Investigation of D₁ receptor-agonist interactions and D₁/D₂ agonist selectivity using a combination of pharmacophore and receptor homology modeling.

ABSTRACT: The aim of this study was to use a combined structure and pharmacophore modeling approach to extract information regarding dopamine D₁ receptor agonism and D₁/D₂ agonist selectivity. A 3D structure model of the D₁ receptor in its agonist-bound state was constructed with a full D₁ agonist present in the binding site. Two different binding modes were identified using (+)-doxanthrine or SKF89626 in the modeling procedure. The 3D model was further compared with a selective D₁ agonist pharmacophore model. The pharmacophore feature arrangement was found to be in good agreement with the binding site composition of the receptor model, but the excluded volumes did not fully reflect the shape of the agonist binding pocket. A new receptor-based pharmacophore model was developed with forbidden volumes

SUBMITTER: Malo M 

PROVIDER: S-EPMC3382191 | biostudies-literature | 2012 Mar

REPOSITORIES: biostudies-literature