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An R-Based Landscape Validation of a Competing Risk Model
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Validating Resolution Revolution.

Piotr Neumann1, Achim Dickmanns1, Ralf Ficner1

  • 1Department of Molecular Structural Biology, Institute of Microbiology & Genetics, GZMB, Georg-August-University Göttingen, Justus-von-Liebig-Weg 11, 37077 Göttingen, Germany.

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Summary

A new validation method for cryo-electron microscopy (cryo-EM) reveals that most structures have poor agreement between the map and model. This highlights the need to re-evaluate cryo-EM map resolution and standards.

Keywords:
FSCFSC-based validationRSCC-based validationcryo-EMestimation of resolutionquality criteriavalidation

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Area of Science:

  • Structural Biology
  • Biophysics
  • Biochemistry

Background:

  • Cryo-electron microscopy (cryo-EM) has advanced significantly, leading to a resolution revolution and increased popularity.
  • Despite progress, standards for assessing cryo-EM map and model agreement are lacking.

Purpose of the Study:

  • To establish a validation procedure for evaluating the agreement between cryo-EM maps and their corresponding models.
  • To assess the quality of existing cryo-EM structures based on map-model agreement.

Main Methods:

  • Developed and applied a novel validation procedure to 565 cryo-EM structures.
  • Analyzed the agreement between cryo-EM maps and atomic models.
  • Evaluated the impact of model re-refinement on map-model agreement.

Main Results:

  • Three-quarters of the analyzed cryo-EM structures showed moderate or low map-model agreement.
  • Limited structural features in maps were the primary cause of poor agreement.
  • Model re-refinement improved agreement in only 20% of structures.

Conclusions:

  • Current cryo-EM structures often exhibit suboptimal agreement between maps and models.
  • The developed procedure can help re-estimate cryo-EM map resolution.
  • There is a critical need for improved validation standards in cryo-EM structural biology.