Binding of a positive allosteric modulator CDPPB to metabotropic glutamate receptor type 5 (mGluR5) probed by all-atom molecular dynamics simulations.

Positive allosteric modulators (PAMs) of metabotropic glutamate receptor type 5 (mGluR5) potentiate positive receptor response and may be effective for the treatment of schizophrenia and cognitive disorders. Although crystal structures of mGluR5 complexed with the negative allosteric modulators (NAMs) are available, no crystal structure of mGluR5 complexed with PAM has been reported to date. Thus, conformational changes associated with the binding of PAMs to mGluR5 remain elusive.

GDP Release from the Open Conformation of Gα Requires Allosteric Signaling from the Agonist-Bound Human β Adrenergic Receptor.

G-protein-coupled receptors (GPCRs) transmit signals into the cell in response to ligand binding at its extracellular domain, which is characterized by the coupling of agonist-induced receptor conformational change to guanine nucleotide (GDP) exchange with guanosine triphosphate on a heterotrimeric (αβγ) guanine nucleotide-binding protein (G-protein), leading to the activation of the G-protein. The signal transduction mechanisms have been widely researched and . However, coordinated communication from stimulating ligands to the bound GDP still remains elusive.