Communication over the Network of Binary Switches Regulates the Activation of A2A Adenosine Receptor
“…These surfaces describe the more global domain‐like motions in the receptor without any information about conformational changes of individual residues. Recent studies have shown that conformational changes in a subset of residues, often called “microswitches”, manifest into macroscopic conformational changes indicative of activation/inactivation of the receptor . To characterize the changes in the conformational equilibria without prior knowledge of reaction coordinates, and to identify structural features such as the microswitches that are responsive to these changes, DIRECT‐ID analysis was performed using the trajectories from the five MD simulations.…”
Section: Resultsmentioning
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“…These surfaces describe the more global domain‐like motions in the receptor without any information about conformational changes of individual residues. Recent studies have shown that conformational changes in a subset of residues, often called “microswitches”, manifest into macroscopic conformational changes indicative of activation/inactivation of the receptor . To characterize the changes in the conformational equilibria without prior knowledge of reaction coordinates, and to identify structural features such as the microswitches that are responsive to these changes, DIRECT‐ID analysis was performed using the trajectories from the five MD simulations.…”
Section: Resultsmentioning
“…C, Table ). Several of these residues (E122 3.41 , T164 4.56 , Y326 7.53 ) have been identified through previous network information analysis methods and site‐directed mutational studies (see Table ) to behave as microswitches and participate in communication pathways that relay activation/inactivation information from the ligand binding pocket to the intracellular G‐protein binding regions. In addition, DIRECT‐ID identified residues that selectively responded to changes in conformational equilibria of the receptor mediated by only some of the ligands and not others.…”
Section: Resultsmentioning
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“…Unlike the conventional GPCRs that are deemed 'fine-tuned' to endogenous agonists such as hormones and neurotransmitters [16,17,18,19], ORs tend to be 'broadly tuned' to multiple odorant types. Conversely, a single odorant can also be recognized by multiple ORs.…”
Section: Introductionmentioning
“…And it also lead the opening of intracellular cavity that involves an outward movement of helices TM6 (about 10Å) and TM5 (about 2Å), for the subsequently transducer binding (Tehan et al, 2014;Manglik and Kruse, 2017). These rearrangement of the helices occur through series of changes in residue interactions called molecular switches Lee, Choi and Hyeon, 2015):…”
Section: Structural Insights Of the Activation Mechanismmentioning