Volume 2 Supplement 1

3rd German Conference on Chemoinformatics: 21. CIC-Workshop

Open Access

Adrenoceptors: ligand-activated molecular dynamics

  • B Matijssen1,
  • G Watson1 and
  • I Rozas1
Chemistry Central Journal20082(Suppl 1):P36


Published: 26 March 2008

Adrenoceptors [1] belong to class A of the superfamily of G protein coupled receptors (GPCRs) that transduce signals across the cell membrane, thus initiating a variety of intracellular biochemical events. The adrenoceptors subtypes (α1A, α1B and α1D) are of particular therapeutic interest due to their important role in benign prostatic hyperplasia, a medical condition associated with old age.

Our knowledge of the structure of GPCRs and particularly in adrenoceptors is limited. The only available GPCR crystal structure is that of bovine rhodopsin, which has been characterised with different resolutions, being the most refined 2.2 Å (pdb: 1U19fig 1). Utilising the structural data from this structure we were able to produce homology models of the different subtypes α1A- α1B- and α1D-adrenoceptor.

An optimisation and protonation state determination of a selection of ligands has been performed using B3LYP with a 6-31G* basis set. This allowed us to determine the nitrogen of the ligand which is most likely to be protonated. This plays a significant part in ligand-protein interaction.

Molecular dynamics (using the AMBER 9.0 package) has been used to simulate the structural movements of the adrenoceptors due to the influence of the ligands [2]. This results in structures that can possibly represent the active form of the receptor.

Authors’ Affiliations

University of Dublin, Trinity College Dublin, School of Chemistry, College Green, Dublin 2, Ireland


  1. Calzada B, Arinano A: Pharm Res. 2001, 44: 195-208. 10.1006/phrs.2001.0857.View ArticleGoogle Scholar
  2. Kinsella G, Rozas I, Watson G: J Med Chem. 2006, 49: 501-510. 10.1021/jm0503751.View ArticleGoogle Scholar


© Matijssen et al. 2008