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Completeness in structural genomics

Nature Structural Biology volume 8, pages 559–566 (2001)Cite this article

Abstract

Structural genomics has the goal of obtaining useful, three-dimensional models of all proteins by a combination of experimental structure determination and comparative model building. We evaluate different strategies for optimizing information return on effort. The strategy that maximizes structural coverage requires about seven times fewer structure determinations compared with the strategy in which targets are selected at random. With a choice of reasonable model quality and the goal of 90% coverage, we extrapolate the estimate of the total effort of structural genomics. It would take ∼16,000 carefully selected structure determinations to construct useful atomic models for the vast majority of all proteins. In practice, unless there is global coordination of target selection, the total effort will likely increase by a factor of three. The task can be accomplished within a decade provided that selection of targets is highly coordinated and significant funding is available.

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Figure 1: Accuracy of CASP protein structure models as a function of target-template sequence identity.
Figure 2: Current structural coverage of proteins in SP + TrEMBL.
Figure 3: Structural coverage of a protein family, illustrated using the Ras family in yeast as an example.
Figure 4: Scope of structural coverage as a function of model quality.
Figure 5: Two factors affecting the scale of structural genomics.

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Acknowledgements

We thank L. Holm, D. Marks and J. Norvell for discussions and C. Venclosas for providing CASP template/target sequence identity data. This work was supported in part by research grants from the US National Institute of Health (NIGMS) and the Department of Energy to J.M. and C.S.

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Authors and Affiliations

  1. MIT Center for Genome Research, One Kendall Square, Building 300, Cambridge, 02139, Massachusetts, USA

    Dennis Vitkup & Chris Sander

  2. Department of Chemistry and Chemical Biology, Harvard University, Cambridge, 02138, Massachusetts, USA

    Dennis Vitkup

  3. Center for Advanced Research in Biotechnology, University of Maryland Biotechnology Institute, 9600 Gudelsky Drive, Rockville, 20850, Maryland, USA

    Eugene Melamud & John Moult

  4. Millennium Pharmaceuticals, 640 Memorial Drive, Cambridge, 02139, Massachusetts, USA

    Chris Sander

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Correspondence to Chris Sander.

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Vitkup, D., Melamud, E., Moult, J. et al. Completeness in structural genomics. Nat Struct Mol Biol 8, 559–566 (2001). https://doi.org/10.1038/88640

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