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Prediction of electrostatic effects of engineering of protein charges

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Abstract

Accurate prediction of electrostatic effects on catalytic activity is an essential component of protein design1–4. Site-directed mutagenesis of charged groups in subtilisin of Bacillus amyloliquefaciens has provided experimental measurements of electrostatic interactions which may be used to test such theoretical methods. The pKa of the histidine of the active site has been perturbed by +0.08 to –1.0 units by modifying one or two residues5–7. Electrostatic effects in proteins can be modelled by the algorithm of Warwicker and Watson, which uses classical electrostatics and considers both the charge position and the shape of the molecule8–10. Here we report that the algorithm can model several pKa shifts in subtilisin to fair accuracy.

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References

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Authors and Affiliations

  1. Department of Crystallography, Birkbeck College, Malet Street, London, WC1E 7HX, UK

    Michael J. E. Sternberg & Fiona R. F. Hayes

  2. Department of Chemistry, Imperial College of Science and Technology, London, SW7 2AY, UK

    Alan J. Russell, Paul G. Thomas & Alan R. Fersht

Authors
  1. Michael J. E. Sternberg
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  2. Fiona R. F. Hayes
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  3. Alan J. Russell
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  4. Paul G. Thomas
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  5. Alan R. Fersht
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Sternberg, M., Hayes, F., Russell, A. et al. Prediction of electrostatic effects of engineering of protein charges. Nature 330, 86–88 (1987). https://doi.org/10.1038/330086a0

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  • DOI: https://doi.org/10.1038/330086a0

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