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Cited by 30Advanced Electron Microscopy Techniques and ApplicationsEnzyme Structure and FunctionProtein Structure and Dynamics

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Cryo-EM structure and B-factor refinement with ensemble representation

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Beton, Joseph G., Mulvaney, Thomas, Cragnolini, Tristan, Topf, Maya·2024·Nature Communications
DOI 10.1038/s41467-023-44593-1PMC PMC10781738

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Abstract

Cryo-EM experiments produce images of macromolecular assemblies that are combined to produce three-dimensional density maps. Typically, atomic models of the constituent molecules are fitted into these maps, followed by a density-guided refinement. We introduce TEMPy-ReFF, a method for atomic structure refinement in cryo-EM density maps. Our method represents atomic positions as components of a Gaussian mixture model, utilising their variances as B-factors, which are used to derive an ensemble description. Extensively tested on a substantial dataset of 229 cryo-EM maps from EMDB ranging in resolution from 2.1-4.9 Å with corresponding PDB and CERES atomic models, our results demonstrate that TEMPy-ReFF ensembles provide a superior representation of cryo-EM maps. On a single-model basis, it performs similarly to the CERES re-refinement protocol, although there are cases where it provides a better fit to the map. Furthermore, our method enables the creation of composite maps free of boundary artefacts. TEMPy-ReFF is useful for better interpretation of flexible structures, such as those involving RNA, DNA or ligands.

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Metadata

Authors
Beton, J. G., Mulvaney, T., Cragnolini, T., & Topf, M.
Affiliations
Leibniz Institute of Virology (LIV) (DE)
Corresponding author
Topf, Maya
ORCID
Venue
Nature Communications
Publisher
Springer Science and Business Media LLC
Published
2024-01-10
Volume
15
Issue
1
Pages
444-444
ISSN
2041-1723 (ISSN-L)
DOI
10.1038/s41467-023-44593-1
PMC
PMC10781738
OpenAlex
W4390708062
Cited by
30
References
6
Citations by year
2026: 12 · 2025: 15 · 2024: 2
FWCI
5.28
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Communications (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
  • DESY Publication Database (PUBDB) (Deutsches Elektronen-Synchrotron) (submittedVersion, other-oa)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • DESY Publication Database (PUBDB) (Deutsches Elektronen-Synchrotron)
Funders
  • Wellcome Trust (209250/Z/17/Z))
  • Leibniz-Gemeinschaft
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Structural Biology › Advanced Electron Microscopy Techniques and Applications
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Structural Biology › Enzyme Structure and Function
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
Keywords
cryo-EM density maps, Debye-Waller factor, Gaussian mixture model, ensemble representations, composite map
MeSH terms
Adenosine Monophosphate, Humans, RNA, Seizures, Normal Distribution, Artifacts, Cryoelectron Microscopy

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