Structural biology studies reveal the importance of protein dynamics on understanding molecular mechanisms underlying allosteric modulation of G protein-coupled receptors (GPCR) that offer insights into future GPCR research and drug discovery.

Functional analysis reveals a distinct mode of action of the allosteric modulators in the GABA_B receptor in a pocket that is formed only in the active state and identifies a region in the GABA_B2 subunit important for allosteric agonism.

Single molecule subunit counting, FRET and electrophysiology experiments reveal that metabotropic glutamate receptor subunits interact and rearrange at the level of the transmembrane domains in response to allosteric modulators.

Opioid drug efficacy and allosteric modulation is measured using an active state sensor of the mu-opioid receptor.

Ligands with different efficacy profiles shift the free energy landscape of the beta2 adrenergic receptor activation and stabilize diverse active-like states via the switch of microswitches lining an allosteric pathway.

A series of novel compounds selective for N-methyl-D-aspartate-type glutamate receptor includes positive and negative allosteric modulators that act at the same site, show use-dependence, increase agonist potency, and have differential activity based on the agonist concentration.

Generation of a highly deuterated 13C-methyl labeled wild-type GPCR sample is used to facilitate characterization of the molecular environments and fast ps-ns dynamics of sidechains when the receptor is bound to ligands of different efficacy.

Chemically distinct opioid ligands promote selective protein recruitment by opioid receptors in intact cells.

Transcriptional activation of the orphan nuclear receptor Nurr1 by ligands targeting its heterodimer partner retinoid X receptor alpha (RXRα) occurs through a nonclassical pharmacological mechanism involving ligand-binding domain protein-protein interaction inhibition.

Contrary to previous findings, class A GPCRs share a common activation pathway that directly links ligand binding to G-protein activation, as revealed by novel quantitative analysis.