标题:Structural Requirements of N-Substituted Spiropiperidine Analogues as Agonists of Nociceptin/Orphanin FQ Receptor
作者:Bao, Pingping; Zhang, Xiaole; Ren, Hong; Li, Yan; Mu, Zulin; Zhang, Shuwei; Li, Guohui; Yang, Ling
作者机构:[Bao, Pingping; Li, Yan; Mu, Zulin; Zhang, Shuwei] Dalian Univ Technol, Dept Mat Sci & Chem Engn, Dalian 116023, Liaoning, Peoples R China.; [Zhang, 更多
通讯作者:Li, Y
通讯作者地址:[Li, Y]Dalian Univ Technol, Dept Mat Sci & Chem Engn, Dalian 116023, Liaoning, Peoples R China.
来源:INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
出版年:2011
卷:12
期:12
页码:8961-8981
DOI:10.3390/ijms12128961
关键词:NOP agonist; N-substituted spiropiperidine analogues; 3D-QSAR; molecular; docking; molecular dynamics
摘要:The nociceptin/orphanin FQ (NOP) receptor is involved in a wide range of biological functions, including pain, anxiety, depression and drug abuse. Especially, its agonists have great potential to be developed into anxiolytics. In this work, both the ligand- and receptor-based three-dimensional quantitative structure-activity relationship (3D-QSAR) studies were carried out using comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) techniques on 103 N-substituted spiropiperidine analogues as NOP agonists. The resultant optimal ligand- based CoMSIA model exhibited Q(2) of 0.501, R-ncv(2) of 0.912 and its predictive ability was validated by using an independent test set of 26 compounds which gave R-pred(2) value of 0.818. In addition, docking analysis and molecular dynamics simulation (MD) were also applied to elucidate the probable binding modes of these agonists. Interpretation of the 3D contour maps, in the context of the topology of the active site of NOP, provided insight into the NOP-agonist interactions. The information obtained from this work can be used to accurately predict the binding affinity of related agonists and also facilitate the future rational design of novel agonists with improved activity.
收录类别:SCOPUS;SCIE
WOS核心被引频次:4
Scopus被引频次:3
资源类型:期刊论文
原文链接:https://www.scopus.com/inward/record.uri?eid=2-s2.0-84055211772&doi=10.3390%2fijms12128961&partnerID=40&md5=f6594d0990d832041c4ca77a74081d3c
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