Seminars Archive

From Snapshots to Motion: Visualizing Protein Dynamics with Cryo-EM

Alfredo De Biasio
King Abdullah University of Science and Technology - Saudi Arabia

Abstract
Life depends on molecular machines that move-polymerases copying DNA, helicases unwinding it, ribosomes translating RNA. Yet most of our knowledge comes from static structures, like photos of dancers frozen mid-step. What we really need is the choreography: how molecules shift from one state to another, and how these motions drive function. Cryo-electron microscopy (cryo-EM), awarded the 2017 Nobel Prize in Chemistry, is now being used not only to determine static structures but also to capture motion. By analyzing the natural variability in cryo-EM data, we can extract trajectories of molecular movement. Using the SV40 Large T-antigen helicase as an example, I will show how particle variability analysis (3DVA) reveals DNA being translocated step by step during ATP hydrolysis [1]. These results challenge the classical "power stroke" model and suggest that enzymes harness thermal fluctuations, with ATP hydrolysis acting as a switch to bias motion forward.

[1] https://www.nature.com/articles/s41586-025-08766-w