Crystallographic molecular replacement using an in silico‐generated search model of SARS‐CoV‐2 ORF8
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Abstract
The majority of crystal structures are determined by the method of molecular replacement (MR). The range of application of MR is limited mainly by the need for an accurate search model. In most cases, pre‐existing experimentally determined structures are used as search models. In favorable cases, ab initio predicted structures have yielded search models adequate for MR. The ORF8 protein of SARS‐CoV‐2 represents a challenging case for MR using an ab initio prediction because ORF8 has an all β‐sheet fold and few orthologs. We previously determined experimentally the structure of ORF8 using the single anomalous dispersion (SAD) phasing method, having been unable to find an MR solution to the crystallographic phase problem. Following a report of an accurate prediction of the ORF8 structure, we assessed whether the predicted model would have succeeded as an MR search model. A phase problem solution was found, and the resulting structure was refined, yielding structural parameters equivalent to the original experimental solution.
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- Authors
- Flower, T. G., & Hurley, J. H.
- Affiliations
- QB3 (US)
- Corresponding author
- Hurley, James H.
- Venue
- Protein Science
- Publisher
- Wiley
- Published
- 2021-03-04
- Volume
- 30
- Issue
- 4
- Pages
- 728-734
- ISSN
- 0961-8368 (ISSN-L)
- 1469-896X
- PMC
- PMC7980513
- OpenAlex
- W3130686756
- Cited by
- 49
- References
- 31
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 5 · 2023: 16 · 2022: 17 · 2021: 8
- FWCI
- 3.49
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Protein Science (publishedVersion)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (submittedVersion, cc-by-nc-nd)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Institute of Allergy and Infectious Diseases (R37 AI112442)
- National Institutes of Health
- Office of the President, University of California (R00RG2347)
- Topics
- Physical Sciences › Materials Science › Materials Chemistry › Enzyme Structure and Function
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Keywords
- ab initio structure prediction, phase problem, protein structure determination
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