Advances in structural biology have allowed scientists to determine molecular structures with atomic-level detail, sometimes yielding static snapshots that do not reflect the dynamism of proteins. However, these motions are often crucial for biological function. Researchers from the Institute of Science and Technology Austria (ISTA), together with international collaborators, have now combined several methods to shed light on how proteins “breathe” and how some experimental techniques freeze their motion. The findings—which could boost protein design approaches and improve AI-based structural prediction tools—are published in Nature Chemistry.

Despite serving as structural biology’s central pillar for more than half a century, protein crystallography has yielded static molecular structures—like still frames from a video—far from the buzzing life inside cells.

“How much can these ‘frozen snapshots’ of protein structures really tell us about their true biological functions and bustling molecular environments?” asks Lea Becker, the study’s first author and a Ph.D. student in Professor Paul Schanda’s group at the Institute of Science and Technology Austria (ISTA).