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 in cryo-electron microscopy may result in incorrect population estimates. Communications Biology. 2026;9(1):421. Available from: https://doi.org/10.1038/s42003-026-09859-6