Volume 6 Supplement 1

9th German Conference on Chemoinformatics, GCC2013

Open Access

De novo design of selective compounds: a fragment-based pipeline applied to the β2 adrenergic receptor

Journal of Cheminformatics20146(Suppl 1):P25

DOI: 10.1186/1758-2946-6-S1-P25

Published: 11 March 2014

GPCRs play a key role in transmembrane signaling and are involved in many physiological processes, such as regulation of behavior, heart rate and the immune system. Therefore they are very important targets for pharmaceutical agents. Our project focuses on the β2 Adrenergic Receptor [1, 2] (β2AR). The β2AR is mainly involved in vasodilation and bronchodilation in the human body. The recently solved structures of the β2AR open up new possibilities in the design of novel specific ligands using structure-based approaches. Here, we describe a pipeline to grow an unspecific fragment-sized scaffold for the β2AR. The protocol uses focused docking of fragments in two different zones identified within the binding site. The top ranked fragments are then computationally added to the core scaffold, filtered, minimized, evaluated by flexible ligand docking and inspected for later synthesis. Our initial results show that promising ligands can be identified by adding discriminating fragments to a core scaffold and that the generated compounds provide a reasonable synthetic accessibility.

Authors’ Affiliations

(1)
Kolblab, Institute of Pharmaceutical Chemistry, Philipps-University Marburg

References

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Copyright

© Chevillard and Kolb; licensee Chemistry Central Ltd. 2014

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. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.