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We recently published “Structural basis for nucleotide exchange in heterotrimeric G proteins” in Science.

G protein–coupled receptors (GPCRs) transmit diverse external signals into the cell. When activated by an outside stimulus, they bind to a G protein inside the cell and accelerate exchange of a bound guanosine diphosphate (GDP) nucleotide for guanosine triphosphate, which initiates intercellular signaling. Dror et al. used atomic-level molecular dynamics simulations to show how GPCRs enhance GDP release. The G protein is dynamic and frequently adopts a conformation that exposes GDP even without the receptor bound. GPCR binding to this conformation favors an additional structural rearrangement that favors GDP release. The authors confirmed these predictions experimentally using double electron-electron resonance spectroscopy.