A Combination of Molecular Simulation and Network Methods for Analysis of Conformation Variation in Activation Process of β2 Adrenergic Receptor / 分析化学

ABSTRACT

To fill the urgent need of researches on the structure and function of proteins to obtain conformation information, we combined targeted molecular dynamics ( TMD) simulation with protein network methods to analyze conformation variations in the activation process of β2 adrenergic receptor. First, targeted MD was used to obtain the conformation resembles in the activation process, and then the protein network method was applied to identify the key residues and pathways in the activation process. The results indicate that the activa-tion process of β2 adrenergic receptor involves in the cooperation of all regions and the connector region of transmembrane helices is signaling hubs. In addition, the helix ends, including intracellular and extracellular loops, are the core areas. The pathway analysis reveals that there is more than one signaling pathway. All the pathways start from Ser204 of the ligand pocket and finally transmit to NPxxY or ICL2 region, which are depended on the different pathways. While the helix TMIII, TMV, TMVI are the important areas in all the pathways. The observations from the work provide valuable information at molecular level for unraveling the signal transduction mechanism associated with the activation process.