Study on mechanism of interaction of nociceptin and opioids binding with opioid receptor-like 1 receptor

	Study on mechanism of interaction of nociceptin and opioids binding with opioid receptor-like 1 receptor
	Huang, XQ ; Jiang, HL; Luo, XM; Chen, KX; Zhu, YC ; Ji, RY ; Cao, Y
刊名	ACTA PHARMACOLOGICA SINICA
	2000-06
卷号	21 期号:6 页码:536-546
关键词	nociceptin lofentanyl etorphine ORL1 receptor molecular docking binding energy
ISSN号	0253-9756
文献子类	Article
英文摘要	AIM: To study the mechanism of interaction of nociceptin and opioids with ORL1 receptor. METHODS: Molecular dynamics study was carried out before nociceptin was manually docked into the binding site of ORL1 receptor; DOCK4. 0 program was applied to dock four stereoisomers of lofentanyl and etorphine into the binding pocket of ORL1 receptor. Binding energies were calculated, the relationship between binding energy and binding affinity was studied. RESULTS: Nociceptin fits well into the binding pocket, the N-terminal FGGF tetrapeptide is located in the inner region of the binding cavity, the nociceptin (5 - 7) interacts with the conservatively variable residues near the other end of binding pocket, and maybe determines selectivity of ORL1 receptor over dynorphin A, the positively charged core of nociceptin (8-13) binds predominantly with negatively charged EL-2 loop, which is thought to be able to mediate receptor activation. The shortest fully active analogue of nociceptin (1-13) is also discussed. The main difference between these two opioids and nociceptin exists in the kinds and the number of conserved and variable residues in the binding pocket and thereafter in the strength of their interaction. Prediction for binding affinities of four stereoisomers of lofentanyl has been performed based on their binding energies, the similar pharmacophore of lofentanyl and other fentanyl analogs, and the good correlation between binding energies and their experimental binding affinities (- logK(i) values). CONCLUSION: Ligand docking results from this study are helpful in clarifying experimental observations of ligands interaction with opioid receptors, thus furthering biological investigations.
WOS关键词	DYNORPHIN-A ; ORPHANIN FQ ; AGONIST ; ORL1
WOS研究方向	Chemistry ; Pharmacology & Pharmacy
语种	英语
出版者	ACTA PHARMACOLOGICA SINICA
WOS记录号	WOS:000087561300008
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/274613]
专题	中国科学院上海药物研究所
通讯作者	Chen, KX
作者单位	1.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 200031, Peoples R China 2.Suzhou Univ, Dept Chem, Suzhou 215006, Peoples R China
推荐引用方式 GB/T 7714	Huang, XQ,Jiang, HL,Luo, XM,et al. Study on mechanism of interaction of nociceptin and opioids binding with opioid receptor-like 1 receptor[J]. ACTA PHARMACOLOGICA SINICA,2000,21(6):536-546.
APA	Huang, XQ.,Jiang, HL.,Luo, XM.,Chen, KX.,Zhu, YC.,...&Cao, Y.(2000).Study on mechanism of interaction of nociceptin and opioids binding with opioid receptor-like 1 receptor.ACTA PHARMACOLOGICA SINICA,21(6),536-546.
MLA	Huang, XQ,et al."Study on mechanism of interaction of nociceptin and opioids binding with opioid receptor-like 1 receptor".ACTA PHARMACOLOGICA SINICA 21.6(2000):536-546.