LigandScout: 3-D pharmacophores derived from protein-bound ligands and their use as virtual screening filters.
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.
Wolber
Gerhard
G
Inte:Ligand GmbH, Mariahilferstrasse 74B/11, A-1070 Vienna, Austria. wolber@inteligand.com
Langer
Thierry
T
D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D000998:Antiviral Agents / Q000737:chemistry / Q000494:pharmacology; D015195:Drug Design; D016044:Fusion Proteins, bcr-abl; D006860:Hydrogen Bonding; D008024:Ligands; D008956:Models, Chemical; D008958:Models, Molecular; D008968:Molecular Conformation; D011485:Protein Binding; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D012229:Rhinovirus / Q000187:drug effects; D012984:Software
D000970:Antineoplastic Agents; D000998:Antiviral Agents; D008024:Ligands; D011505:Protein-Tyrosine Kinases; D016044:Fusion Proteins, bcr-abl