Predicted 3D structure for the human beta 2 adrenergic receptor and its binding site for agonists and antagonists.

ABSTRACT: We report the 3D structure of human beta2 adrenergic receptor (AR) predicted by using the MembStruk first principles method. To validate this structure, we use the HierDock first principles method to predict the ligand-binding sites for epinephrine and norepinephrine and for eight other ligands, including agonists and antagonists to beta 2 AR and ligands not observed to bind to beta 2 AR. The binding sites agree well with available mutagenesis data, and the calculated relative binding energies correlate reasonably with measured binding affinities. In addition, we find characteristic differences in the predicted binding sites of known agonists and antagonists that allow us to infer the likely activity of other ligands. The predicted ligand-binding properties validate the methods used to pre

SUBMITTER: Freddolino PL 

PROVIDER: S-EPMC365690 | biostudies-literature | 2004 Mar

REPOSITORIES: biostudies-literature