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Protein structure prediction on the Web: a case study using the Phyre server

Abstract

Determining the structure and function of a novel protein is a cornerstone of many aspects of modern biology. Over the past decades, a number of computational tools for structure prediction have been developed. It is critical that the biological community is aware of such tools and is able to interpret their results in an informed way. This protocol provides a guide to interpreting the output of structure prediction servers in general and one such tool in particular, the protein homology/analogy recognition engine (Phyre). New profile–profile matching algorithms have improved structure prediction considerably in recent years. Although the performance of Phyre is typical of many structure prediction systems using such algorithms, all these systems can reliably detect up to twice as many remote homologies as standard sequence-profile searching. Phyre is widely used by the biological community, with >150 submissions per day, and provides a simple interface to results. Phyre takes 30 min to predict the structure of a 250-residue protein.

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Figure 1: Example of a typical Phyre results page.
Figure 2: Example of pseudomultiple sequence alignment from PSI-Blast.
Figure 3: Example of a typical Phyre alignment view.
Figure 4: Example of predicted functional sites colored by prediction confidence.

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Acknowledgements

L.A.K. is supported by the BBSRC grant number LDAD PO6300.

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Correspondence to Lawrence A Kelley.

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Sternberg is a director and shareholder of Equinox Pharma Ltd. And Dr. Kelley has in the past acted as a consultant for Equinox Pharma Ltd. The Phyre server and code is freely available to academics and is available to commercial users via a license from Equinox Pharma Ltd.

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Kelley, L., Sternberg, M. Protein structure prediction on the Web: a case study using the Phyre server. Nat Protoc 4, 363–371 (2009). https://doi.org/10.1038/nprot.2009.2

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