Abstract
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.