Exploring the deactivation mechanism of human β ₂ adrenergic receptor by accelerated molecular dynamic simulations.

ABSTRACT: The β ₂ adrenergic receptor (β₂AR), one of important members of the G protein coupled receptors (GPCRs), has been suggested as an important target for cardiac and asthma drugs. Two replicas of Gaussian accelerated molecular dynamics (GaMD) simulations are performed to explore the deactivation mechanism of the active β₂AR bound by three different substrates, including the agonist (P0G), antagonist (JTZ) and inverse agonist (JRZ). The simulation results indicate that the Gs protein is needed to stabilize the active state of the β₂AR. Without the Gs protein, the receptor could transit from the active state toward the inactive state. During the transition process, helix TM6 moves toward TM3 and TM5 in geometric space and TM5 shrinks upwards. T

SUBMITTER: Chen J 

PROVIDER: S-EPMC9468641 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature