Computational Molecular Docking of Fluorinated Morphine Derivatives for Improved Pain Management

Authors

Mirabella Romano, Chapman UniversityFollow
Emily Chen, Chapman UniversityFollow

Document Type

Poster

Publication Date

Winter 12-3-2025

Faculty Advisor(s)

Dr. Matthew Gartner

Abstract

The opioid epidemic impacts 60 million people worldwide every year. Morphine, a commonly prescribed opioid, binds to the μ-opioid receptor (MOR) in the body via protonation of its tertiary amino group and the MOR. An unfortunate side effect of this binding process is its non-selectivity in both peripheral and central tissues. While activation within inflamed peripheral tissues results in pain relief, activation within central tissues results in the unwanted and addictive side effects of opioids. Because there is a discrepancy in pH between healthy (central) and inflamed (peripheral) tissue, selective binding within the inflamed tissues could provide pain relief without addictive properties. Fluorination of the morphine molecule reduces its pKa, promoting selective protonation and receptor binding in the lower pH environment of inflamed tissues while avoiding activation within the CNS. Additionally, removal of the C and D rings alters steric properties, improving receptor fit and binding efficiency by increasing molecular flexibility. The aim of this study is to further assess these derivatives using molecular docking simulations conducted in Rowan, a graphical interface for AutoDock Vina that allows visualization and evaluation of ligand-receptor interactions. Docking simulations were performed using a manually defined binding pocket. Specific ligands modeled included protonated models of morphine, morphine BC1, morphine BC2, and morphine BC3 derivatives. Out of the different ligands, protonated models of morphine BC2 and BC3 demonstrated the best docking affinity with the least ligand strain. These docking results provide critical groundwork for selecting derivatives with optimal receptor complementarity to guide future synthesis of non-addictive opioid analogs.

Comments

Presented at the Fall 2025 Student Scholar Symposium at Chapman University.

Recommended Citation

Romano, Mirabella and Chen, Emily, "Computational Molecular Docking of Fluorinated Morphine Derivatives for Improved Pain Management" (2025). Student Scholar Symposium Abstracts and Posters. 773.
https://digitalcommons.chapman.edu/cusrd_abstracts/773