Fig. 2. Workflow for extracting the spatiotemporal heat map for the residue contacts in GPCR:G protein interface.

a We used six crystal and cryo-EM structures of GPCR:G protein complexes to model the interactions of two Gs-coupled, two Gi-coupled, and two Gq-coupled GPCR:G protein pairs. Atomistic MD simulations were performed as five replicates, each replicate extended to >800 ns of simulation time for each of these GPCR:G protein complexes. The last 200 ns window of each replicate was combined into a 1 μs ensemble trajectory used for further analysis. Source data are hosted at GPCRmd.org. b The sidechain-to-sidechain intermolecular contacts between GPCR and Gα proteins were computed for each of the six complexes using the get_contacts.py method. We obtained 764 contacts for analysis and identified “persistent contacts” as those sampled for >20% frequency in one or both systems representing each class (Gs, Gi, Gq). Among these persistent contacts, we identified a subset that appear uniquely in interactions of one Gα protein family (“specific contacts”) and those which are found across all of the Gα protein subfamilies (Gs, Gi, and Gq; “common contacts”).