Affordable Access

Publisher Website

Combining docking with pharmacophore filtering for improved virtual screening

Authors
Journal
Journal of Cheminformatics
1758-2946
Publisher
Springer (Biomed Central Ltd.)
Publication Date
Volume
1
Issue
1
Identifiers
DOI: 10.1186/1758-2946-1-6
Keywords
  • Research Article
Disciplines
  • Biology
  • Chemistry
  • Pharmacology

Abstract

Background Virtual screening is used to distinguish potential leads from inactive compounds in a database of chemical samples. One method for accomplishing this is by docking compounds into the structure of a receptor binding site in order to rank-order compounds by the quality of the interactions they form with the receptor. It is generally established that docking can be reasonably successful at generating good poses of a ligand in an active site. However, the scoring functions that are used with docking are typically not successful at correctly ranking ligands according to binding affinity or even distinguishing correct poses of a given ligand from incorrect ones. Results We have developed a simple method for reducing the number of false positives in a virtual screen, meaning ligands which are scored highly by the docking program but do not bind well in reality. This method uses a docking program for pose generation without regard to scoring, followed by filtering with receptor-based pharmacophore searches. We applied it to three test-case targets: neuraminidase A, cyclin-dependent kinase 2, and the C1 domain of protein kinase C. Conclusion The pharmacophore filtering method can perform better than more traditional docking + scoring methods, and allows the advantages of both docking-based and pharmacophore-based approaches to virtual screening to be fully realized.

There are no comments yet on this publication. Be the first to share your thoughts.

Statistics

Seen <100 times
0 Comments

More articles like this

Development and evaluation of an integrated virtua...

on Journal of chemical informatio... Oct 28, 2013

Pharmacophore-based virtual screening and docking...

on SAR and QSAR in environmental... July 2010

Virtual screening of cathepsin k inhibitors using...

on Chemical Biology & Drug Design July 2008
More articles like this..