Molecular Dynamics: a tool to understand nuclear receptors

Nuclear receptors (NRs) are evolutionary conserved proteins whose encoding genes are expressed in the animal kingdom. The wide family of NRs counts more than 150 members, represented by both steroidal and non-steroidal receptors and by a multitude of orphan receptors, acting as intracellular ligand-inducible transcription factors able to respond to endogenous and exogenous chemicals, involved in the regulation of a wide variety of functions and in many related pathologies. NRs are characterized by a significant macro- and microflexibility affecting their structure, their interaction with natural substrates and ligands, and their activity. While experimental techniques are essentially devoted to elucidate the structural features of NRs, computational methodologies might provide valuable insights about the structure-activity relationship. In particular Molecular Dynamics based approaches represent nowadays the technique of choice for investigating the intrinsic dynamics of these molecules and relate the structural features and the conformational alterations of NRs and their ligands to the biological activity. A brief description of the available approaches known to provide the most reliable results and of some applications to real cases will be here provided.