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EC-BLAST: a tool to automatically search and compare enzyme reactions

Nature Methods volume 11, pages 171174 (2014) | Download Citation

Abstract

We present EC-BLAST (http://www.ebi.ac.uk/thornton-srv/software/rbl/), an algorithm and Web tool for quantitative similarity searches between enzyme reactions at three levels: bond change, reaction center and reaction structure similarity. It uses bond changes and reaction patterns for all known biochemical reactions derived from atom-atom mapping across each reaction. EC-BLAST has the potential to improve enzyme classification, identify previously uncharacterized or new biochemical transformations, improve the assignment of enzyme function to sequences, and assist in enzyme engineering.

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Acknowledgements

S.A.R., S.M.C. and G.L.H. acknowledge funding from the EMBL. N.F. and S.A.R. acknowledge funding from the Wellcome Trust (grant no. 081989/Z/07/A). We thank L. Baldacci, F. Fenninger, G. Torrance, S. Choudhary, N. Gopal, and S.T. Williams for their technical contributions. We thank D. Schomburg, J. Mitchell and C. Steinbeck for their support; the IUBMB-EC commission for their support and encouragement; J. May for improving the stereo detection library; and E. Willighagen and other Chemistry Development Kit (CDK) developers for helping out with the CDK library and timely review of the patches.

Author information

Author notes

    • Nicholas Furnham
    •  & Gemma L Holliday

    Present addresses: Department of Pathogen Molecular Biology, London School of Hygiene & Tropical Medicine, London, UK (N.F.) Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, California, USA (G.L.H.).

Affiliations

  1. European Molecular Biology Laboratory–European Bioinformatics Institute (EMBL-EBI), Wellcome Trust Genome Campus, Hinxton, UK.

    • Syed Asad Rahman
    • , Sergio Martinez Cuesta
    • , Nicholas Furnham
    • , Gemma L Holliday
    •  & Janet M Thornton

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Contributions

S.A.R. developed the algorithm, code and the EC-BLAST tool. S.A.R. and J.M.T. wrote the majority of the manuscript and performed the statistical analysis. S.M.C. and G.L.H. were involved in curating the molecules, testing the chemical validity of the reaction similarity clusters and helping in the manuscript write up. S.A.R. and N.F. performed the analysis of the PPI family and the write-up. J.M.T. supervised the whole project and the manuscript write-up.

Competing interests

The authors declare no competing financial interests.

Corresponding authors

Correspondence to Syed Asad Rahman or Janet M Thornton.

Supplementary information

PDF files

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    Supplementary Text and Figures

    Supplementary Figures 1–3, Supplementary Tables 1–3, Supplementary Results and Supplementary Notes 1 and 2

Zip files

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    Supplementary Data 1

    Source raw data for Figure 2 containing similarity scores between EC-Reactions, cluster information, etc.

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    Supplementary Data 2

    Source data for Supplementary Figure 1

  2. 2.

    Supplementary Data 3

    Source data for Supplementary Figure 2

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DOI

https://doi.org/10.1038/nmeth.2803

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