR significantly improves map quality and resolution, all without introducing artifacts.

This methodology could potentially cut down microscope usage time and data storage requirements, while also benefiting the analysis of large, flexible, or heterogeneous biological entities.

Raymond N. Burton Smith et al. detailed their findings in the paper titled "Post-acquisition super resolution for cryo-electron microscopy," which is now accessible through the DOI: 10.1107/s2052252526005348.