Computational analysis of the binding ability of heterocyclic and conformationally constrained epibatidine analogs in the neuronal nicotinic acetylcholine receptor

被引：0
作者：
Elena Soriano
José Marco-Contelles
Inés Colmena
Luis Gandía
机构：
[1] IQOG (CSIC),Laboratorio de Radicales Libres y Química Computacional (LRL/QC)
[2] Universidad Autónoma de Madrid,Instituto Teófilo Hernando de I+D del Medicamento, Departamento de Farmacologia, Facultad de Medicina
来源：
Molecular Diversity | 2010年 / 14卷
关键词：
Molecular docking; Nicotinic acetylcholine receptor (nAChR); Epibatidine; Epibatidine analogs; Pharmacophore;
D O I：
暂无
中图分类号：
学科分类号：
摘要：
One of the most critical issues on the study of ligand–receptor interactions in drug design is the knowledge of the bioactive conformation of the ligand. In this study, we describe a computational approach aimed at estimating the binding ability of epibatidine analogs to interact with the neuronal nicotinic acetylcholine receptor (nAChR) and get insights into the bioactive conformation. The protocol followed consists of a docking analysis and evaluation of pharmacophore parameters of the docked structures. On the basis of the biological data, the results have revealed that the docking analysis is able to predict active ligands, whereas further efforts are needed to develop a suitable and solid pharmacophore model.
引用
收藏
页码：201 / 211
页数：10
相关论文
共 117 条
  • [1] Gotti C(2006)Brain neuronal nicotinic receptors as new targets for drug discovery Curr Pharm Des 12 407-428
  • [2] Riganti L(2005)Refined structure of nicotinic receptors at 4 ANG resolution J Mol Biol 346 967-989
  • [3] Vailati S(2002)The nicotinic receptor ligand binding domain J Neurobiol 53 431-446
  • [4] Clementi F(2001)Crystal structure of an ACh-binding protein reveals the ligand-binding domain of nicotinic receptors Nature 411 269-276
  • [5] Unwin N(2002)Structural model of nicotinic acetylcholine receptor subtypes bound to a acetylcholine and nicotine BMC Struct Biol 2 1-8
  • [6] Sine SM(1970)Structure and activity of acetylcholine Nature 228 917-922
  • [7] Brejc K(1986)The ensemble approach to distance geometry: Application to the nicotinic pharmacophore J Med Chem 29 899-906
  • [8] van Dijk WJ(2001)An improved nicotinic pharmacophore and a stereoselective CoMFA-model for nicotinic agonists acting at the central nicotinic acetylcholine receptors labeled by [H-3]-N-methylcarbamylcholine J Comput Aided Mol Des 15 247-258
  • [9] Klaassen RV(2003)Synthesis, nicotinic acetylcholine receptor binding affinities, and molecular modeling of constrained epibatidine analogues J Med Chem 46 921-924
  • [10] Schuurmans M(2007)Central nicotinic receptors: structure, function, ligands, and therapeutic potential ChemMedChem 2 746-767
12345678910