@article{e56adac1f5904af9a7bf299f3846d9d2,
title = "Acetylcholine binding protein (AChBP) as template for hierarchical in silico screening procedures to identify structurally novel ligands for the nicotinic receptors",
abstract = "Hierarchical in silico screening protocols against the agonist bound acetylcholine binding protein (AChBP) crystal structure were efficient in identifying novel chemotypes for AChBP and the human α7 receptor. Two hit structures were cocrystallized with AChBP revealing intermolecular cation-π interactions with loop C but lacking intermolecular hydrogen bonding. The compounds act as competitive α7 receptor antagonists and as non-competitive α4β2 receptor inhibitors. These results underline the usability of AChBP in structure-based in silico screening strategies in finding novel scaffolds for the α7 receptor, but also illustrates some limitations of using AChBP as bait to find competitive α4β2 receptor ligands and α7 receptor agonists.",
keywords = "Acetylcholine binding protein (AChBP), Crystallization, Cys-loop receptors, Docking, Electrophysiology, In silico screening, Ligand-gated ion channels (LGICs), Nicotinic acetylcholine receptors (nAChR), Virtual screening",
author = "Atilla Akdemir and Prakash Rucktooa and Aldo Jongejan and Elk, {Rene Van} and Sonia Bertrand and Sixma, {Titia K.} and Daniel Bertrand and Smit, {August B.} and Rob Leurs and {De Graaf}, Chris and {De Esch}, {Iwan J.P.}",
note = "Funding Information: We thank Chris Oostenbrink for fruitful discussions on our computational work, Dennis Verzijl, Gerold Bongers and Obbe Zuiderveld for discussions on our pharmacological work, and the Netherlands Organisation for Scientific Research (NWO) for providing financial support through a personal mozaiek-grant to A.A. We thank Robbie Joosten and Anastasis Perrakis for their help during the structure validation steps. The authors also wish to acknowledge financial support from the EU FP7 Neurocypres program (grant agreement n° HEALTH-F2-2007-202088). P.R. is supported by a long-term fellowship from the European Molecular Biology Organization.",
year = "2011",
month = oct,
day = "15",
doi = "https://doi.org/10.1016/j.bmc.2011.08.028",
language = "English",
volume = "19",
pages = "6107--6119",
journal = "Bioorganic and Medicinal Chemistry",
issn = "0968-0896",
publisher = "Elsevier Limited",
number = "20",
}