Imperial College London

DrRobertDickinson

Faculty of MedicineDepartment of Surgery & Cancer

Senior Lecturer
 
 
 
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Contact

 

+44 (0)20 7594 7633r.dickinson

 
 
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Location

 

Biophysics Group, Room 403Sir Ernst Chain BuildingSouth Kensington Campus

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Summary

 

Publications

Citation

BibTex format

@article{Bertaccini:2014:10.1021/cn500172e,
author = {Bertaccini, EJ and Dickinson, R and Trudell, JR and Franks, NP},
doi = {10.1021/cn500172e},
journal = {ACS Chemical Neuroscience},
pages = {1246--1252},
title = {Molecular modeling of a tandem two pore domain potassium channel reveals a putative binding Site for general anesthetics},
url = {http://dx.doi.org/10.1021/cn500172e},
volume = {5},
year = {2014}
}

RIS format (EndNote, RefMan)

TY  - JOUR
AB - Anesthetics are thought to mediate a portion of their activity via binding to and modulation of potassium channels. In particular, tandem pore potassium channels (K2P) are transmembrane ion channels whose current is modulated by the presence of general anesthetics and whose genetic absence has been shown to confer a level of anesthetic resistance. While the exact molecular structure of all K2P forms remains unknown, significant progress has been made toward understanding their structure and interactions with anesthetics via the methods of molecular modeling, coupled with the recently released higher resolution structures of homologous potassium channels to act as templates. Such models reveal the convergence of amino acid regions that are known to modulate anesthetic activity onto a common three- dimensional cavity that forms a putative anesthetic binding site. The model successfully predicts additional important residues that are also involved in the putative binding site as validated by the results of suggested experimental mutations. Such a model can now be used to further predict other amino acid residues that may be intimately involved in the target-based structure–activity relationships that are necessary for anesthetic binding.
AU - Bertaccini,EJ
AU - Dickinson,R
AU - Trudell,JR
AU - Franks,NP
DO - 10.1021/cn500172e
EP - 1252
PY - 2014///
SN - 1948-7193
SP - 1246
TI - Molecular modeling of a tandem two pore domain potassium channel reveals a putative binding Site for general anesthetics
T2 - ACS Chemical Neuroscience
UR - http://dx.doi.org/10.1021/cn500172e
UR - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000346682000014&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR - http://hdl.handle.net/10044/1/32932
VL - 5
ER -