Volume 5 Supplement 1

8th German Conference on Chemoinformatics: 26 CIC-Workshop

Open Access

Application of Structural Interaction Fingerpints (SIFts) into post-docking analysis - insight into activity and selectivity

  • Jagna Witek1Email author,
  • Krzysztof Rataj1,
  • Stefan Mordalski1,
  • Sabina Smusz1,
  • Tomasz Kosciolek1 and
  • Andrzej J Bojarski1
Journal of Cheminformatics20135(Suppl 1):P28

DOI: 10.1186/1758-2946-5-S1-P28

Published: 22 March 2013

Cheminformatic methods, such as Virtual Screening, constitute a vital part of modern drug design process. This technique enables not only viable prediction of physicochemical properties of the molecules, but also effective database mining, being particularly useful tool in search for ligands of desired activity. Successful performance in case of single target drugs, implies a potential to extend its capabilities to compounds bearing desired activity towards multiple receptors.

In this research, we present application of Structural Interaction Fingerprints (SIFts) [1] combined with Machine Learning (ML) as a method to select single- and multi-target ligands from the docking results. A handful of protein kinases pairs was designated as targets. Collection of pseudo selective compounds, with various activity profiles, was acquired from ChEMBL database. Furthermore, for each target a set of ligands of various activity was aggregated. Decoy structures were random ligands from ZINC database. The compounds were docked into respective proteins, and SIFts were calculated for each protein-ligand complex. Training sets used in ML experiments consisted of cluster centroids of active and inactive ligands, whereas test sets were composed of remaining compounds, that returned docking poses.

The key aim of this study is to develop a viable method to filter the docking results, so that the compounds meeting desired activity profile are selected.

Declarations

Acknowledgements

This study was supported by project UDA-POIG.01.03.01-12-100/08-00 co-financed by European Union from the European Fund of Regional Development (EFRD); http://www.prokog.pl.

Authors’ Affiliations

(1)
Department of Medicinal Chemistry, Institute of Pharmacology Polish Academy of Sciences

References

  1. Deng Z, Chuaqui C: Structural Interaction Fingerprint (SIFt): A Novel Method for Analyzing Three-Dimensional Protein-Ligand Binding Interactions. J Med Chem. 2004, 47: 337-344. 10.1021/jm030331x.View ArticleGoogle Scholar

Copyright

© Witek et al.; licensee BioMed Central Ltd. 2013

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.