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

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 dyna...

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Autores principales:	Yeng-Tseng Wang, Yang-Hsiang Chan
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/527fc220679949f9a8677f8a4f1658c3
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spelling	oai:doaj.org-article:527fc220679949f9a8677f8a4f1658c32021-12-02T16:06:01ZUnderstanding the molecular basis of agonist/antagonist mechanism of human mu opioid receptor through gaussian accelerated molecular dynamics method10.1038/s41598-017-08224-22045-2322https://doaj.org/article/527fc220679949f9a8677f8a4f1658c32017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-08224-2https://doaj.org/toc/2045-2322Abstract 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.Yeng-Tseng WangYang-Hsiang ChanNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Yeng-Tseng Wang Yang-Hsiang Chan Understanding the molecular basis of agonist/antagonist mechanism of human mu opioid receptor through gaussian accelerated molecular dynamics method
description	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.
format	article
author	Yeng-Tseng Wang Yang-Hsiang Chan
author_facet	Yeng-Tseng Wang Yang-Hsiang Chan
author_sort	Yeng-Tseng Wang
title	Understanding the molecular basis of agonist/antagonist mechanism of human mu opioid receptor through gaussian accelerated molecular dynamics method
title_short	Understanding the molecular basis of agonist/antagonist mechanism of human mu opioid receptor through gaussian accelerated molecular dynamics method
title_full	Understanding the molecular basis of agonist/antagonist mechanism of human mu opioid receptor through gaussian accelerated molecular dynamics method
title_fullStr	Understanding the molecular basis of agonist/antagonist mechanism of human mu opioid receptor through gaussian accelerated molecular dynamics method
title_full_unstemmed	Understanding the molecular basis of agonist/antagonist mechanism of human mu opioid receptor through gaussian accelerated molecular dynamics method
title_sort	understanding the molecular basis of agonist/antagonist mechanism of human mu opioid receptor through gaussian accelerated molecular dynamics method
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/527fc220679949f9a8677f8a4f1658c3
work_keys_str_mv	AT yengtsengwang understandingthemolecularbasisofagonistantagonistmechanismofhumanmuopioidreceptorthroughgaussianacceleratedmoleculardynamicsmethod AT yanghsiangchan understandingthemolecularbasisofagonistantagonistmechanismofhumanmuopioidreceptorthroughgaussianacceleratedmoleculardynamicsmethod
_version_	1718385146971815936

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

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