Structural Features and Ligand Selectivity for 10 Intermediates in the Activation Process of β₂-Adrenergic Receptor.

ABSTRACT: It has already been suggested by researchers that there should be multiple intermediate states in the activation process for G-protein-coupled receptors (GPCRs). However, the intermediate states are very short-lived and hardly captured by the experiments, leading to very limited understanding of their structural features and drug efficacies. In this work, a novel joint strategy of targeted molecular dynamics simulation, conventional molecular dynamics simulation, and virtual screening is developed to address the problems. The results from 10 intermediate conformations obtained from the work reveal that the ligand pocket is very unstable and fluctuates between the inactive state and the active one in the case of ligand-free, in particular for ECL2 as a gate-keeper of the ligand-binding. The

SUBMITTER: Liang T 

PROVIDER: S-EPMC6045391 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature