Journal of Computer-Aided Molecular Design

, Volume 20, Issue 10, pp 673–684

Molecular dynamics simulation of the human adenosine A3 receptor: agonist induced conformational changes of Trp243

Original Paper

DOI: 10.1007/s10822-006-9088-5

Cite this article as:
Hallmen, C. & Wiese, M. J Comput Aided Mol Des (2006) 20: 673. doi:10.1007/s10822-006-9088-5


The adenosine A3 receptor together with rhodopsin belongs to Class A of the G-protein coupled receptors. As the crystal structure of bovine rhodopsin represents the dark (inactive) state of the receptor, the details of GPCR activation are still unknown. In this molecular dynamics study we investigate how the homology model of the human adenosine A3 receptor responds to ligand exposure. To this end we placed the homology model in a POPC membrane model. After equilibrating for 13 ns an agonist (Cl-IB-MECA) and an inverse agonist (PSB-10) were placed inside the putative binding pocket. In the following 10 ns molecular dynamics simulation we observed a different behaviour of the side-chain torsions of Trp2436.48, depending on the presence or absence of the agonist or inverse agonist. This conformational change of Trp243 correlates with the assumed influence of ligands on receptor activation. Other predicted conformational changes of the receptor could not be observed yet. So Trp243 may represent the first switch in receptor activation.


Adenosine A3 receptor GPCR Molecular dynamics Phospholipid bilayer Receptor activation 

Copyright information

© Springer Science+Business Media, LLC 2006

Authors and Affiliations

  1. 1.Pharmaceutical InstituteUniversity of BonnBonnGermany