A Pseudo-Ligand Approach to Virtual Screening

Title: A Pseudo-Ligand Approach to Virtual Screening

Volume: 9 Issue: 5

Author(s): Andreas Schuller, Uli Fechner, Steffen Renner, Lutz Franke, Lutz Weber and Gisbert Schneider

Affiliation:

Keywords: Chemoinformatics, pharmacophore, similarity, drug design, combinatorial library, binding pocket

Abstract: A virtual screening method is presented that is grounded on a receptor-derived pharmacophore model termed "virtual ligand" or "pseudo-ligand". The model represents an idealized constellation of potential ligand sites that interact with residues of the binding pocket. For rapid virtual screening of compound libraries the potential pharmacophore points of the virtual ligand are encoded as an alignment-free correlation vector, avoiding spatial alignment of pharmacophore features between the pharmacophore query (i.e., the virtual ligand) and the candidate molecule. The method was successfully applied to retrieving factor Xa inhibitors from a Ugi three-component combinatorial library, and yielded high enrichment of actives in a retrospective search for cyclooxygenase-2 (COX-2) inhibitors. The approach provides a concept for "de-orphanizing" potential drug targets and identifying ligands for hitherto unexplored or allosteric binding pockets.

Cite this article as:

Schuller Andreas, Fechner Uli, Renner Steffen, Franke Lutz, Weber Lutz and Schneider Gisbert, A Pseudo-Ligand Approach to Virtual Screening, Combinatorial Chemistry & High Throughput Screening 2006; 9 (5) . https://dx.doi.org/10.2174/138620706777452375