G protein-coupled receptors (GPCRs) are the largest class of membrane proteins and are involved in a wide variety of physiological processes, making them targets of around 30-50% of medicinal drugs. The A2A adenosine receptor is activated by extracellular adenosine, and activates the stimulatory G-protein Gs. To better understand the activation cycle, 5 microsecond simulations were performed for the A2A adenosine receptor bound to NECA in two states: with a “mini G protein” bound, and without G protein. Analysis of helix RMSD distributions suggests a special role for helix 3 in the return of the protein to the inactive state. Analysis of contacts formed and broken during the simulation between the mini G protein and the receptor, and comparison to the crystal structure identifies several new contacts formed between the third intracellular loop and the mini G protein and suggests the conformational change of the mini G protein after GDP unbinds from its binding interface. Pathways of coupled side chain conformations between the mini G protein and the ligand binding site were identified by a mutual information analysis.

A2A adenosine receptor activation studied by all-atom simulation

Macromolecular Chemistry: The Second Century

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ACS Spring 2020 National Meeting & Expo

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.