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Bioinformatics Advance Access published online on February 8, 2005
Bioinformatics, doi:10.1093/bioinformatics/bti315
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© The Author (2005). Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oupjournals.org
Received December 22, 2004
Revised January 31, 2005
Accepted February 7, 2005

Article

Q-SiteFinder: an energy-based method for the prediction of protein-ligand binding sites

Alasdair T. R. Laurie 1 and Richard M. Jackson 1*

1 School of Biochemistry & Molecular Biology, University of Leeds, Leeds, LS2 9JT

* To whom correspondence should be addressed.
Richard M. Jackson, E-mail: r.m.jackson{at}leeds.ac.uk


  Abstract

Motivation: Identifying the location of ligand binding sites on a protein is of fundamental importance for a range of applications including molecular docking, de novo drug design and structural identification and comparison of functional sites. Here, we describe a new method of ligand binding site prediction called Q-SiteFinder. It uses the interaction energy between the protein and a simple van der Waals probe to locate energetically favourable binding sites. Energetically favourable probe sites are clustered according to their spatial proximity and clusters are then ranked according to the sum of interaction energies for sites within each cluster.

Results: There is at least one successful prediction in the top three predicted sites in 90% of proteins tested when using Q-SiteFinder. This success rate is higher than that of a commonly used pocket detection method (Pocket-Finder) which uses geometric criteria. Additionally, Q-SiteFinder is twice as effective as Pocket-Finder in generating predicted sites that map accurately onto ligand coordinates. It also generates predicted sites with the lowest average volumes of the algorithms examined in this study. Unlike pocket detection, the volumes of the predicted sites appear to show relatively low dependence on protein volume and are similar in volume to the ligands they contain. Restricting the size of the pocket is important for reducing the search space required for docking and de novo drug design or site comparison. The method can be applied in structural genomics studies where protein binding sites remain uncharacterised since the 86% success rate for unbound proteins appears to be only slightly lower than that of ligand-bound proteins.

Availability: Both Q-SiteFinder and Pocket-Finder have been made available online at http://www.bioinformatics.leeds.ac.uk/qsitefinder and http://www.bioinformatics.leeds.ac.uk/pocketfinder.


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