Probing Self-Assembly of G Protein-Coupled Receptor Oligomers in Membranes Using Molecular Dynamics Modeling and Experimental Approaches

G protein-coupled receptors (GPCRs) transduce chemical signals across membranes and mediate many fundamental cellular signaling pathways. The “signalosome” is the basic signaling unit and comprises and an agonist ligand-receptor complex bound to a heterotrimeric guanine nucleotide-binding regulatory protein (G protein) in a biological membrane. Although in many cases, a monomeric GPCR is competent to transduce signals, the role of receptor dimerization and higher-order self-assembly and how receptor oligomers affect pharmacology and cellular physiology has emerged as one of the most intriguing and challenging problems in the field. Here we review recent insights gained from a multidisciplinary research approach using computational coarse grain molecular dynamics (CGMD) simulations and experiments facilitated by molecular and chemical biology approaches. One particular focus of recent work has been to define the contact sites between receptor dimers.