Chemically accurate protein structures: Validation of protein NMR structures by comparison of measured and predicted pK a values
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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.
Key wordspKa structure validation ubiquitin
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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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