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The Phyre2 web portal for protein modeling, prediction and analysis

Nature Protocols volume 10, pages 845–858 (2015)Cite this article

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Abstract

Phyre2 is a suite of tools available on the web to predict and analyze protein structure, function and mutations. The focus of Phyre2 is to provide biologists with a simple and intuitive interface to state-of-the-art protein bioinformatics tools. Phyre2 replaces Phyre, the original version of the server for which we previously published a paper in Nature Protocols. In this updated protocol, we describe Phyre2, which uses advanced remote homology detection methods to build 3D models, predict ligand binding sites and analyze the effect of amino acid variants (e.g., nonsynonymous SNPs (nsSNPs)) for a user's protein sequence. Users are guided through results by a simple interface at a level of detail they determine. This protocol will guide users from submitting a protein sequence to interpreting the secondary and tertiary structure of their models, their domain composition and model quality. A range of additional available tools is described to find a protein structure in a genome, to submit large number of sequences at once and to automatically run weekly searches for proteins that are difficult to model. The server is available at http://www.sbg.bio.ic.ac.uk/phyre2. A typical structure prediction will be returned between 30 min and 2 h after submission.

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Figure 1: Normal mode Phyre2 pipeline showing algorithmic stages.
Figure 2: Intensive mode Phyre2 pipeline.
Figure 3: Phyre Investigator user interface.
Figure 4: Example Phyre2 summary results page.
Figure 5: Examples of the three main sections of a typical Phyre2 results page.
Figure 6: Example alignment between user query sequence and known structure, as described in Steps 25–28.

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Acknowledgements

This work was supported by the UK Biotechnology and Biological Sciences Research Council (L.A.K.: BB/J019240/1, M.N.W.: BB/F020481/1), the UK Medical Research Council (MRC) (C.M.Y.: MRC Standard Research Student (DTA) G1000390-1/1) and the UK Engineering and Physical Sciences Research Council (EPSRC) (S.M.: EPSRC Standard Research Student (DTG) EP/K502856/1).

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Author notes

  1. Christopher M Yates

    Present address: Present address: University College London (UCL) Cancer Institute, London, UK.,

  2. Mark N Wass

    Present address: Present address: Centre for Molecular Processing, School of Biosciences, University of Kent, Kent, UK.,

Authors and Affiliations

  1. Structural Bioinformatics Group, Imperial College London, London, UK

    Lawrence A Kelley, Stefans Mezulis, Christopher M Yates, Mark N Wass & Michael J E Sternberg

Authors
  1. Lawrence A Kelley
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  2. Stefans Mezulis
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  3. Christopher M Yates
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  4. Mark N Wass
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  5. Michael J E Sternberg
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Contributions

L.A.K. designed the Phyre2 system and wrote the paper; M.J.E.S. supervised the project; S.M. developed the multiple template modeling protocol; C.M.Y. developed the SuSPect method and M.N.W. developed the 3DLigandSite web resource.

Corresponding author

Correspondence to Lawrence A Kelley.

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Competing interests

M.J.E.S. is a director and shareholder in Equinox Pharma Ltd., which uses bioinformatics and chemoinformatics in drug discovery research and services.

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Kelley, L., Mezulis, S., Yates, C. et al. The Phyre2 web portal for protein modeling, prediction and analysis. Nat Protoc 10, 845–858 (2015). https://doi.org/10.1038/nprot.2015.053

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