Nonuniform charge scaling (NUCS): A practical approximation of solvent electrostatic screening in proteins

Authors

  • Sonja M. Schwarzl,

    1. Computational Biochemistry, Interdisciplinary Center for Scientific Computing (IWR), University of Heidelberg, Im Neuenheimer Feld 368, D-69120 Heidelberg, Germany
    2. Computational Molecular Biophysics, Interdisciplinary Center for Scientific Computing (IWR), University of Heidelberg, Im Neuenheimer Feld 368, D-69120 Heidelberg, Germany
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  • Danzhi Huang,

    1. Computational Biochemistry, Interdisciplinary Center for Scientific Computing (IWR), University of Heidelberg, Im Neuenheimer Feld 368, D-69120 Heidelberg, Germany
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  • Jeremy C. Smith,

    1. Computational Molecular Biophysics, Interdisciplinary Center for Scientific Computing (IWR), University of Heidelberg, Im Neuenheimer Feld 368, D-69120 Heidelberg, Germany
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  • Stefan Fischer

    Corresponding author
    1. Computational Biochemistry, Interdisciplinary Center for Scientific Computing (IWR), University of Heidelberg, Im Neuenheimer Feld 368, D-69120 Heidelberg, Germany
    • Computational Biochemistry, Interdisciplinary Center for Scientific Computing (IWR), University of Heidelberg, Im Neuenheimer Feld 368, D-69120 Heidelberg, Germany
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Abstract

In molecular mechanics calculations, electrostatic interactions between chemical groups are usually represented by a Coulomb potential between the partial atomic charges of the groups. In aqueous solution these interactions are modified by the polarizable solvent. Although the electrostatic effects of the polarized solvent on the protein are well described by the Poisson–Boltzmann equation, its numerical solution is computationally expensive for large molecules such as proteins. The procedure of nonuniform charge scaling (NUCS) is a pragmatic approach to implicit solvation that approximates the solvent screening effect by individually scaling the partial charges on the explicit atoms of the macromolecule so as to reproduce electrostatic interaction energies obtained from an initial Poisson–Boltzmann analysis. Once the screening factors have been determined for a protein the scaled charges can be easily used in any molecular mechanics program that implements a Coulomb term. The approach is particularly suitable for minimization-based simulations, such as normal mode analysis, certain conformational reaction path or ligand binding techniques for which bulk solvent cannot be included explicitly, and for combined quantum mechanical/molecular mechanical calculations when the interface to more elaborate continuum solvent models is lacking. The method is illustrated using reaction path calculations of the Tyr35 ring flip in the bovine pancreatic trypsin inhibitor. © 2005 Wiley Periodicals, Inc. J Comput Chem 26: 1359–1371, 2005

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