Insights From Molecular Dynamics Simulations of a Number of G-Protein Coupled Receptor Targets for the Treatment of Pain and Opioid Use Disorders.

Effective treatments for pain management remain elusive due to the dangerous side-effects of current gold-standard opioid analgesics, including the respiratory depression that has led to skyrocketing death rates from opioid overdoses over the past decade. In an attempt to address the horrific opioid crisis worldwide, the National Institute on Drug Abuse has recently proposed boosting research on specific pharmacological mechanisms mediated by a number of G protein-coupled receptors (GPCRs). This research is expected to expedite the discovery of medications for opioid overdose and opioid use disorders, leading toward a safer and more effective treatment of pain. Here, we review mechanistic insights from recent all-atom molecular dynamics simulations of a specific subset of GPCRs for which high-resolution experimental structures are available, including opioid, cannabinoid, orexin, metabotropic glutamate, and dopamine receptor subtypes.