文献类型：期刊文献

英文题名：Computational investigation of interactions between human H2 receptor and its agonists

作者：Sun, Xianqiang[1]; Li, Yaozong[1]; Li, Weihua[1]; Xu, Zhejun[1]; Tang, Yun[1]

机构：[1] Department of Pharmaceutical Sciences, School of Pharmacy, East China University of Science and Technology, 130 Meilong Road, Shanghai 200237, China

年份：2011

卷号：29

期号：5

起止页码：693

外文期刊名：Journal of Molecular Graphics and Modelling

收录：EI(收录号：20110713659133)

语种：英文

外文关键词：Computational chemistry - Molecular modeling - Molecular dynamics - Diagnosis - Search engines - Pharmacodynamics

摘要：Type 2 histamine receptor (H2R) is widely distributed in the body. Its main function is modulating the secretion of gastric acid. Most gastric acid-related diseases are closely associated with it. In this study, a combination of pharmacophore modeling, homology modeling, molecular docking and molecular dynamics methods were performed on human H2R and its agonists to investigate interaction details between them. At first, a pharmacophore model of H2R agonists was developed, which was then validated by QSAR and database searching. Afterwards, a model of the H 2R was built utilizing homology modeling method. Then, a reference agonist was docked into the receptor model by induced fit docking. The 'induced' model can dramatically improve the recovery ratio from 46.8% to 69.5% among top 10% of the ranked database in the simulated virtual screening. The pharmocophore model and the receptor model matched very well each other, which provided valuable information for future studies. Asp98, Asp186 and Tyr190 played key roles in the binding of H2R agonists, and direct interactions were observed between the three residues and agonists. Residue Tyr250 could also form a hydrogen bond with H2R agonists. These findings would be very useful for the discovery of novel and potent H 2R agonists. ? 2010 Elsevier Inc.