Characterization of binding site of closed-state KCNQ1 potassium channel by homology modeling, molecular docking, and pharmacophore identification

被引：24

作者：

Du, LP

Li, MY

Tsai, KC

You, QD ^{[1
]}

Xia, L

机构：

[1] China Pharmaceut Univ, Dept Med Chem, Nanjing 210009, Peoples R China

[2] Natl Tsing Hua Univ, Dept Life Sci, Inst Mol Med, Hsinchu 30013, Taiwan

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2005年 / 332卷 / 03期

关键词：

homology modeling; molecular docking; pharmacophore; KCNQ1 potassium channel; blockers;

D O I：

10.1016/j.bbrc.2005.04.165

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

This investigation was performed to assess the importance of interaction in the binding of blockers to KCNQ1 potassium using molecular modeling. This work could be considered made up by three main steps: ( 1) the construction of closed-state structure of KCNQ1 through homology modeling; (2) the automated docking of three blockers: IKS-142, L-735821, and BMS-IKS, using DOCK program; (3) the generation and validation of pharmacophore for KCNQ1 ligands using Catalyst/HypoGen. The obtained results highlight the hydrophobic or aromatic residues involved in S6 transmembrane domain and the base of the pore helix of KCNQ1, confirming the mutagenesis data and pharmacophore model, and giving new suggestions for the rational design of novel KCNQ1 ligands. (c) 2005 Elsevier Inc. All rights reserved.

引用

页码：677 / 687

页数：11

共 32 条

[11] The cardiac K+ channel KCNQ1 is essential for gastric acid secretion [J].