Computational Analysis of Structure-Based Interactions for Novel H-1-Antihistamines

doi:10.3390/ijms17010129

	Computational Analysis of Structure-Based Interactions for Novel H-1-Antihistamines
	Yang, Yinfeng 1; Li, Yan 1; Pan, Yanqiu 1; Wang, Jinghui 1; Lin, Feng 1; Wang, Chao 1; Zhang, Shuwei 1; Yang, Ling 2
刊名	INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
	2016
卷号	17 期号:1
关键词	3d-qsar H-1-antihistamines Docking Molecular Dynamics
ISSN号	1422-0067
DOI	10.3390/ijms17010129
文献子类	Article
英文摘要	As a chronic disorder, insomnia affects approximately 10% of the population at some time during their lives, and its treatment is often challenging. Since the antagonists of the H-1 receptor, a protein prevalent in human central nervous system, have been proven as effective therapeutic agents for treating insomnia, the H-1 receptor is quite possibly a promising target for developing potent anti-insomnia drugs. For the purpose of understanding the structural actors affecting the antagonism potency, presently a theoretical research of molecular interactions between 129 molecules and the H-1 receptor is performed through three-dimensional quantitative structure-activity relationship (3D-QSAR) techniques. The ligand-based comparative molecular similarity indices analysis (CoMSIA) model (Q(2) = 0.525, R-ncv(2) = 0.891, R-pred(2) = 0.807) has good quality for predicting the bioactivities of new chemicals. The cross-validated result suggests that the developed models have excellent internal and external predictability and consistency. The obtained contour maps were appraised for affinity trends for the investigated compounds, which provides significantly useful information in the rational drug design of novel anti-insomnia agents. Molecular docking was also performed to investigate the mode of interaction between the ligand and the active site of the receptor. Furthermore, as a supplementary tool to study the docking conformation of the antagonists in the H-1 receptor binding pocket, molecular dynamics simulation was also applied, providing insights into the changes in the structure. All of the models and the derived information would, we hope, be of help for developing novel potent histamine H-1 receptor antagonists, as well as exploring the H-1-antihistamines interaction mechanism.
WOS关键词	HISTAMINE H-1 RECEPTOR ; CNS PENETRATING H-1-ANTIHISTAMINES ; MOLECULAR SIMILARITY INDEXES ; IN-SILICO ; SYSTEMS PHARMACOLOGY ; BIOLOGICAL-ACTIVITY ; CLINICAL-EVALUATION ; GENETIC ALGORITHM ; PRIMARY INSOMNIA ; DRUG DISCOVERY
WOS研究方向	Biochemistry & Molecular Biology ; Chemistry
语种	英语
出版者	MDPI AG
WOS记录号	WOS:000374583800123
内容类型	期刊论文
源URL	[http://cas-ir.dicp.ac.cn/handle/321008/170990]
专题	大连化学物理研究所_中国科学院大连化学物理研究所
通讯作者	Li, Yan
作者单位	1.Dalian Univ Technol, Dept Mat Sci & Chem Engn, Key Lab Ind Ecol & Environm Engn MOE, Dalian 116024, Peoples R China 2.Chinese Acad Sci, Grad Sch, Dalian Inst Chem Phys, Lab Pharmaceut Resource Discovery, Dalian 116023, Peoples R China
推荐引用方式 GB/T 7714	Yang, Yinfeng,Li, Yan,Pan, Yanqiu,et al. Computational Analysis of Structure-Based Interactions for Novel H-1-Antihistamines[J]. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES,2016,17(1).
APA	Yang, Yinfeng.,Li, Yan.,Pan, Yanqiu.,Wang, Jinghui.,Lin, Feng.,...&Yang, Ling.(2016).Computational Analysis of Structure-Based Interactions for Novel H-1-Antihistamines.INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES,17(1).
MLA	Yang, Yinfeng,et al."Computational Analysis of Structure-Based Interactions for Novel H-1-Antihistamines".INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES 17.1(2016).