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Computational models in the service of X-ray and cryo-EM structure determination
  • +15
  • Andriy Kryshtafovych,
  • John Moult,
  • Reinhard Albrecht,
  • Geoffrey Chang,
  • Kinlin Chao,
  • Alec Fraser,
  • Julia Greenfield,
  • Marcus Hartmann,
  • Oznat Herzberg,
  • Inokentijs Josts,
  • Petr Leiman,
  • Sara Linden,
  • Andrei N. Lupas,
  • Daniel Nelson,
  • Steven Rees,
  • Xiaoran Shang,
  • Maria Sokolova,
  • Henning Tidow
Andriy Kryshtafovych
University of California Davis
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John Moult
University of Maryland Biotechnology Institute
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Reinhard Albrecht
Max Planck Institute for Developmental Biology
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Geoffrey Chang
University of California San Diego
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Kinlin Chao
University of Maryland Biotechnology Institute
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Alec Fraser
University of Texas Medical Branch at Galveston
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Julia Greenfield
University of Maryland Biotechnology Institute
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Marcus Hartmann
Max Planck Institute for Developmental Biology
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Oznat Herzberg
University of Maryland
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Inokentijs Josts
University of Hamburg
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Petr Leiman
University of Texas Medical Branch at Galveston
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Sara Linden
University of Maryland Biotechnology Institute
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Andrei N. Lupas
Max-Planck-Inst. for Developmental Biology
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Daniel Nelson
University of Maryland
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Steven Rees
University of California San Diego
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Xiaoran Shang
University of Maryland Biotechnology Institute
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Maria Sokolova
Skolkovo Institute of Science and Technology
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Henning Tidow
University of Hamburg
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Abstract

CASP (Critical Assessment of Structure prediction) conducts community experiments to determine the state of the art in computing protein structure from amino acid sequence. The process relies on the experimental community providing information about not yet public or about to be solved structures, for use as targets. For some targets, the experimental structure is not solved in time for use in CASP. Calculated structure accuracy improved dramatically in this round, implying that models should now be much more useful for resolving many sorts of experimental difficulty. To test this, selected models for seven unsolved targets were provided to the experimental groups. These models were from the AlphaFold2 group, who overall submitted the most accurate predictions in CASP14. Four targets were solved with the aid of the models, and, additionally, the structure of an already solved target was improved. An a-posteriori analysis showed that in some cases models from other groups would also be effective. This paper provides accounts of the successful application of models to structure determination, including molecular replacement for X-ray crystallography, backbone tracing and sequence positioning in a Cryo-EM structure, and correction of local features. The results suggest that in future there will be greatly increased synergy between computational and experimental approaches to structure determination.

Peer review status:ACCEPTED

07 May 2021Submitted to PROTEINS: Structure, Function, and Bioinformatics
08 May 2021Submission Checks Completed
08 May 2021Assigned to Editor
22 Jul 2021Reviewer(s) Assigned
06 Aug 2021Review(s) Completed, Editorial Evaluation Pending
06 Aug 2021Editorial Decision: Revise Minor
11 Aug 20211st Revision Received
13 Aug 2021Submission Checks Completed
13 Aug 2021Assigned to Editor
13 Aug 2021Reviewer(s) Assigned
14 Aug 2021Review(s) Completed, Editorial Evaluation Pending
17 Aug 2021Editorial Decision: Accept