Positively Charged Nitrogen is Not Indispensable Requirement for Binding of Nitrogenous κ-Opioid Agonists: Insights from Docking Studies
Indrani Bera and Nanda Ghoshal
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.
Keywords: Agonist, Docking, Kappa opioid receptor, Non-peptidic, Opioids, Protonated nitrogen.
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