Crystal structure of a monomeric retroviral protease solved by protein folding game players
Open accessAbstract
Following the failure of a wide range of attempts to solve the crystal structure of M-PMV retroviral protease by molecular replacement, we challenged players of the protein folding game Foldit to produce accurate models of the protein. Remarkably, Foldit players were able to generate models of sufficient quality for successful molecular replacement and subsequent structure determination. The refined structure provides new insights for the design of antiretroviral drugs.
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It is now potentially possible to obtain complete structure solutions using Foldit given only a native crystallography data set, combined with the ability to generate molecular replacement solutions in Foldit and therefore circumvent the need for experimental phases in some cases.
“Combined with the ability to generate molecular replacement solutions in Foldit, and therefore to circumvent the need for experimental phases in some cases14, it is now potentially possible to obtain complete structure solutions using Foldit given only a native crystallography data set.”
From Determining crystal structures through crowdsourcing and coursework (2016) · cites this paper as [14]
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<i>Phaser</i> crystallographic software
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Boyd, P. W., Rynearson, T. A., Armstrong, E. A., Fu, F., Hayashi, K., Hu, Z., Hutchins, D. A., Kudela, R. M., Litchman, E., Mulholland, M. R., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0063091 · Cited by 429 · see citing works
Peer and self assessment in massive online classes
Kulkarni, C., Wei, K. P., Le, H., Chia, D., Papadopoulos, K., Cheng, J., Koller, D., & Klemmer, S. R. (2013) · ACM Transactions on Computer-Human Interaction · doi:10.1145/2505057 · Cited by 390 · see citing works
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Determining crystal structures through crowdsourcing and coursework
Horowitz, S., Koepnick, B., Martin, R., Tymieniecki, A., Winburn, A. A., Cooper, S., Flatten, J., Rogawski, D. S., Koropatkin, N. M., Hailu, T. T., et al. (2016) · Nature Communications · doi:10.1038/ncomms12549 · Cited by 75 · see citing works
Self-citationScientific rigor through videogames
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- Authors
- Foldit Contenders Group, Khatib, F., Foldit Void Crushers Group, DiMaio, F., Cooper, S., Kazmierczyk, M., Gilski, M., Krzywda, S., Zabranska, H., Pichova, I., Thompson, J., Popović, Z., Jaskolski, M., & Baker, D.
- Affiliations
- University of Washington (US)
- Adam Mickiewicz University in Poznań (PL)
- Czech Academy of Sciences, Institute of Organic Chemistry and Biochemistry (CZ)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Baker, David
- ORCID
- Venue
- Nature Structural & Molecular Biology
- Published
- 2011-09-18
- Volume
- 18
- Issue
- 10
- Pages
- 1175-1177
- ISSN
- 1545-9985 (ISSN-L)
- 1545-9993
- PMC
- PMC3705907
- OpenAlex
- W1992145496
- Cited by
- 540
- References
- 1
- Citations by year
- 2026: 3 · 2025: 8 · 2024: 27 · 2023: 16 · 2022: 13 · 2021: 29 · 2020: 21 · 2019: 33 · 2018: 50 · 2017: 40 · 2016: 56 · 2015: 65 · 2014: 59 · 2013: 65 · 2012: 42
- FWCI
- 26.38
- Type
- journal article
- Language
- en
- Update notices
- erratum (2012-03-05)
- Open access
- green
- europepmc.org
- Locations
- Nature Structural & Molecular Biology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- ASEP (submittedVersion, public-domain)
- Desy publication database (The Deutsches Elektronen-Synchrotron) (submittedVersion, other-oa)
- Funders
- National Science Foundation
- Howard Hughes Medical Institute
- Microsoft
- Defense Advanced Research Projects Agency
- National Institute of General Medical Sciences (R01GM092802)
- Topics
- Physical Sciences › Materials Science › Materials Chemistry › Enzyme Structure and Function
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Physical Sciences › Computer Science › Computational Theory and Mathematics › Computational Drug Discovery Methods
- Keywords
- retroviral protease, crystal structure determination, Foldit, protein structure prediction, molecular replacement, antiretroviral drug design
- MeSH terms
- Models, Molecular, Peptide Hydrolases, Protein Conformation, Retroviridae, Viral Proteins, Protein Folding, Crystallography, X-Ray
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