Summary
Counting particles collected with cryo-EM does not reliably provide the true Boltzmann distributions of protein structures (1). In contrast, directly solving the inverse problem provides a more accurate estimate. This was shown using synthetic datasets of the SARS-CoV-2 spike protein and an IgG1 antibody.
See also
1.
Evans L, Dingeldein L, Covino R, Gilles MA, Thiede E, Cossio P. Counting particles could give wrong probabilities in Cryo-Electron Microscopy. openRxiv; 2025. Available from: https://doi.org/10.1101/2025.03.27.644168