Dopamine D-1 receptor and serotonin 5-HT1A receptor agonist effects of the natural product (-)-stepholidine: molecular modelling and dynamics simulations

doi:10.1080/08927022.2012.679619

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	Dopamine D-1 receptor and serotonin 5-HT1A receptor agonist effects of the natural product (-)-stepholidine: molecular modelling and dynamics simulations
	Gong, Yunguo 2,3; Fu, Wei 3; Chen, Kaixian1,3
刊名	MOLECULAR SIMULATION
	2012
卷号	38 期号:12 页码:970-979
关键词	molecular dynamics l-SPD (l-stepholidine) G-protein-coupled receptor (GPCR) D-1 receptor 5-HT1A receptor
ISSN号	0892-7022
DOI	10.1080/08927022.2012.679619
文献子类	Article
英文摘要	In this study, by homology modelling and molecular dynamics (MD) simulation, models of l-stepholidine (l-SPD) activating the 5-HT1A and D-1 receptors were constructed. In 100-ns MD simulations, the D-1 and 5-HT1A receptors were activated by the partial agonist l-SPD, conforming with the global toggle switch activation model and the sequential activation model. The residues Y-7.53 and Y-5.58 swing significantly between different transmembrane (TM) domains after activation. Similarities between D-1 and 5-HT1A included (1) the outward motion of TM-5; (2) the ionic lock was independent of the tilt of TM-6 and (3) there was an apparent bending of TM-6, and the ring of l-SPD formed strong pi-pi interactions with residue W-6.48. Differences between the two included the following: (1) in 5-HT1A, l-SPD formed a hydrogen bond with Ala172(5.46) of TM-5, and the intracellular end of TM-5 moved outward slowly; that hydrogen bond did not form with the D-1 receptor; (2) l-SPD formed stronger interactions with D-3.32 and W-6.48 in the D-1 receptor than in the 5-HT1A receptor and (3) the hydrogen bonding network was somewhat different in SPD-5-HT1A and SPD-D-1 receptors. We propose the interaction between l-SPD and D-3.32 or/and W-6.48 is the original driving force during the whole activation process.
WOS关键词	PROTEIN-COUPLED RECEPTOR ; 2ND EXTRACELLULAR LOOP ; TOGGLE SWITCH MODEL ; CRYSTAL-STRUCTURE ; MECHANOSENSITIVE CHANNEL ; CONFORMATIONAL STATES ; L-STEPHOLIDINE ; ACTIVATION ; RHODOPSIN ; BINDING
WOS研究方向	Chemistry ; Physics
语种	英语
出版者	TAYLOR & FRANCIS LTD
WOS记录号	WOS:000308864000004
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/278243]
专题	药物发现与设计中心
通讯作者	Fu, Wei
作者单位	1.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China 2.Van Andel Res Inst, Grand Rapids, MI 49503 USA; 3.Fudan Univ, Sch Pharm, Shanghai 201203, Peoples R China;
推荐引用方式 GB/T 7714	Gong, Yunguo,Fu, Wei,Chen, Kaixian. Dopamine D-1 receptor and serotonin 5-HT1A receptor agonist effects of the natural product (-)-stepholidine: molecular modelling and dynamics simulations[J]. MOLECULAR SIMULATION,2012,38(12):970-979.
APA	Gong, Yunguo,Fu, Wei,&Chen, Kaixian.(2012).Dopamine D-1 receptor and serotonin 5-HT1A receptor agonist effects of the natural product (-)-stepholidine: molecular modelling and dynamics simulations.MOLECULAR SIMULATION,38(12),970-979.
MLA	Gong, Yunguo,et al."Dopamine D-1 receptor and serotonin 5-HT1A receptor agonist effects of the natural product (-)-stepholidine: molecular modelling and dynamics simulations".MOLECULAR SIMULATION 38.12(2012):970-979.