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Structure of hen egg-white lysozyme solvated in TFE/water: a molecular dynamics simulation study based on NMR data

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Abstract

Various experimental studies of hen egg white lysozyme (HEWL) in water and TFE/water clearly indicate structural differences between the native state and TFE state of HEWL, e.g. the helical content of the protein in the TFE state is much higher than in the native state. However, the available detailed NMR studies were not sufficient to determine fully a structure of HEWL in the TFE state. Different molecular dynamics (MD) simulations, i.e. at room temperature, at increased temperature and using proton–proton distance restraints derived from NMR NOE data, have been used to generate configurational ensembles corresponding to the TFE state of HEWL. The configurational ensemble obtained at room temperature using atom-atom distance restraints measured for HEWL in TFE/water solution satisfies the experimental data and has the lowest protein energy. In this ensemble residues 50–58, which are part of the β-sheet in native HEWL, adopt fluctuating α-helical secondary structure.

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Acknowledgments

We thank Matthias Buck for giving us the list of NOEs for lysozyme in TFE used in the structure calculations reported in his D. Phil. thesis and for helpful advise and discussion. This work was financially supported by the National Center of Competence in Research (NCCR) in Structural Biology and by Grant number 200020-137827 of the Swiss National Science Foundation, and by Grant number 228076 of the European Research Council, which is gratefully acknowledged.

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Authors and Affiliations

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

    Andreas P. Eichenberger & Wilfred F. van Gunsteren

  2. Department of Chemistry, Inorganic Chemistry Laboratory, University of Oxford, Oxford, OX1 3QR, UK

    Lorna J. Smith

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  1. Andreas P. Eichenberger
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  2. Wilfred F. van Gunsteren
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Correspondence to Wilfred F. van Gunsteren.

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Eichenberger, A.P., van Gunsteren, W.F. & Smith, L.J. Structure of hen egg-white lysozyme solvated in TFE/water: a molecular dynamics simulation study based on NMR data. J Biomol NMR 55, 339–353 (2013). https://doi.org/10.1007/s10858-013-9717-y

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