Computational prediction of monosaccharide binding free energies to lectins with linear interaction energy models

Authors

  • Sushil Kumar Mishra,

    1. Central European Institute of Technology, Masaryk University, Kamenice 5, 625 00 Brno, Czech Republic
    2. National Centre for Biomolecular Research, Faculty of Science, Masaryk University, Kotlářská 2, 611 37 Brno, Czech Republic
    Search for more papers by this author
  • Johan Sund,

    1. Department of Cell and Molecular Biology, Uppsala University, Biomedical Center, Box 596, SE-571 24 Uppsala, Sweden
    Search for more papers by this author
  • Johan Åqvist,

    1. Department of Cell and Molecular Biology, Uppsala University, Biomedical Center, Box 596, SE-571 24 Uppsala, Sweden
    Search for more papers by this author
  • Jaroslav Koča

    Corresponding author
    1. Central European Institute of Technology, Masaryk University, Kamenice 5, 625 00 Brno, Czech Republic
    2. National Centre for Biomolecular Research, Faculty of Science, Masaryk University, Kotlářská 2, 611 37 Brno, Czech Republic
    • Central European Institute of Technology, Masaryk University, Kamenice 5, 625 00 Brno, Czech Republic
    Search for more papers by this author

Abstract

The linear interaction energy (LIE) method to compute binding free energies is applied to lectin-monosaccharide complexes. Here, we calculate the binding free energies of monosaccharides to the Ralstonia solanacearum lectin (RSL) and the Pseudomonas aeruginosa lectin-II (PA-IIL). The standard LIE model performs very well for RSL, whereas the PA-IIL system, where ligand binding involves two calcium ions, presents a major challenge. To overcome this, we explore a new variant of the LIE model, where ligand–metal ion interactions are scaled separately. This model also predicts the saccharide binding preference of PA-IIL on mutation of the receptor, which may be useful for protein engineering of lectins. © 2012 Wiley Periodicals, Inc.

Ancillary