Computational modeling study of human nicotinic acetylcholine receptor for developing new drugs in the treatment of alcoholism.

Interdisciplinary Sciences, Computational Life Sciences
Zeng-Jian HuWilliam Southerland

Abstract

Alcohol abuse and alcoholism are serious and costly problem in USA. Thus, the development of anti-alcoholism agents could be very significant. The understanding of the neurochemical basis underlying the addictive properties of drugs of abuse is imperative for the development of new pharmacological means to reverse the addictive state, prevent relapse or to reduce the intake of addictive compounds. The nicotinic acetylcholine receptors (nAChRs) are important therapeutic targets for various diseases. Recent studies have revealed that the alpha3beta2, alpha3beta3, and alpha6 subunits of nAChR protein family might be pharmacological targets for developing new drugs in the treatment of alcoholism. We have performed computational homology modeling of the alpha3beta2, alpha3beta3, and alpha6 subunits of human nACHRs based upon the recently determined crystal structure of the extracellular domain (ECD) of the mouse nAChR alpha1 subunit complexed with alpha-bungarotoxin at 1.94 A resolution. For comparison, we also built the ECD models of alpha4beta2, and alpha7 subunits of human nACHRs which are neurochemical targets for cessation of smoking. The three-dimensional (3D) models of the ECD of the monomer, and pentamer of these human nAChR...Continue Reading

References

Dec 5, 1993·Journal of Molecular Biology·A Sali, T L Blundell
Oct 15, 1998·Proceedings of the National Academy of Sciences of the United States of America·W ZhongD A Dougherty
Apr 9, 1999·Protein Engineering·B Rost
Jul 16, 1999·Neurochemistry International·T NarahashiK Nagata
Jun 8, 2001·Journal of Computer-aided Molecular Design·T J EwingI D Kuntz
Feb 28, 2002·BMC Structural Biology·Matthieu SchapiraMaxim Totrov
Feb 28, 2002·Proceedings of the National Academy of Sciences of the United States of America·Nicolas Le NovèreJean-Pierre Changeux
Aug 21, 2003·Bioorganic & Medicinal Chemistry·Guang-Yao GaoWing Ming Keung
Sep 25, 2003·British Journal of Pharmacology·Valeria CostaPaolo Carloni
Dec 4, 2003·Progress in Brain Research·Manickavasagom Alkondon, Edson X Albuquerque
Mar 17, 2004·Neuroscience and Biobehavioral Reviews·Anna Larsson, Jörgen A Engel
Jun 5, 2004·Biochemical and Biophysical Research Communications·Kuo-Chen Chou
Feb 11, 2005·Journal of Molecular Biology·Nigel Unwin
Jun 14, 2005·Nature Structural & Molecular Biology·Patrick H N CelieAugust B Smit
Aug 13, 2005·Molecular Membrane Biology·Shiva AmiriMark S P Sansom
Mar 24, 2006·Nature·Steven M Sine, Andrew G Engel
Jun 27, 2006·Alcohol and Alcoholism : International Journal of the Medical Council on Alcoholism·Elisabet JerlhagJörgen A Engel
Jul 14, 2006·BMC Bioinformatics·Elaine C MengThomas E Ferrin
Dec 7, 2006·Journal of Computer-aided Molecular Design·Demetri T MoustakasRobert C Rizzo
Mar 30, 2007·Computational Biology and Chemistry·D Yu MordvitsevV I Tsetlin
May 4, 2007·Journal of Computational Chemistry·Zengjian Hu, William Southerland
Feb 12, 2008·Trends in Pharmacological Sciences·Rainer Spanagel, Falk Kiefer
Mar 11, 2008·Journal of Molecular Graphics & Modelling·Maria KonstantakakiElias Eliopoulos
Mar 18, 2008·European Neuropsychopharmacology : the Journal of the European College of Neuropsychopharmacology·Elisabet JerlhagJörgen A Engel
Mar 21, 2008·Journal of Computational Chemistry·Sunhwan JoWonpil Im
May 30, 2008·Frontiers in Bioscience : a Journal and Virtual Library·Gregg B Wells
Aug 12, 2008·Biochemical Pharmacology·O K Steinlein, D Bertrand
Aug 14, 2008·Journal of Chemical Information and Modeling·Benjamin T MillerH Lee Woodcock
Oct 14, 2008·The Journal of Physical Chemistry. B·Esmael J HaddadianPei Tang
Nov 18, 2008·Bioorganic & Medicinal Chemistry Letters·Edwin G PérezGerald Zapata-Torres
Jan 8, 2009·Physiological Reviews·Edson X AlbuquerqueScott W Rogers

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Citations

Jul 19, 2011·Journal of Molecular Graphics & Modelling·Antoine TalyDelphine Joseph
Dec 20, 2011·Nicotine & Tobacco Research : Official Journal of the Society for Research on Nicotine and Tobacco·Elizabeth RalevskiIsmene Petrakis
Jun 4, 2013·Journal of Applied Biomaterials & Functional Materials·Giovanni S UgoliniMonica Soncini

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