Date Approved


Embargo Period


Document Type


Degree Name

M.S. Pharmaceutical Sciences


Chemistry & Biochemistry


College of Science & Mathematics


Chun Wu, Ph.D.

Committee Member 1

Gregory A. Caputo, Ph.D.

Committee Member 2

Thomas M. Keck, Ph.D.


Delta Opioid Receptor


Opioids--Receptors; Drug development


Medicinal Chemistry and Pharmaceutics


The DOR is the least studied out of the three opioid receptors (Mu, Kappa, and Delta). The most is known of the Mu Opioid receptor (MOR) and the drugs that target it have led to the global opioid epidemic due to their adverse effects of tolerance and addiction. The DOR is not known for the same adverse effects and therefore, is a promising pharmacological target for the development of new opioid ligands. In this thesis, molecular modeling, simulations and other computational methods are introduced in Chapter 1 where these methods are used to study the activation mechanism of DOR (Chapter 2) and are used to identify novel DOR agonists (Chapter 3). Recently, both the inactive and active conformations of the DOR have been solved. However, the activation mechanism remains to be elusive. In Chapter 2, molecular dynamics (MD) simulations will offer a deeper insight into the dynamics and interactions beginning with the inactive conformation of the receptor when bound to an agonist undergoing a conformational change. Chapter 3 will involve the use of high-throughput screening of new molecules for potential agonist candidates using multiple conformations of the active conformation of the DOR. The top lead compounds subjected further computational analysis on their drug properties to ensure that they do not cause any unwanted side effects. Final lead compounds are available for experimental testing.