Affiliation: Structural Biology & Bioinformatics Division, CSIR-Indian Institute of Chemical Biology, 4 Raja S. C. Mullick Road, Kolkata – 700 032, India.
Induced fit docking approach was utilized to decipher the binding mode of the recently reported dibenz[b,f]1,5- oxazocine derivative having activity towards κ -Opioid receptor. The result of docking to newly resolved crystallographic structure of κ -Opioid receptor established the important interactions as two hydrogen bonds, a π-π interaction, and two hydrophobic interactions. Based on the study it is inferred that protonated nitrogen is not always essential for binding of non-peptidic nitrogen containing opioids to κ -Opioid receptor. Also, docking was performed using well-known kappa agonist pentazocine to prove different binding requirements of the dibenzo compound. A pharmacophoric model has been developed based on the previously known nitrogen containing κ -Opioid receptor agonists and the new dibenzo compound to determine the minimal 3D features, required for κ -Opioid agonist activity. To our knowledge, this is the first report of a binding mode analysis study for non-protonated nitrogen containing κ-Opioid receptor agonist.