Three-dimensional pharmacophore hypotheses were built on the basis of a set of nine octopamine (OA) agonists responsible for the inhibition of sex- pheromone production in Helicoverpa armigera. Of the 10 models generated by the program Catalyst/Hypo, hypotheses including hydrogen-bond acceptor (HBA), hydrophobic (Hp), and hydrophobic aliphatic (HpAl) features were considered important and predictive in evaluating OA agonists. An HBA and four hydrophobic features are the minimum components of an effective OA agonist- binding hypothesis, which resembles the results of binding activity to locust OAR3. Active agonists mapped well onto all of the features of the hypothesis, such as HBA, Hp, 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. Those hypotheses are considered useful in designing new leads for more active compounds. Further research on the comparison of models from agonists may help elucidate the mechanisms of OA receptor-ligand interactions.
!!!All Science Journal Classification (ASJC) codes
- コンピュータ グラフィックスおよびコンピュータ支援設計