A virtual screening study of the acetylcholine binding protein using a relaxed-complex approach

被引：25

作者：

Babakhani, Arneh ^{[1
]}

Talley, Todd T. ^{[2
]}

Taylor, Palmer ^{[2
]}

McCammon, J. A. ^{[1
,2
,3
]}

机构：

[1] Univ Calif San Diego, Dept Chem & Biochem, La Jolla, CA 92093 USA

[2] Univ Calif San Diego, Dept Pharmacol, La Jolla, CA 92093 USA

[3] Univ Calif San Diego, Howard Hughes Med Inst, La Jolla, CA 92093 USA

来源：

COMPUTATIONAL BIOLOGY AND CHEMISTRY | 2009年 / 33卷 / 02期

基金：

美国国家卫生研究院;

关键词：

Acetylcholine binding protein; Nicotinic acetylcholine receptor; Relaxed-complex; Molecular dynamics; Docking; Virtual screening; MOLECULAR-DYNAMICS SIMULATIONS; RECEPTOR HOMOLOG ACHBP; CRYSTAL-STRUCTURE; CONFORMATIONAL-CHANGES; NICOTINIC RECEPTOR; DRUG DESIGN; TRYPTOPHAN FLUORESCENCE; FORCE-FIELD; LIGAND; REVEALS;

D O I：

10.1016/j.compbiolchem.2008.12.002

中图分类号：

Q [生物科学];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

The nicotinic acetylcholine receptor (nAChR) is a member of the ligand-gated ion channel family and is implicated in many neurological events. Yet, the receptor is difficult to target without high-resolution structures. In contrast, the structure of the acetylcholine binding protein (AChBP) has been solved to high resolution, and it serves as a surrogate structure of the extra-cellular domain in nAChR. Here we conduct a virtual screening study of the AChBP using the relaxed-complex method, which involves a combination of molecular dynamics simulations (to achieve receptor structures) and ligand docking. The library screened through comes from the National Cancer Institute, and its ligands show great potential for binding AChBP in various manners. These ligands mimic the known binders of AChBP; a significant subset docks well against all species of the protein and some distinguish between the various structures. These novel ligands could serve as potential pharmaceuticals in the AChBP/nAChR systems. Published by Elsevier Ltd

引用

页码：160 / 170

页数：11

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