Volume 4 Supplement 1

7th German Conference on Chemoinformatics: 25 CIC-Workshop

Open Access

Synergistic approach of structure-based and ligand-based drug design for the development of selective cannabinod receptor ligands

Journal of Cheminformatics20124(Suppl 1):P11

https://doi.org/10.1186/1758-2946-4-S1-P11

Published: 1 May 2012

Cannabinoid receptors (CB) are G-protein coupled receptors involved in many physiological processes, like learning, appetite, nociception and others. Two subtypes (termed CB1 and CB2) are involved in slightly different processes [1]. Thus, it is important to gain more insight into the the cannabinoid receptor system and the potential effects of cannabinoid therapeutics.

By combining [2] 3D-QSAR, pharmacophore modeling, comparative modeling and molecular docking we could identify features responsible for receptor subtype specificity.

Various pharmacophore models were derived from in-house libraries and data available in the literature. 3D structures of both receptor subtypes were created employing comparative modeling methods. The models were subjected to molecular simulations in solvated lipid bilayers to sample different receptor conformations. The models were used for molecular docking studies with small compound libraries. Employing the data obtained in the pharmacophore/3D-QSAR studies as additional constraints delivered valuable information on affinity and selectivity of the compounds towards CB1 and CB2. The results from this synergistic modeling approach could improve our understanding of the protein–ligand interactions involved.

Declarations

Acknowledgements

This synergistic approach has been implemented into the MOE modeling package (MOE: Chemical Computing Group Inc. Montreal. H3A 2R7 Canada. http://www.chemcomp.com).

Authors’ Affiliations

(1)
Institute of Radiopharmacy, Helmholtz-Zentrum Dresden-Rossendorf, Research Site Leipzig

References

  1. Pertwee RG: Ligands that target cannabinoid receptors in the brain: from THC to anandamide and beyond. Addict Biol. 2008, 13: 147-159. 10.1111/j.1369-1600.2008.00108.x.View ArticleGoogle Scholar

Copyright

© Günther and Brust; licensee BioMed Central Ltd. 2012

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.