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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
16
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pubmed:dateCreated |
2005-8-4
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pubmed:abstractText |
The homology models of the extracellular domains of the neuronal alpha4beta2 (pdb code: 1ole) and ganglionic alpha3beta4 (pdb code: 1olf) rat nicotinic acetylcholine receptor (nAChR) subtypes were refined and energetically minimized. In this work, a series of nAChR ligands (1-15) were docked into the modeled binding cavity of both receptors. High-affinity, toxic ligands such as epibatidine (1) and dechloroepibatidine (2) docked into cluster 1 with the charged tertiary amino group, forming a pi-cation interaction with Trp 147 on the (+) side of the alpha4 subunit and establishing a characteristic H-bond with the Lys 77 on the (-) side of the beta2 subunit. The nontoxic ligands such as 33bMet (3), (S)-A-85380 (4), and acetylcholine (6) docked into cluster 2 with the same pi-cation interaction but with the rest of the molecule occupying a different moiety of the binding pocket. Molecular docking into the alpha3beta4 subtype showed that both enantiomers of 1 (1a and 1b) are representative templates for ligands with affinity toward this ganglionic nAChR subtype. The ranking scores of the docked molecules confirm the existence of structure-dependent subtype selectivity and shed light on the design of specific and selective alpha4beta2 nAChR subtype ligands.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/3-(2-(pyrrolidinyl)methoxy)pyridine,
http://linkedlifedata.com/resource/pubmed/chemical/3-methyl-5-(1-methyl-2-pyrrolidinyl)...,
http://linkedlifedata.com/resource/pubmed/chemical/A 85380,
http://linkedlifedata.com/resource/pubmed/chemical/Acetylcholine,
http://linkedlifedata.com/resource/pubmed/chemical/Azetidines,
http://linkedlifedata.com/resource/pubmed/chemical/Bicyclo Compounds, Heterocyclic,
http://linkedlifedata.com/resource/pubmed/chemical/Isoxazoles,
http://linkedlifedata.com/resource/pubmed/chemical/Ligands,
http://linkedlifedata.com/resource/pubmed/chemical/Nerve Tissue Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Pyridines,
http://linkedlifedata.com/resource/pubmed/chemical/Pyrrolidines,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Nicotinic,
http://linkedlifedata.com/resource/pubmed/chemical/epibatidine,
http://linkedlifedata.com/resource/pubmed/chemical/nicotinic receptor alpha3beta4,
http://linkedlifedata.com/resource/pubmed/chemical/nicotinic receptor alpha4beta2
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
0022-2623
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
11
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pubmed:volume |
48
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
5123-30
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:16078832-Acetylcholine,
pubmed-meshheading:16078832-Animals,
pubmed-meshheading:16078832-Azetidines,
pubmed-meshheading:16078832-Bicyclo Compounds, Heterocyclic,
pubmed-meshheading:16078832-Binding, Competitive,
pubmed-meshheading:16078832-Binding Sites,
pubmed-meshheading:16078832-Brain,
pubmed-meshheading:16078832-Cell Line,
pubmed-meshheading:16078832-Crystallography, X-Ray,
pubmed-meshheading:16078832-Hydrogen Bonding,
pubmed-meshheading:16078832-Isoxazoles,
pubmed-meshheading:16078832-Ligands,
pubmed-meshheading:16078832-Mice,
pubmed-meshheading:16078832-Models, Molecular,
pubmed-meshheading:16078832-Nerve Tissue Proteins,
pubmed-meshheading:16078832-Oocytes,
pubmed-meshheading:16078832-Pyridines,
pubmed-meshheading:16078832-Pyrrolidines,
pubmed-meshheading:16078832-Rats,
pubmed-meshheading:16078832-Receptors, Nicotinic,
pubmed-meshheading:16078832-Snails,
pubmed-meshheading:16078832-Stereoisomerism,
pubmed-meshheading:16078832-Thermodynamics,
pubmed-meshheading:16078832-Xenopus
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pubmed:year |
2005
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pubmed:articleTitle |
Ligand selectivity for the acetylcholine binding site of the rat alpha4beta2 and alpha3beta4 nicotinic subtypes investigated by molecular docking.
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pubmed:affiliation |
Center for Radiopharmaceutical Sciences, Swiss Federal Institute of Technology Zurich, Paul Scherrer Institute, Rämistrasse 100,CH-8091 Zürich, Switzerland.
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pubmed:publicationType |
Journal Article,
In Vitro
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