To probe the selective mechanism of agonists binding to three opioid receptor 
subtypes, ligand-based and receptor-based methods were implemented together and 
subtype characteristics of opioid agonists were clearly described. Three 
pharmacophore models of opioid agonists were generated by the Catalyst/HypoGen 
program. The best pharmacophore models for μ, δ and κ agonists contained four, 
five and five features, respectively. Meanwhile, the three-dimensional 
structures of three receptor subtypes were modeled on the basis of the crystal 
structure of β2-adrenergic receptor, and molecular docking was conducted 
further. According to these pharmacophore models and docking results, the 
similarities and differences among agonists of three subtypes were identified. μ 
or δ agonists, for example, could form one hydrogen bond separately with Tyr129 
and Tyr150 at TMIII, whereas κ ones formed a π-π interaction in that place. 
These findings may be crucial for the development of novel selective analgesic 
drugs.