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Internet Electronic Journal of Molecular Design - IEJMD, ISSN 1538-6414, CODEN IEJMAT
| ABSTRACT - Internet Electron. J. Mol. Des. January 2002, Volume 1, Number 1, 37-51 |
Three-dimensional Pharmacophore Hypotheses of Octopamine Receptor Responsible for the
Inhibition of Sex-pheromone Production in Plodia interpunctella
Akinori Hirashima, Tomohiko Eiraku, Eiichi Kuwano, Eiji Taniguchi, and Morifusa Eto
Internet Electron. J. Mol. Des. 2002, 1, 37-51
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Abstract:
Our interest in octopaminergic agonists was aroused by the results of QSAR study using
various physicochemical parameters as descriptors or receptor surface models. Furthermore,
molecular modeling and conformational analysis were performed in Catalyst/Hypo to gain
a better knowledge of the interactions between octopaminergic antagonists and OAR3 in
order to understand identification of the conformations required for binding activity.
All experiments were conducted on a Silicon Graphics O2, running under the IRIX 6.5
operating system. Hypotheses generation and its functionality is available as part
of Molecular Simulations Incorporated's Catalyst/Hypo modeling environment. Molecules
were edited using the Catalyst 2D/3D visualizer. Three-dimensional pharmacophore
hypotheses were built from a set of 14 octopamine (OA) agonists responsible for the
inhibition of sex-pheromone production in Plodia interpunctella. Among the ten
chemical-featured models generated by program Catalyst/Hypo, hypotheses including
hydrogen-bond acceptor (HBA), hydrophobic (Hp), hydrophobic aromatic (HpAr), and
hydrophobic aliphatic (HpAl) features were considered to be important and predictive
in evaluating OA agonists. An HBA and four hydrophobic features are the minimum
components of an effective OA agonistic binding hypothesis, which resembles the
results of binding activity to locust OAR3. Active agonists mapped well onto all
the features of the hypothesis such as HBA, Hp, HpAr, and HpAl features. On the other
hand, inactive compounds lacking binding affinity were shown to be poorly capable of
achieving an energetically favorable conformation shared by the active molecules in
order to fit the 3D chemical feature pharmacophore models.
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