Exploring the deactivation mechanism of human β2 adrenergic receptor by accelerated molecular dynamic simulations

• DOI: 10.3389/fmolb.2022.972463
• Publication Date: 2022-08-30T06:53:38Z
• Authors: Jianzhong Chen; Jian Wang; Qingkai Zeng; Wei Wang; Haibo Sun; Benzheng Wei
• Keywords: 0301 basic medicine; 03 medical and health sciences; G protein-coupled receptors; QH301-705.5; Molecular Biosciences; deactivation mechanism; free energy landscapes; Biology (General); β2 adrenergic receptor; GaMD simulations

The β2 adrenergic receptor (β2AR), one of important members the G protein coupled receptors (GPCRs), has been suggested as an target for cardiac and asthma drugs. Two replicas Gaussian accelerated molecular dynamics (GaMD) simulations are performed to explore deactivation mechanism active β2AR bound by three different substrates, including agonist (P0G), antagonist (JTZ) inverse (JRZ). simulation results indicate that Gs is needed stabilize state β2AR. Without protein, could transit from toward inactive state. During transition process, helix TM6 moves TM3 TM5 in geometric space shrinks upwards. intermediate captured during process one, moreover changes hydrophobic interaction networks between helixes TM3, TM5, formation a salt bridge residues Arg3.50 Glu6.30 drive process. We expect this finding can provide energetic basis further understanding function roles