Activation-Induced Reorganization of Energy Transport Networks in the β2 Adrenergic Receptor.

We compute energy exchange networks (EENs) through the β2 adrenergic receptor (β2AR), a G-protein coupled receptor (GPCR), in inactive and active states, based on the results of molecular dynamics simulations of this membrane bound protein. We introduce a new definition for the reorganization of EENs upon activation that depends on the relative change in rates of energy transfer across noncovalent contacts throughout the protein. On the basis of the reorganized network that we obtain for β2AR upon activation, we identify a branched pathway between the agonist binding site and the cytoplasmic region, where a G-protein binds to the receptor when activated. The pathway includes all of the motifs containing molecular switches previously identified as contributing to the allosteric transition of β2AR upon agonist binding. EENs and their reorganization upon activation are compared with structure-based contact networks computed for the inactive and active states of β2AR.