Cited by 540Enzyme Structure and FunctionProtein Structure and DynamicsComputational Drug Discovery Methods

Crystal structure of a monomeric retroviral protease solved by protein folding game players

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Foldit Contenders Group, Khatib, Firas, Foldit Void Crushers Group, DiMaio, Frank, Cooper, Seth, Kazmierczyk, Maciej, Gilski, Miroslaw, Krzywda, Szymon +6 more·2011·Nature Structural & Molecular Biology

Abstract

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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Crossref · 10.1038/nsmb.2119

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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.”

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Research works printed but not linked: 11

  1. [1]Rohl CA Strauss CE Misura KM Baker D Methods Enzymol 2004 383 66 93 15063647
  2. [2]Cooper S Nature 2010 466 756 760 20686574 PMC2956414
  3. [3]Söding J Biegert A Lupas AN Nucleic Acids Res 2005 33 W244 W248 15980461 PMC1160169
  4. [4]Kinch L CASP9 assessment of free modeling target predictions Proteins in the press PMC3226891 21997521
  5. [5]MacCallum JL Assessment of protein structure refinement in CASP9 Proteins 30 8 2011 published online, doi:10.1002/prot.23131 PMC3238793 22069034 · DOI
  6. [6]Mastrolorenzo A Rusconi S Scozzafava A Barbaro G Supuran CT Curr. Med. Chem 2007 14 2734 2748 18045120
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  11. [11]McCoy AJ J. Appl. Cryst 2007 40 658 674 19461840 PMC2483472

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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
Venue
Nature Structural & Molecular Biology
Published
2011-09-18
Volume
18
Issue
10
Pages
1175-1177
ISSN
  • 1545-9985 (ISSN-L)
  • 1545-9993
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
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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