Molecular modeling on solvent effect and interaction mechanism of fentanyl analogs to mu-opioid receptor

	Molecular modeling on solvent effect and interaction mechanism of fentanyl analogs to mu-opioid receptor
	Huang, XQ ; Jiang, HL; Luo, XM; Rong, SB ; Gu, JD; Tan, XJ ; Zhu, YC ; Chen, KX; Ji, RY
刊名	ACTA PHARMACOLOGICA SINICA
	2000-01
卷号	21 期号:1 页码:46-54
关键词	fentanyl molecular models solvents binding pocket structure-activity relationship
ISSN号	0253-9756
文献子类	Article
英文摘要	AIM: To do theoretical study about solvation effect and interaction mechanism of f'entanyl analogs (FA) to mu opioid receptor (mu OR). METHODS: Flexible docking (FlexiDock) was performed by using the possible active conformations of FA and optimized 3D structure of mu opioid receptor. Binding energies were calculated. Comparative molecular force field analysis (CoMFA) and quantitative structure activity relationship (QSAR) studies were carried out based on results of flexible docking. Solvation effects were considered by studying interaction of FA with water molecules. Partial least square (PLS) analysis was used to calculate regression equation for analgesic activities using binding energies as descriptive factor. RESULTS: 1) Binding conformations of these analogs derived by flexible docking were reasonable. 2) It was most possible for the FA to exist in water solution in the form of binding conformations. 3) Energetic calculation and QSAR analysis showed a good correlation between the calculated binding energies of FA and their analgesic activities. 4) Based on the 3D-model, the possible interaction mechanism of FA with mu opioid receptor can be illustrated reasonably. CONCLUSION: The nature of the correlation between the binding affinities and analgesic activities of FA was explained by our modeling result.
WOS关键词	THROMBIN INHIBITORS ; BINDING-SITE
WOS研究方向	Chemistry ; Pharmacology & Pharmacy
语种	英语
出版者	ACTA PHARMACOLOGICA SINICA
WOS记录号	WOS:000084710700007
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/274653]
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.Suzhou Univ, Dept Chem, Suzhou 215006, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 200031, Peoples R China
推荐引用方式 GB/T 7714	Huang, XQ,Jiang, HL,Luo, XM,et al. Molecular modeling on solvent effect and interaction mechanism of fentanyl analogs to mu-opioid receptor[J]. ACTA PHARMACOLOGICA SINICA,2000,21(1):46-54.
APA	Huang, XQ.,Jiang, HL.,Luo, XM.,Rong, SB.,Gu, JD.,...&Ji, RY.(2000).Molecular modeling on solvent effect and interaction mechanism of fentanyl analogs to mu-opioid receptor.ACTA PHARMACOLOGICA SINICA,21(1),46-54.
MLA	Huang, XQ,et al."Molecular modeling on solvent effect and interaction mechanism of fentanyl analogs to mu-opioid receptor".ACTA PHARMACOLOGICA SINICA 21.1(2000):46-54.