Insights from molecular dynamics simulations to exploit new trends for the development of improved opioid drugs

Neurosci Lett. 2019 May 1;700:50-55. doi: 10.1016/j.neulet.2018.02.037. Epub 2018 Feb 18.


Having accidental deaths from opioid overdoses almost quadrupled over the past fifteen years, there is a strong need to develop new, non-addictive medications for chronic pain to stop one of the deadliest epidemics in American history. Given their potentially fewer on-target overdosing risks and other adverse effects compared to classical opioid drugs, attention has recently shifted to opioid allosteric modulators and G protein-biased opioid agonists as likely drug candidates to prevent and/or reverse opioid overdoses. Understanding how these molecules bind and activate their receptors at an atomistic level is key to developing them into effective new therapeutics, and molecular dynamics-based strategies are contributing tremendously to this understanding.

Keywords: Allosteric modulator; Biased agonism; Functional selectivity; Receptor; Structure.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Allosteric Regulation
  • Analgesics, Opioid / adverse effects
  • Analgesics, Opioid / chemistry*
  • Analgesics, Opioid / toxicity
  • Animals
  • Drug Overdose / drug therapy
  • Drug Overdose / prevention & control
  • Humans
  • Molecular Dynamics Simulation*
  • Narcotic Antagonists / chemistry
  • Protein Binding
  • Protein Conformation
  • Receptors, Opioid / agonists
  • Receptors, Opioid / chemistry


  • Analgesics, Opioid
  • Narcotic Antagonists
  • Receptors, Opioid