Skip Navigation



PEDS Advance Access published online on June 26, 2007
Protein Engineering Design and Selection, doi:10.1093/protein/gzm029
This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow All Versions of this Article:
20/7/353    most recent
gzm029v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Amiri, S.
Right arrow Articles by Biggin, P. C.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Amiri, S.
Right arrow Articles by Biggin, P. C.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author 2007. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org

Molecular dynamics studies of AChBP with nicotine and carbamylcholine: the role of water in the binding pocket

Shiva Amiri, Mark S.P. Sansom and Philip C. Biggin1

Structural Bioinformatics and Computational Biochemistry, Department of Biochemistry, The University of Oxford, South Parks Road, Oxford OX1 3QU, UK

1 To whom correspondence should be addressed. E-mail: philip.biggin{at}bioch.ox.ac.uk

The acetylcholine-binding protein (AChBP) is homologous to the ligand-binding domain of the nicotinic acetylcholine receptor (nAChR) and other members of the Cys-loop family of neurotransmitter receptors. The high-resolution X-ray structures of AChBP mean it has been used as a model from which to understand agonist and antagonist binding to nAChRs. We present here a molecular dynamics (MD) study of AChBP with nicotine and carbamylcholine bound. Our results suggest that the ligand imposes rigidity on the binding pocket residues. The simulations also suggest that the protein undergoes breathing motions with respect to the five-fold axis, a motion that has been postulated to be related to gating in the nAChR. We analyzed the behaviour of the water molecules in and around the binding site and found that they occupied five distinct sites within the binding pocket. Water occupied these sites in the absence of ligand, but the presence of ligand increased the probability that a water molecule would be found in these sites. Finally, we demonstrate how the positions of these waters might be used in the design of new ligands by comparing the positions of these sites with other recent structures.

Keywords: nicotinic acetylcholine receptor/computational/conformational change/cys-loop receptor/simulation

Received April 13, 2007; revised April 13, 2007; accepted April 26, 2007.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 Mol. Pharmacol.Home page
L. M. Sharkey and C. Czajkowski
Individually Monitoring Ligand-Induced Changes in the Structure of the GABAA Receptor at Benzodiazepine Binding Site and Non-Binding-Site Interfaces
Mol. Pharmacol., July 1, 2008; 74(1): 203 - 212.
[Abstract] [Full Text] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.