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On the use of time-averaging restraints when deriving biomolecular structure from \(^3J\)-coupling values obtained from NMR experiments

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Abstract

Deriving molecular structure from \(^3J\)-couplings obtained from NMR experiments is a challenge due to (1) the uncertainty in the Karplus relation \(^3J(\theta )\) connecting a \(^3J\)-coupling value to a torsional angle \(\theta \), (2) the need to account for the averaging inherent to the measurement of \(^3J\)-couplings, and (3) the sampling road blocks that may emerge due to the multiple-valuedness of the inverse function \(\theta (^3J)\) of the function \(^3J(\theta )\). Ways to properly handle these issues in structure refinement of biomolecules are discussed and illustrated using the protein hen egg white lysozyme as example.

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Acknowledgments

L.J.S. would like to acknowledge the use of the University of Oxford Advanced Research Computing (ARC) facility in carrying out some of this work. http://dx.doi.org/10.5281/zenodo.22558. W.F.vG. thanks the Swiss National Science Foundation, Grant Number 200020-137827, and the European Research Council, Grant Number 228076, for financial support. N.H. thanks the German Research Foundation (DFG) for financial support within the Cluster of Excellence in Simulation Technology (EXC 310/2) at the University of Stuttgart.

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Authors and Affiliations

  1. Inorganic Chemistry Laboratory, Department of Chemistry, University of Oxford, South Parks Road, Oxford, OX1 3QR, UK

    Lorna J. Smith

  2. Laboratory of Physical Chemistry, Swiss Federal Institute of Technology, ETH, 8093, Zurich, Switzerland

    Wilfred F. van Gunsteren

  3. Institute of Thermodynamics and Thermal Process Engineering, University of Stuttgart, 70569, Stuttgart, Germany

    Niels Hansen

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  1. Lorna J. Smith
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  3. Niels Hansen
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Correspondence to Niels Hansen.

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Smith, L.J., van Gunsteren, W.F. & Hansen, N. On the use of time-averaging restraints when deriving biomolecular structure from \(^3J\)-coupling values obtained from NMR experiments. J Biomol NMR 66, 69–83 (2016). https://doi.org/10.1007/s10858-016-0058-5

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