کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
9590522 | 1507002 | 2005 | 9 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
A quantitative structure-activity relationship investigation into agonist binding at GABAC receptors
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کلمات کلیدی
موضوعات مرتبط
مهندسی و علوم پایه
شیمی
شیمی تئوریک و عملی
پیش نمایش صفحه اول مقاله
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چکیده انگلیسی
The quantitative structure-activity relationship (QSAR) model constructed in this work represents the first quantitative investigation into agonist binding at GABAC receptors. This model is based upon the three-dimensional structures of (γ-aminobutyric acid (GABA) and 12 other biologically active GABA analogues. These structures are obtained by geometry optimization and conformational exploration at MP2/6-31+G* within the conductor-like screening solvation model (COSMO). The biological activity data are obtained from previous two-electrode voltage clamp electrophysiological studies on recombinant GABAC Ï1 receptors expressed in Xenopus laevis oocytes. A QSAR model to predict GABAC agonist binding is constructed from molecular superposition data, generated by least-squares superposition of the stable aqueous phase conformations of GABA and its known biologically active analogues to the bioactive conformation of TACA, the most potent GABAC receptor agonist. A significant relationship is found between the root-mean-squared deviation in atomic position for the stable conformer of each GABA analogue most closely fitting the template TACA structure and the natural log of the normalized biological activity (R2=0.91, p<0.0001), On the basis of molecular superposition and QSAR results, a pharmacophore model describing three-dimensional features and key interactions at the GABAC receptor binding site is proposed. As there exists no direct experimental knowledge of structure of the GABAC binding site, this approach provides a feasible and reliable alternative to gain insight into its three-dimensional structure.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Molecular Structure: THEOCHEM - Volume 755, Issues 1â3, 30 November 2005, Pages 81-89
Journal: Journal of Molecular Structure: THEOCHEM - Volume 755, Issues 1â3, 30 November 2005, Pages 81-89
نویسندگان
Deborah L. Crittenden, Mary Chebib, Meredith J.T. Jordan,