LigandScout:  3-D Pharmacophores Derived from Protein-Bound Ligands and Their Use as Virtual Screening Filters

Gerhard Wolber*† and Thierry Langer‡
Inte:Ligand GmbH, Mariahilferstrasse 74B/11, A-1070 Vienna, Austria, and Computer Aided Molecular Design Group, Department of Pharmaceutical Chemistry, Institute of Pharmacy, University of Innsbruck, Innrain 52, A-6020 Innsbruck, Austria
J. Chem. Inf. Model., 2005, 45 (1), pp 160–169
DOI: 10.1021/ci049885e
Publication Date (Web): November 24, 2004
Copyright © 2005 American Chemical Society
*

 Corresponding author phone:  +43 6991 507 5000; fax:  +43 1 8174955 1371; e-mail:  wolber@inteligand.com.

,
†

 Inte:Ligand GmbH.

,
‡

 University of Innsbruck.

Abstract

From the historically grown archive of protein−ligand complexes in the Protein Data Bank small organic ligands are extracted and interpreted in terms of their chemical characteristics and features. Subsequently, pharmacophores representing ligand−receptor interaction are derived from each of these small molecules and its surrounding amino acids. Based on a defined set of only six types of chemical features and volume constraints, three-dimensional pharmacophore models are constructed, which are sufficiently selective to identify the described binding mode and are thus a useful tool for in-silico screening of large compound databases. The algorithms for ligand extraction and interpretation as well as the pharmacophore creation technique from the automatically interpreted data are presented and applied to a rhinovirus capsid complex as application example.

View: Full Text HTML | Hi-Res PDF

Tools

History

  • Published In Issue January 24, 2005
  • Received April 3, 2004

Recommend & Share

Related Content

Other ACS content by these authors: