Understanding the Molecular Mechanisms That Govern Opioid Potency Through a Course-embedded Computational Research Project

In recent decades awareness surrounding the class of drugs known as opioids has risen due to what many have termed the “opioid epidemic.” Rates in opioid-related drug overdoses have spiked due to increased opioid addiction and the illegal lacing of illicit drugs, such as marijuana, with opioid compounds like fentanyl, increasing their potency. Coexisting with the devastating realities of overdose and addiction, however, is the clinical demand for these drugs and their potency to manage extreme pain. Herein, we describe the results of a course-embedded computational research project to understand the factors responsible for opioid potency. In the present study, the chemical properties of commonly used opioids and their interactions with receptors are investigated using computational techniques. In particular, the molecular basis for the high potency of fentanyl is investigated. The drug molecules were constructed using a web-based tool, WebMO. The electronegativity and chemical hardness of nine opioids and one pain reliever were determined using a quantum chemistry software package named Q-Chem. The binding interactions between the same set of opioid molecules and their receptors were studied using AutoDock FR, interactions within the receptor’s binding pocket were analyzed using Visual Molecular Dynamics (VMD), and SwissADME was used to investigate the pharmacokinetic properties of each drug molecule.