Disentangling Conformational States of Macromolecules in 3D-EM Through Likelihood Optimization

Nat Methods. 2007 Jan;4(1):27-9. doi: 10.1038/nmeth992. Epub 2006 Dec 10.


Although three-dimensional electron microscopy (3D-EM) permits structural characterization of macromolecular assemblies in distinct functional states, the inability to classify projections from structurally heterogeneous samples has severely limited its application. We present a maximum likelihood-based classification method that does not depend on prior knowledge about the structural variability, and demonstrate its effectiveness for two macromolecular assemblies with different types of conformational variability: the Escherichia coli ribosome and Simian virus 40 (SV40) large T-antigen.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, Polyomavirus Transforming / chemistry*
  • Escherichia coli / chemistry
  • Image Processing, Computer-Assisted / methods*
  • Imaging, Three-Dimensional / methods*
  • Likelihood Functions
  • Microscopy, Electron / methods*
  • Models, Molecular
  • Protein Conformation
  • Ribosomes / chemistry*
  • Sensitivity and Specificity
  • Simian virus 40 / chemistry


  • Antigens, Polyomavirus Transforming