Study of Molecular Docking of Mu Opioid Receptor Agonist - Fentanyl and its Analogs Based on Docking

2013 ◽  
Vol 655-657 ◽  
pp. 1931-1934 ◽  
Author(s):  
Ming Liu ◽  
Lei Wang ◽  
Xiao Li Liu ◽  
Wen Xiang Hu
Keyword(s):  
Molecular Docking ◽  
Opioid Receptor ◽  
3D Structure ◽  
Interaction Mechanism ◽  
Mu Opioid Receptor ◽  
Mu Opioid ◽  
Opioid Receptor Agonist ◽  
Fentanyl Analogs ◽  
Fully Automatic ◽  
Surflex Docking

The interaction mechanism of a series of fentanyl analogs are examined using molecular docking to the mu-opioid receptor based on Surflex-Docking. Fully automatic flexible molecular docking (Surflex-Docking) was performed by using the possible active conformations of 70 fentanyl analogs and optimized 3D structure of mu-opioid receptor. The site mainly consist of residues ILE 109, ASP 112, TYR113, MET116, HIS262, TYR291. All these residues take part in interaction between fentanyl and mu-opioid receptor. Meanwhile, the results provide new insight to design of experiments aimed at understanding the structure.

scholarly journals A bifunctional nociceptin and mu opioid receptor agonist is analgesic without opioid side effects in nonhuman primates

2018 ◽  
Vol 10 (456) ◽  
pp. eaar3483 ◽  
Author(s):  
Huiping Ding ◽  
Norikazu Kiguchi ◽  
Dennis Yasuda ◽  
Pankaj R. Daga ◽  
Willma E. Polgar ◽  
...  
Keyword(s):  
Side Effects ◽  
Opioid Receptor ◽  
Receptor Agonist ◽  
Nonhuman Primates ◽  
Mu Opioid Receptor ◽  
Mu Opioid ◽  
Opioid Receptor Agonist

Discovery of a novel bicyclic compound, DS54360155, as an orally potent analgesic without mu-opioid receptor agonist activity

2019 ◽  
Vol 29 (23) ◽  
pp. 126748
Author(s):  
Tsuyoshi Arita ◽  
Masayoshi Asano ◽  
Kazufumi Kubota ◽  
Yuki Domon ◽  
Nobuo Machinaga ◽  
...  
Keyword(s):  
Opioid Receptor ◽  
Receptor Agonist ◽  
Mu Opioid Receptor ◽  
Bicyclic Compound ◽  
Agonist Activity ◽  
Mu Opioid ◽  
Opioid Receptor Agonist

scholarly journals Peripherally acting mu-opioid receptor agonist attenuates neuropathic pain in rats after L5 spinal nerve injury

Pain ◽  
2008 ◽  
Vol 138 (2) ◽  
pp. 318-329 ◽  
Author(s):  
Yun Guan ◽  
Lisa M. Johanek ◽  
Timothy V. Hartke ◽  
Beom Shim ◽  
Yuan-Xiang Tao ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Nerve Injury ◽  
Opioid Receptor ◽  
Receptor Agonist ◽  
Mu Opioid Receptor ◽  
Spinal Nerve ◽  
Mu Opioid ◽  
Opioid Receptor Agonist

scholarly journals Topical treatment with a mu opioid receptor agonist alleviates corneal allodynia and corneal nerve sensitization in mice

2020 ◽  
Vol 132 ◽  
pp. 110794
Author(s):  
Fanny Joubert ◽  
Adrian Guerrero-Moreno ◽  
Darine Fakih ◽  
Elodie Reboussin ◽  
Claire Gaveriaux-Ruff ◽  
...  
Keyword(s):  
Opioid Receptor ◽  
Topical Treatment ◽  
Receptor Agonist ◽  
Mu Opioid Receptor ◽  
Mu Opioid ◽  
Opioid Receptor Agonist ◽  
Corneal Nerve

scholarly journals Mechanistic Understanding of Peptide Analogues, DALDA, [Dmt1]DALDA, and KGOP01, Binding to the Mu Opioid Receptor

Molecules ◽  
2020 ◽  
Vol 25 (9) ◽  
pp. 2087 ◽  
Author(s):  
Maria Dumitrascuta ◽  
Marcel Bermudez ◽  
Steven Ballet ◽  
Gerhard Wolber ◽  
Mariana Spetea
Keyword(s):  
Molecular Docking ◽  
Opioid Receptor ◽  
Rank Order ◽  
Opioid Peptide ◽  
Mu Opioid Receptor ◽  
In Vitro Assays ◽  
Peptide Ligand ◽  
Mu Opioid ◽  
Peptide Analogues

The mu opioid receptor (MOR) is the primary target for analgesia of endogenous opioid peptides, alkaloids, synthetic small molecules with diverse scaffolds, and peptidomimetics. Peptide-based opioids are viewed as potential analgesics with reduced side effects and have received constant scientific interest over the years. This study focuses on three potent peptide and peptidomimetic MOR agonists, DALDA, [Dmt1]DALDA, and KGOP01, and the prototypical peptide MOR agonist DAMGO. We present the first molecular modeling study and structure–activity relationships aided by in vitro assays and molecular docking of the opioid peptide analogues, in order to gain insight into their mode of binding to the MOR. In vitro binding and functional assays revealed the same rank order with KGOP01 > [Dmt1]DALDA > DAMGO > DALDA for both binding and MOR activation. Using molecular docking at the MOR and three-dimensional interaction pattern analysis, we have rationalized the experimental outcomes and highlighted key amino acid residues responsible for agonist binding to the MOR. The Dmt (2′,6′-dimethyl-L-Tyr) moiety of [Dmt1]DALDA and KGOP01 was found to represent the driving force for their high potency and agonist activity at the MOR. These findings contribute to a deeper understanding of MOR function and flexible peptide ligand–MOR interactions, that are of significant relevance for the future design of opioid peptide-based analgesics.

Sign in / Sign up

Export Citation Format

Share Document