Table 3.

A summary of MD simulation studies on GPCR-G protein interactions.

System	Method	Major findings	Reference
β2AR-GαCT	MD	Interactions between the β2AR and GαCT are ligand dependent.	(Goetz et al., 2011)
β2AR-Gs	MD	Nanobody plays an important role in stabilizing the β2AR-Gs complex.	(Feng et al., 2012)
β2AR-Gs	MD	Binding of different ligands affects stability of the β2AR-Gs complex.	(Bai et al., 2013)
β2AR-Gs D2R-Gi	MD	Receptor ICL3 and the α5-helix of Gα play an important role in GPCR-G protein coupling.	(Kling et al., 2013)
CB1-Gi	MD, Ala mutation	The Gα α5 helix of the G protein plays an important role in the CB1-Gi coupling.	(Shim et al., 2013)
CB2-Gi	MD, cross-linking	The ICL2 in CB2 and the Gα α5 helix of the G protein play an important role in the CB2-Gi coupling.	(Mnpotra et al., 2014)
β2AR-Gi/Gs	MD	The TM6 helix in the β2AR plays an important role in binding selectivity of Gi and Gs proteins.	(Rose et al., 2014)
β2AR-Gs	MD, DEER spectroscopy	Separation of the Ras and helical domain of the Gα subunit is necessary but not sufficient for rapid nucleotide release.	(Dror et al., 2015)
β2AR-Gs	Kino-Geometric Sampling	Interaction between the αN helix of the G protein and the receptor ICL2 is important for nucleotide release.	(Pachov, Fonseca, Arnol, Bernauer, & van den Bedem, 2016)
M2-nanobody	GaMD	Nanobody is important in stabilizing the active conformational state of the M2 receptor.	(Miao & McCammon, 2016b)
β2AR-Gs M2R-nanobody μOR-Gs/nanobody	Metadynamic	The binding of intracellular binding partners alters agonist binding modes.	(Saleh, Ibrahim, & Clark, 2017)
β2AR-Gs β2AR-arrestin	Metadynamics	The structure and dynamics of GPCR-G protein complexes depend strongly on the nature of small-molecule ligands.	(Saleh, Saladino, et al., 2017)
Rhodopsin–Gi	MD, DEER	A model of rhodopsin-Gi is presented.	(Van Eps et al., 2018)
M2-nanobody	GaMD	GaMD captured spontaneously binding the G protein mimic nanobody to a muscarinic GPCR.	(Miao & McCammon, 2018)
Rhodopsin-arrestin	MD, Fluorescence spectroscopy	GPCRs could stimulate arrestin through interactions mediated by the receptor phosphorylated cytoplasmic tail (RP tail) only, the receptor core only, or both the receptor core and RP tail.	(Latorraca et al., 2018)