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Automated protein structure calculation from NMR data

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Abstract

Current software is almost at the stage to permit completely automatic structure determination of small proteins of <15 kDa, from NMR spectra to structure validation with minimal user interaction. This goal is welcome, as it makes structure calculation more objective and therefore more easily validated, without any loss in the quality of the structures generated. Moreover, it releases expert spectroscopists to carry out research that cannot be automated. It should not take much further effort to extend automation to ca 20 kDa. However, there are technological barriers to further automation, of which the biggest are identified as: routines for peak picking; adoption and sharing of a common framework for structure calculation, including the assembly of an automated and trusted package for structure validation; and sample preparation, particularly for larger proteins. These barriers should be the main target for development of methodology for protein structure determination, particularly by structural genomics consortia.

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Notes

  1. Plus of course it makes it harder to publish a new structure.

  2. The distribution of structures represented by an NMR ensemble is not (as one might expect) a representation of the true precision of the calculation. Rather, it is a representation of the reproducibility of the algorithm given the input data (Markwick et al. 2008). However, this is a subtlety that is easily overlooked.

  3. Kujira is Japanese for whale: a reference to the size and complexity of the program?

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Acknowledgments

We thank members of the Editorial Board of JBNMR for their helpful comments.

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  1. Department of Molecular Biology and Biotechnology, University of Sheffield, Firth Court, Western Bank, Sheffield, S10 2TN, UK

    Mike P. Williamson & C. Jeremy Craven

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Correspondence to Mike P. Williamson.

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Williamson, M.P., Craven, C.J. Automated protein structure calculation from NMR data. J Biomol NMR 43, 131–143 (2009). https://doi.org/10.1007/s10858-008-9295-6

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