Docking studies on a refined human β₂ adrenoceptor model yield theoretical affinity values in function with experimental values for R-ligands, but not for S-antagonists

G-protein coupled receptors (GPCR) belong to the largest group of membrane proteins involved in signal transduction. These receptors are implicated in diverse physiological and pathological events. The human β₂ adrenergic receptor (hβ₂AR) is one of the few GPCRs whose 3-D structures are available on the Protein Data Bank. Because there is great interest by drug developers for hβ₂AR as a target, it is necessary to study its ligand-recognition process at the atomic level. The hβ₂AR can recognize both R/S enantiomeric ligands, R-agonists result in a greater activation than do S-agonists (eutomers and distomers for activation, respectively), according to experimental results. In this work is reported the ligand recognition on a refined hβ₂AR-structure of a set of well-known R/S-ligands by means of docking studies. Data obtained in silico were analyzed and compared with those reported in vitro. The theoretical affinity values were reproduced for agonists, but not for antagonist (or inverse agonists). However, theoretical data for R-antagonists are in function to experimental data. The theoretical results confirm the role of amino acids previously reported by mutagenesis studies due to their important roles in drug affinity and stereoselectivity.