Understanding the molecular basis of agonist/antagonist mechanism of human mu opioid receptor through gaussian accelerated molecular dynamics method

Yeng Tseng Wang*, Yang-Hsiang Chan

*Corresponding author for this work

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

The most powerful analgesic and addictive properties of opiate alkaloids are mediated by the μ opioid receptor (MOR). The MOR has been extensively investigated as a drug target in the twentieth century, with numerous compounds of varying efficacy being identified. We employed molecular dynamics and Gaussian accelerated molecular dynamics techniques to identify the binding mechanisms of MORs to BU72 (agonist) and β-funaltrexamine (antagonist). Our approach theoretically suggests that the 34 residues (Lys209–Phe221 and Ile301–Cys321) of the MORs were the key regions enabling the two compounds to bind to the active site of the MORs. When the MORs were in the holo form, the key region was in the open conformation. When the MORs were in the apo form, the key region was in the closed conformation. The key region might be responsible for the selectivity of new MOR agonists and antagonists.

Original languageEnglish
Article number7828
JournalScientific Reports
Volume7
Issue number1
DOIs
StatePublished - 1 Dec 2017

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