PreprintCited by 686Advanced Electron Microscopy Techniques and ApplicationsProtein Structure and DynamicsEnzyme Structure and Function

The DOI matches its Crossref record; 67 of the 72 references it cites were found in a registry or an index.

Automated model building and protein identification in cryo-EM maps

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Preprint — published as 10.1038/s41586-024-07215-4 · Paper page

Abstract

Interpreting electron cryo-microscopy (cryo-EM) maps with atomic models requires high levels of expertise and labour-intensive manual intervention. We present ModelAngelo, a machine-learning approach for automated atomic model building in cryo-EM maps. By combining information from the cryo-EM map with information from protein sequence and structure in a single graph neural network, ModelAngelo builds atomic models for proteins that are of similar quality as those generated by human experts. For nucleotides, ModelAngelo builds backbones with similar accuracy as humans. By using its predicted amino acid probabilities for each residue in hidden Markov model sequence searches, ModelAngelo outperforms human experts in the identification of proteins with unknown sequences. ModelAngelo will thus remove bottlenecks and increase objectivity in cryo-EM structure determination.

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Research works printed but not linked: 3

  1. 14. Lin, Z., et al. Language models of protein sequences at the scale of evolution enable accurate structure prediction. bioRxiv (2022). URL https://www.biorxiv.org/content/early/2022/07/21/2022.07.20.500902. https://www.biorxiv.org/content/early/2022/07/21/2022.07.20.500902.full.pdf.
  2. Jamali, K. , Kimanius, D. & Scheres, S. H . A graph neural network approach to automated model building in cryo-EM maps. In The Eleventh International Conference on Learning Representations (2023). URL https://openreview.net/forum?id=65XDF_nwI61.
  3. 2019, Macromolecular structure determination using x-rays, neutrons and electrons: recent developments in phenix, Acta Crystallographica Section D: Structural Biology, 75, 861, 10.1107/S2059798319011471 · DOI · Paper page

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Metadata

Authors
Jamali, K., Käll, L., Zhang, R., Brown, A., Kimanius, D., & Scheres, S. H. W.
Affiliations
  • MRC Laboratory of Molecular Biology (GB)
  • Science for Life Laboratory (SE)
  • Washington University in St. Louis (US)
  • Harvard University (US)
Corresponding author
  • Jamali, Kiarash
  • Kimanius, Dari
  • Scheres, Sjors H.W.
Venue
Nature
Publisher
openRxiv
Published
2023-05-16
Volume
628
Issue
8007
Pages
450-457
ISSN
0028-0836 (ISSN-L)
OpenAlex
W4392155415
Cited by
686
References
72
Citations by year
2026: 259 · 2025: 264 · 2024: 134 · 2023: 28
FWCI
120.08
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Nature (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Apollo (University of Cambridge) (acceptedVersion, cc-by)
  • PubMed Central (submittedVersion, cc-by)
  • Digital Commons@Becker (Washington University School of Medicine) (submittedVersion, cc-by)
  • RePEc: Research Papers in Economics (submittedVersion)
  • Zenodo (CERN European Organization for Nuclear Research) (submittedVersion, cc-by)
Funders
  • European Commission (HORIZON2020, 895412)
  • Knut och Alice Wallenbergs Stiftelse (2022.0032)
  • National Institutes of Health
  • Medical Research Council (MC_UP_A025_1013)
  • National Institute of General Medical Sciences (R01GM138854, R01GM141109)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Structural Biology › Advanced Electron Microscopy Techniques and Applications
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Structural Biology › Enzyme Structure and Function
Keywords
cryo-EM density maps, protein identification, graph neural networks, protein structure determination, machine learning

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