[1P-39*] Structural dynamics of orexin2 receptor using molecular dynamics simulations
Orexinergic systems which comprise two peptide ligands, orexin-A and -B, and two G protein coupled receptors (GPCRs), orexin1 receptor (OX1R) and orexin2 receptor (OX2R), are involved in regulation of sleep wake rhythm etc. Such kinds of neurological process are caused by the GPCRs activation. It's a process where the ligand binding stabilizes the receptor conformation that allows for the G protein binding and the downstream signaling. However the mechanism of the activation remains unknown. Here, we investigated the dynamics of wild-type and mutants that are in the stable inactive state or the constitutively active by performing long-time all-atom molecular dynamics simulations. We performed over twenty several microsecond MD simulations of the wild-type and the mutants of the OX2R to extract the characteristics of the structural changes taking place in the active state. In this poster, we first show the results of the MD simulations and investigate the dynamics of the OX2R. Then, we discuss the implications in the activation of the GPCRs.