#29 · Structural bio & protein design

Computational studies dissect GPCR activation pathways from plant GCR1 to GLP-1R

The common thread is conformational control of GPCR activation, approached through simulation and data-driven analysis of structures rather than new experimental determinations. A machine learning framework applied to experimental class A GPCR structures proposes a hybrid activation model in which ligand binding follows conformational selection, and the study also addresses G protein binding. For the plant receptor GCR1, MD and metadynamics simulations propose that abscisic acid binding closes GPA1, trapping GDP and blocking nucleotide exchange. For GLP-1R, enhanced-sampling simulations characterize how an ago-allosteric modulator stabilizes active conformations and identify two intermediate activation states. What is new is the explicit atomistic description of intermediate states and allosteric coupling to G protein signaling across receptor systems, although these results remain computational predictions.