DOCKING STUDIES OF BENZODIAZEPINES AS A POSITIVE ALLOSTERIC MODULATOR OF GABA-A RECEPTOR
Keywords:
QSAR, Docking, Gama Amino Butyric Acid agonist, GABA receptor, Benzodiazepine derivatives.Abstract
Benzodiazepine is an antixylotic agent , induce and maintain sleep, reduce seizures, and induce conscious sedation. It acts as a positive allosteric modulator of GABAA receptor. The binding of benzodiazepine analogues to this allosteric modulatory site enhances the affinity of GABA (Gama amino butyric acid) for the agonist recognition site. In the present work, docking studies has been performed to understand the effect of substitution and structural features on the GABA agonist activity of Benzodiazepines and to study the interactions of benzodiazepine derivatives with the binding sites on GABAA receptor. In present study structure based drug design is applied to visualize the structural requirement of the compounds. Our previous QSAR model (r= 0.995, r2 = 0.990, Std deviation s = 0.0636) reveled that the descriptors Surface Tension, Molar Volume and Parachor played an important role in binding affinity of Benzodiazepines derivatives to GABAA receptor . A docking study has been performed on the same set of compounds to re-examine our previous findings. The hypothesis has also been validated with an experimental data. The outcome of the present study may be useful in the designing of more potent Benzodiazepine analogue as an antixylotic agents.
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