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题名: Studies of H4R antagonists using 3D-QSAR, molecular docking and molecular dynamics
作者: Liu, Jing1;  Li, Yan1;  Zhang, Hui-Xiao1;  Zhang, Shu-Wei1;  Yang, Ling2
关键词: 3D-QSAR ;  H4R antagonist ;  CoMFA ;  CoMSIA ;  MD ;  Docking
刊名: JOURNAL OF MOLECULAR MODELING
发表日期: 2012-03-01
DOI: 10.1007/s00894-011-1137-x
卷: 18, 期:3, 页:991-1001
收录类别: SCI
文章类型: Article
类目[WOS]: Biochemistry & Molecular Biology ;  Biophysics ;  Chemistry, Multidisciplinary ;  Computer Science, Interdisciplinary Applications
研究领域[WOS]: Biochemistry & Molecular Biology ;  Biophysics ;  Chemistry ;  Computer Science
英文摘要: Three-dimensional quantitative structure-activity relationship studies were performed on a series of 88 histamine receptor 4 (H4R) antagonists in an attempt to elucidate the 3D structural features required for activity. Several in silico modeling approaches, including comparative molecular field analysis (CoMFA), comparative similarity indices analysis (CoMSIA), molecular docking, and molecular dynamics (MD), were carried out. The results show that both the ligand-based CoMFA model (Q(2)=0.548, R-ncv(2)=0.870, R-pre(2)=0.879, SEE=0.410, SEP=0.386) and the CoMSIA model (Q(2)=0.526, R-ncv(2)=0.866, R-pre(2)=0.848, SEE=0.416, SEP=0.413) are acceptable, as they show good predictive capabilities. Furthermore, a combined analysis incorporating CoMFA, CoMSIA contour maps and MD results shows that (1) compounds with bulky or hydrophobic substituents at positions 4-6 in ring A (R2 substituent), positively charged or hydrogen-bonding (HB) donor groups in the R1 substituent, and hydrophilic or HB acceptor groups in ring C show enhanced biological activities, and (2) the key amino acids in the binding pocket are TRP67, LEU71, ASP94, TYR95, PHE263 and GLN266. To our best knowledge, this work is the first to report the 3D-QSAR modeling of these H4R antagonists. The conclusions of this work may lead to a better understanding of the mechanism of antagonism and aid in the design of new, more potent H4R antagonists.
关键词[WOS]: HISTAMINE H-4 RECEPTOR ;  BINDING MODE ;  DRUG DESIGN ;  INHIBITORS ;  COMFA ;  COMSIA ;  LIGANDS ;  QSAR ;  IDENTIFICATION ;  SIMULATION
语种: 英语
WOS记录号: WOS:000303539500016
Citation statistics: 
内容类型: 期刊论文
URI标识: http://cas-ir.dicp.ac.cn/handle/321008/142847
Appears in Collections:中国科学院大连化学物理研究所_期刊论文

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作者单位: 1.Dalian Univ Technol, Dept Mat Sci & Chem Engn, Dalian 116012, Liaoning, Peoples R China
2.Chinese Acad Sci, Grad Sch, Dalian Inst Chem Phys, Lab Pharmaceut Resource Discovery, Dalian 116023, Liaoning, Peoples R China

Recommended Citation:
Liu, Jing,Li, Yan,Zhang, Hui-Xiao,et al. Studies of H4R antagonists using 3D-QSAR, molecular docking and molecular dynamics[J]. JOURNAL OF MOLECULAR MODELING,2012,18(3):991-1001.
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