Docking to flexible nicotinic acetylcholine receptors: a validation study using the acetylcholine binding protein
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Docking to flexible nicotinic acetylcholine receptors : a validation study using the acetylcholine binding protein. / Sander, Tommy; Bruun, Anne T; Balle, Thomas.
I: Journal of Molecular Graphics and Modelling, Bind 29, Nr. 3, 2010, s. 415-424.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Docking to flexible nicotinic acetylcholine receptors
T2 - a validation study using the acetylcholine binding protein
AU - Sander, Tommy
AU - Bruun, Anne T
AU - Balle, Thomas
N1 - Copyright © 2010 Elsevier Inc. All rights reserved. Keywords: protein flexibility; molecular docking; ensemble generation; nicotinic; acetylcholine receptors>; nAChR; acetylcholine binding protein; AChBP
PY - 2010
Y1 - 2010
N2 - Computational docking to nicotinic acetylcholine receptors (nAChRs) and other members of the Cys-loop receptor family is complicated by the flexibility of the so-called C-loop. As observed in the large number of published crystal structures of the acetylcholine binding protein (AChBP), a structural surrogate and homology modeling template for the nAChRs, the conformation of this loop is controlled by the ligand present in the binding pocket. As part of the development of a protocol for unbiased docking to the nAChRs, we here present the results of docking of ligands with known binding modes to an AChBP ensemble with systematic variations in C-loop closure generated via a series of targeted geometry optimizations. We demonstrate the ability to correctly predict binding modes for 12 out of 15 ligands and induced degrees of C-loop closure for 14 out of 15 ligands. Our approach holds a promising potential for structure based drug discovery within nAChRs and related receptors.
AB - Computational docking to nicotinic acetylcholine receptors (nAChRs) and other members of the Cys-loop receptor family is complicated by the flexibility of the so-called C-loop. As observed in the large number of published crystal structures of the acetylcholine binding protein (AChBP), a structural surrogate and homology modeling template for the nAChRs, the conformation of this loop is controlled by the ligand present in the binding pocket. As part of the development of a protocol for unbiased docking to the nAChRs, we here present the results of docking of ligands with known binding modes to an AChBP ensemble with systematic variations in C-loop closure generated via a series of targeted geometry optimizations. We demonstrate the ability to correctly predict binding modes for 12 out of 15 ligands and induced degrees of C-loop closure for 14 out of 15 ligands. Our approach holds a promising potential for structure based drug discovery within nAChRs and related receptors.
KW - Former Faculty of Pharmaceutical Sciences
U2 - 10.1016/j.jmgm.2010.08.004
DO - 10.1016/j.jmgm.2010.08.004
M3 - Journal article
C2 - 20884263
VL - 29
SP - 415
EP - 424
JO - Journal of Molecular Graphics and Modelling
JF - Journal of Molecular Graphics and Modelling
SN - 1093-3263
IS - 3
ER -
ID: 22431800