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Structure-based prediction of methyl chemical shifts in proteins

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Abstract

Protein methyl groups have recently been the subject of much attention in NMR spectroscopy because of the opportunities that they provide to obtain information about the structure and dynamics of proteins and protein complexes. With the advent of selective labeling schemes, methyl groups are particularly interesting in the context of chemical shift based protein structure determination, an approach that to date has exploited primarily the mapping between protein structures and backbone chemical shifts. In order to extend the scope of chemical shifts for structure determination, we present here the CH3Shift method of performing structure-based predictions of methyl chemical shifts. The terms considered in the predictions take account of ring current, magnetic anisotropy, electric field, rotameric type, and dihedral angle effects, which are considered in conjunction with polynomial functions of interatomic distances. We show that the CH3Shift method achieves an accuracy in the predictions that ranges from 0.133 to 0.198 ppm for 1H chemical shifts for Ala, Thr, Val, Leu and Ile methyl groups. We illustrate the use of the method by assessing the accuracy of side-chain structures in structural ensembles representing the dynamics of proteins.

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Acknowledgments

A.B.S. thanks Herchel Smith Foundation for the generous support. M.V. acknowledges the funding from the Leverhulme Trust, EMBO, the Royal Society and the BBSRC. W.F.V. was supported by the EU FP7 e-NMR grant 213010.

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  1. Wim F. Vranken

    Present address: Structural Biology Brussels, Vrije Universiteit Brussel, Pleinlaan 2, 1050, Brussels, Belgium

Authors and Affiliations

  1. Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge, CB2 1EW, UK

    Aleksandr B. Sahakyan, Andrea Cavalli & Michele Vendruscolo

  2. European Bioinformatics Institute, Wellcome Trust Genome Campus, Cambridge, CB10 1SD, UK

    Wim F. Vranken

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  1. Aleksandr B. Sahakyan
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  2. Wim F. Vranken
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  4. Michele Vendruscolo
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Correspondence to Michele Vendruscolo.

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Sahakyan, A.B., Vranken, W.F., Cavalli, A. et al. Structure-based prediction of methyl chemical shifts in proteins. J Biomol NMR 50, 331–346 (2011). https://doi.org/10.1007/s10858-011-9524-2

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