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Issue 1, 2013
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A monomeric form of iNOS can rationalise observed SAR for inhibitors of dimerisation: quantum mechanics and docking compared

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Abstract

Two series of compounds that inhibit dimerisation of iNOS have been reported in the literature and studied crystallographically. We have applied a range of docking techniques to these compounds and shown that the geometry of the complexes can be reproduced well but that even within a series of related compounds the docking scores do not rank compounds well. Quantum mechanical studies using a model system for the protein and a range of density functionals are able to reproduce the geometry of the complexes and the corresponding affinities. The combination of docking to generate geometries and quantum mechanical calculations to predict complexation energies is a powerful one for rationalising observed changes and designing improved compounds.

Graphical abstract: A monomeric form of iNOS can rationalise observed SAR for inhibitors of dimerisation: quantum mechanics and docking compared

  • This article is part of the themed collection: New Talent
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Publication details

The article was received on 15 Jun 2012, accepted on 06 Sep 2012 and first published on 14 Sep 2012


Article type: Concise Article
DOI: 10.1039/C2MD20159C
Citation: Med. Chem. Commun., 2013,4, 180-186
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    A monomeric form of iNOS can rationalise observed SAR for inhibitors of dimerisation: quantum mechanics and docking compared

    A. G. Leach, L. Olsson and D. J. Warner, Med. Chem. Commun., 2013, 4, 180
    DOI: 10.1039/C2MD20159C

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