The glucocorticoid receptor (GR) is a ligand-regulated transcription factor which belongs to the nuclear receptor (NR) superfamily controlling gene expression giving rise to a variety of effects. The activation of GR is exploited to control inflammation. The majority of chronic inflammatory diseases can be treated with glucocorticosteroid agonists whose systemic use has been limited due to the onset of severe debilitating side effects like osteoporosis and suppression of HPA axis. In order to improve the pharmacological profile and the duration of action of the current ligands significant efforts have been aimed at gathering detailed information of their binding and unbinding mode. In this work we report our attempts to model the undocking process of glucocorticoid ligands bound to GR with the use of MD simulations and to relate these results to their binding kinetics.

Insight on the binding mode of glucocorticoid ligands

244th National Meeting (2012)

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