Ions Everywhere? Mg²⁺ in the μ-Opioid GPCR and Atomic Details of Their Impact on Function

Filizola and co-workers have applied a combination of long-time molecular dynamics and oscillating chemical potential grand canonical Monte Carlo/molecular dynamics to investigate the distribution of Mg²⁺ and Na⁺ in the μ-opioid receptor and their impact on its function. Results indicate atomic details of potential mechanisms by which Mg²⁺ leads to increased efficacy of opioid analgesics. The presence of information flow between the extracellular loops and the intracellular region of the G-protein-coupled receptors that interacts with G-proteins in the presence of Mg²⁺ may be a phenomenon occurring in other G-protein-coupled receptors and, therefore, potentially of broad impact.