Extended Data Fig. 8: Molecular Dynamics simulations reveal how MOR–G protein conformations dictate AHD and GDP dynamics.

MD simulations of GDP-bound cryoEM structures were performed to study conformational dynamics of the respective state. a-e, Overlays of 10 randomly selected snapshots of Gαi from one representative trajectory (out of 5 total) each with 1 µs duration. The opaque model highlights the initial model used for the MD simulation, while transparent structures were obtained from subsequent frames. f-j, Overlays of 10 randomly selected snapshots of GDP binding pocket of Gαi from one representative trajectory (out of 5 total) each with 1 µs duration. The opaque model highlights the initial model used for the MD simulation, while transparent structures were obtained from subsequent frames. Backbone traces of individual frames were omitted for clarity, the shown backbone represents the starting structure after minimization. k, Violin plot showing the average center-of-mass (COM) distances of residues within Gαi nucleotide binding pocket with GDP, across all 5 simulated trajectories, highlighting a series of conformational changes across the different states. ‘Primed’ trajectory 1 and ‘unlatched’ trajectory 2 were omitted from this figure, as GDP ejects completely. i, Traces of individual MD trajectories, focusing on TM3-TM6 distances.