Journal of Computer-Aided Molecular Design

, Volume 14, Issue 4, pp 341–353 | Cite as

3D-QSAR methods on the basis of ligand–receptor complexes. Application of COMBINE and GRID/GOLPE methodologies to a series of CYP1A2 ligands

  • Juan José Lozano
  • Manuel Pastor
  • Gabriele Cruciani
  • Katrin Gaedt
  • Nuria B. Centeno
  • Federico Gago
  • Ferran Sanz


Many heterocyclic amines (HCA) present in cooked food exert a genotoxic activity when they are metabolised (N-oxidated) by the human cytochrome P450 1A2 (CYP1A2h). In order to rationalize the observed differences in activity of this enzyme on a series of 12 HCA, 3D-QSAR methods were applied on the basis of models of HCA–CYP1A2h complexes. The CYP1A2h enzyme model has been previously reported and was built by homology modeling based on cytochrome P450 BM3. The complexes were automatically generated applying the AUTODOCK software and refined using AMBER. A COMBINE analysis on the complexes identified the most important enzyme–ligand interactions that account for the differences in activity within the series. A GRID/GOLPE analysis was then performed on just the ligands, in the conformations and orientations found in the modeled complexes. The results from both methods were concordant and confirmed the advantages of incorporating structural information from series of ligand–receptor complexes into 3D-QSAR methodologies.

AUTODOCK COMBINE cooked food heterocyclic amines cytochrome P450 1A2 docking simulation GRID/GOLPE 3D-QSAR 


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Copyright information

© Kluwer Academic Publishers 2000

Authors and Affiliations

  • Juan José Lozano
    • 1
  • Manuel Pastor
    • 2
  • Gabriele Cruciani
    • 2
  • Katrin Gaedt
    • 1
  • Nuria B. Centeno
    • 1
  • Federico Gago
    • 3
  • Ferran Sanz
    • 1
  1. 1.Research Group on Medical Informatics, IMIMBarcelonaSpain
  2. 2.Laboratory on Chemometrics, Department of ChemistryUniversità di PerugiaPerugiaItaly
  3. 3.Department of PharmacologyUniversidad de AlcaláMadridSpain

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