LigandScout: 3-D pharmacophores derived from protein-bound ligands and their use as virtual screening filters

J Chem Inf Model. 2005 Jan-Feb;45(1):160-9. doi: 10.1021/ci049885e.

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.

MeSH terms

  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Antiviral Agents / chemistry
  • Antiviral Agents / pharmacology
  • Drug Design*
  • Fusion Proteins, bcr-abl
  • Hydrogen Bonding
  • Ligands*
  • Models, Chemical
  • Models, Molecular
  • Molecular Conformation
  • Protein Binding
  • Protein-Tyrosine Kinases / antagonists & inhibitors
  • Rhinovirus / drug effects
  • Software

Substances

  • Antineoplastic Agents
  • Antiviral Agents
  • Ligands
  • Protein-Tyrosine Kinases
  • Fusion Proteins, bcr-abl