Schizophrenia is a severe brain disorder that usually produces a lifetime of disability. Related research shows activating metabotropic glutamate receptors holds therapeutic potential. Agonist-positive allosteric modulations (ago-PAMs) not only activate metabotropic glutamate receptors but also enhance glutamate-induced responses, offering a promising treatment strategy. However, the molecular mechanisms by which ago-PAM enhances glutamate-induced responses remain unclear, as does the potential influence of glutamate on ago-PAM. In this study, Gaussian accelerated molecular dynamics and tau random acceleration molecular dynamics simulations were employed to investigate the molecular mechanism between ago-PAM and glutamate in full-length mGlu