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Chemically accurate protein structures: Validation of protein NMR structures by comparison of measured and predicted pK a values

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Abstract

A new method is presented for evaluating the quality of protein structures obtained by NMR. This method exploits the dependence between measurable chemical properties of a protein, namely pK a values of acidic residues, and protein structure. The accurate and fast empirical computational method employed by the PROPKA program (http://www.propka.chem.uiowa.edu) allows the user to test the ability of a given structure to reproduce known pK a values, which in turn can be used as a criterion for the selection of more accurate structures. We demonstrate the feasibility of this novel idea for a series of proteins for which both␣NMR and X-ray structures, as well as pK a values of all ionizable residues, have been determined. For the 17 NMR ensembles used in this study, this criterion is shown effective in the elimination of a large number of NMR structure ensemble members.

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Acknowledgements

This work was supported by a grant from the National Science Foundation (MCB 209941). We thank Prof. Lawrence McIntosh for helpful suggestions on the manuscript.

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  1. Department of Chemistry, University of Iowa, Iowa City, USA

    N. Powers & Jan H. Jensen

  2. Department of Physics and Astronomy, University of Iowa, Iowa City, IA, 52242, USA

    N. Powers

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Correspondence to Jan H. Jensen.

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Powers, N., Jensen, J. Chemically accurate protein structures: Validation of protein NMR structures by comparison of measured and predicted pK a values. J Biomol NMR 35, 39–51 (2006). https://doi.org/10.1007/s10858-006-9003-3

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