Journal of Computer-Aided Molecular Design

, Volume 18, Issue 5, pp 361–374 | Cite as

GRIND-derived pharmacophore model for a series of α-tropanyl derivative ligands of the sigma-2 receptor*

  • Paola Cratteri
  • M. Novella Romanelli
  • Gabriele Cruciani
  • Claudia Bonaccini
  • Fabrizio Melani
Article

Abstract

A pharmacophore model for the sigma-2 receptor was derived using GRIND (GRid INdependent Descriptors) descriptors arising from a 3D-level procedure whose main prerogative is that it does not require ligand alignment. PLS models for sigma-2 affinity (sigma-2 model: r2=0.83, q2=0.63) and sigma-1/sigma-2 selectivity (r2=0.72, q2=0.46) were derived using a series of α-tropanyl derivatives. The models provide pictures of the virtual receptor site (VRS) significant enough to attain a qualitative pharmacophoric representation of the sigma receptor. They give the internal geometrical relationships within two hydrophobic areas (hydrophobic-1 and -2) and a H-bond donor receptor region with which ligands establish non-covalent bonds.

alignment free 3D descriptors GRIND descriptors pharmacophore model sigma ligands sigma receptor 

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Copyright information

© Kluwer Academic Publishers 2004

Authors and Affiliations

  • Paola Cratteri
    • 1
    • 1
  • M. Novella Romanelli
    • 1
  • Gabriele Cruciani
    • 2
  • Claudia Bonaccini
    • 1
  • Fabrizio Melani
    • 1
  1. 1.Department of Pharmaceutical SciencesUniversity of Florence, via U. Schiff 6FirenzeItaly
  2. 2.Laboratory for ChemometricsUniversity of Perugia, Via Elce di Sotto 8PerugiaItaly

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