G protein coupled receptors (GPCRs) play a crucial role in regulating signal recognition and transduction through their activation. The conformation transition in the activation pathway is of particular importance for their function. However, it has been poorly elucidated due to experimental difficulties in determining the conformations and the time limitation of @entity74 ( @entity74 ) simulation. Thus, in this work, we employed a @entity74 ( @entity74 ) simulation to study the activation process from an inactive structure to a fully active one for @entity2162 ( @entity2162 ). As a reference, 110 ns @entity74 simulations on wild @entity2162 and its @entity68554 mutant were also carried out. @entity74 results show that there is at least an intermediate conformation cluster in the activation process, evidenced by the principal component analysis and the structural and dynamic differences of some important motifs. It is noteworthy that the activation of the ligand binding site lags the G-protein binding site, displaying uncoupled correlation. Comparisons between the @entity74 and @entity74 results show that the @entity68554 mutation significantly speeds up ICL2 and key ionic lock to enter into the intermediate state, which to some extent facilitates the activation involved in the NPxxY, DRY region and the separation between @entity16544 and TM6. However, the contribution from the @entity68554 mutation to the activation of the ligand binding site could not be observed within the scale of 110 ns time. These observations could provide novel insights into previous studies for better understanding of the activation mechanism for @entity2162 .

Understanding the conformation transition in the activation pathway of XXXX via a targeted molecular dynamics simulation.

@entity68554 :: ('p|SUB|D|130|N', 'ProteinMutation') :: ['D130N'] @entity2162 :: ('154', 'Gene') :: ['b2 adrenergic receptor', 'b2AR'] @entity74 :: ('MESH:D030342', 'Disease') :: ['targeted molecular dynamic', 'conventional molecular dynamics', 'CMD', 'TMD'] @entity16544 :: ('7170', 'Gene') :: ['TM3']
@entity2162 :: (154,Gene) :: ['b2 adrenergic receptor']
