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CASP15 cryoEM protein and RNA targets: refinement and analysis using experimental maps
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  • Thomas Mulvaney,
  • Rachael C. Kretsch,
  • Luc Elliott,
  • Joe Beton,
  • Andriy Kryshtafovych,
  • Daniel Rigden,
  • Rhiju Das,
  • Maya Topf
Thomas Mulvaney
Leibniz-Institut fur Virologie
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Rachael C. Kretsch
Stanford University
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Luc Elliott
University of Liverpool
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Joe Beton
Leibniz-Institut fur Virologie
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Andriy Kryshtafovych
University of California Davis Genome Center
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Daniel Rigden
University of Liverpool
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Rhiju Das
Stanford University
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Maya Topf
Leibniz-Institut fur Virologie

Corresponding Author:[email protected]

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CASP assessments primarily rely on comparing predicted coordinates with experimental reference structures. However, errors in the reference structures can potentially reduce the accuracy of the assessment. This issue is particularly prominent in cryoEM-determined structures, and therefore, in the assessment of CASP15 cryoEM targets, we directly utilized density maps to evaluate the predictions. A method for ranking the quality of protein chain predictions based on rigid fitting to experimental density was found to correlate well with the CASP assessment scores. Overall, the evaluation against the density map indicated that the models are of high accuracy although local assessment of predicted side chains in a 1.52 Å resolution map showed that side-chains are sometimes poorly positioned. The top 136 predictions associated with 9 protein target reference structures were selected for refinement, in addition to the top 40 predictions for 11 RNA targets. To this end, we have developed an automated hierarchical refinement pipeline in cryoEM maps. For both proteins and RNA, the refinement of CASP15 predictions resulted in structures that are close to the reference target structure, including some regions with better fit to the density. This refinement was successful despite large conformational changes and secondary structure element movements often being required, suggesting that predictions from CASP-assessed methods could serve as a good starting point for building atomic models in cryoEM maps for both proteins and RNA. Loop modeling continued to pose a challenge for predictors with even short loops failing to be accurately modeled or refined at times. The lack of consensus amongst models suggests that modeling holds the potential for identifying more flexible regions within the structure.
22 Jun 2023Submitted to PROTEINS: Structure, Function, and Bioinformatics
22 Jun 2023Submission Checks Completed
22 Jun 2023Assigned to Editor
22 Jun 2023Review(s) Completed, Editorial Evaluation Pending
27 Jun 2023Reviewer(s) Assigned
31 Jul 2023Editorial Decision: Revise Major
26 Oct 20231st Revision Received
26 Oct 2023Submission Checks Completed
26 Oct 2023Assigned to Editor
26 Oct 2023Review(s) Completed, Editorial Evaluation Pending
26 Oct 2023Reviewer(s) Assigned
10 Nov 2023Editorial Decision: Accept