Two Model System of the 1A-Adrenoceptor Docked with Selected Ligands

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• 作者：Wesley B. Asher ; Samantha N. Hoskins ; Leslie A. Slasor ; Deanna H. Morris ; Erika M. Cook ; Debra L. Bautista
• 刊名：Journal of Chemical Information and Modeling
• 出版年：2007
• 出版时间：September 2007
• 年：2007
• 卷：47
• 期：5
• 页码：1906 - 1912
• 全文大小：541K
• 年卷期：v.47,no.5(September 2007)
• ISSN：1549-960X

文摘

In this study, we have developed a two model system to mimic the active and inactive states of a G-proteincoupled receptor specifically the 1A adrenergic receptor. We have docked two agonists, epinephrine(phenylamine type) and oxymetazoline (imidazoline type), as well as two antagonists, prazosin and5-methylurapidil, into two 1A receptor models, active and inactive. The best docking complexes for bothagonists had hydrophilic interactions with D106, while neither antagonist did. Prazosin and oxymetazolinehad hydrophobic interactions with F308 and F312. We predict from our study that the active state is stabilizedby the interaction of F193 with I114, L197, V278, F281, and V282. The active state is further stabilized bythe interaction of F312 with L75, V79, and L80. We also predict that the inactive state of the receptor isstabilized by the interaction of F312 with W102, F288, and M292.