Conformational heterogeneity and probability distributions from single-particle cryo-electron microscopy

Wai Shing Tang, Ellen D. Zhong, Sonya M. Hanson, Erik H. Thiede, Pilar Cossio

Research output: Contribution to journalReview articlepeer-review

6 Scopus citations


Single-particle cryo-electron microscopy (cryo-EM) is a technique that takes projection images of biomolecules frozen at cryogenic temperatures. A major advantage of this technique is its ability to image single biomolecules in heterogeneous conformations. While this poses a challenge for data analysis, recent algorithmic advances have enabled the recovery of heterogeneous conformations from the noisy imaging data. Here, we review methods for the reconstruction and heterogeneity analysis of cryo-EM images, ranging from linear-transformation-based methods to nonlinear deep generative models. We overview the dimensionality-reduction techniques used in heterogeneous 3D reconstruction methods and specify what information each method can infer from the data. Then, we review the methods that use cryo-EM images to estimate probability distributions over conformations in reduced subspaces or predefined by atomistic simulations. We conclude with the ongoing challenges for the cryo-EM community.

Original languageEnglish (US)
Article number102626
JournalCurrent Opinion in Structural Biology
StatePublished - Aug 2023

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Structural Biology


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