Computational investigation of the antagonism effect towards GluN2B-Containing NMDA receptor: Combined ligand-based and target-based approach

被引：5

作者：

Ma, Chao ^{[1
]}

Hu, Baichun ^{[1
]}

Zhang, Linkui ^{[1
]}

Zhao, Ying ^{[1
]}

Wang, Mingxing ^{[1
]}

Wang, Jian ^{[1
]}

Cheng, Maosheng ^{[1
]}

机构：

[1] Shenyang Pharmaceut Univ, Sch Pharmaceut Engn, Minist Educ, Key Lab Struct Based Drug Design & Discovery, 103 Wenhua Rd, Shenyang 110016, Liaoning, Peoples R China

来源：

JOURNAL OF MOLECULAR GRAPHICS & MODELLING | 2019年 / 86卷

基金：

中国国家自然科学基金;

关键词：

NMDA receptor; Neurodegenerative disorders; Molecular simulations; SUBUNIT; BINDING; BENZAMIDINES; DISCOVERY; AFFINITY; POTENT; SERIES; MOIETY;

D O I：

10.1016/j.jmgm.2018.10.009

中图分类号：

Q5 [生物化学];

学科分类号：

071010 ; 081704 ;

摘要：

The interaction of GluN2B-Containing NMDA Receptor with 18 antagonists were investigated by a combined ligand-based and target-based approach. First, two distinct pharmacophore models were generated for antagonists which cluster in two groups with Catalyst (HipHop module). The pharmacophore of "ifenprodil group" antagonists includes three hydrophobic groups, one H-bond donor and one H-bond acceptor, the pharmacophore of "EVT101 group" antagonists involves one aromatic ring, two hydrophobic groups and one H-bond acceptor. Docking results and pharmacophore model confrontation allow the pharmacodynamic characteristics to be weighted and structural information integrated. Which results in the proposal of two interaction models inside the GluN2B binding cavity for two groups of antagonists. The interaction model of "ifenprodil group" antagonists consists of one hydrophobic group, one H-bond donor, one H-bond acceptor and an aromatic ring, while on the other hand, the interaction model of "EVT101 group" antagonists includes three hydrophobic groups and an aromatic ring. (C) 2018 Elsevier Inc. All rights reserved,

引用

页码：95 / 105

页数：11

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