Conformational Signatures of Preassembled and Active Complexes of 5-HT7 with the Gs Protein: Journal of Chemical Information and Modeling

5-Hydroxytryptamine receptor type 7 (5-HT ₇) receptor is a G protein-coupled receptor (GPCR) exhibiting noncanonical signaling properties. It has been shown that 5-HT ₇can form stable inactive preassembled complexes with its cognate G _sprotein. Structural determinants of such complex formation and the distinction between preassembled and intermediate activated complexes remain unknown. Here, we use molecular modeling and molecular dynamics simulations to determine and characterize the binding interface between this receptor and the G _sprotein in both the active and preassembly complexes. Our results show key interaction patterns specific for the different states and pinpoint unique structural features distinguishing active, inactive, and preassembled states of the receptor.