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Rufaida M. Al Zoubi

Posted on February 28, 2018


Date - February 28, 2018
1:00 pm - 2:00 pm


Ph.D. Dissertation Seminar – 752
Title: “Molecular Level Studies on The Cannabinoid Receptor Type 1 (CB1): Biased Signaling and MD Simulations”
Advisor: Dr. Patricia H. Reggio


Molecular Level Studies on The Cannabinoid Receptor Type 1 (CB1): Biased Signaling and MD Simulations

The CB1 receptor is a class A G-protein coupled receptor (GPCR), and is the most abundant neuro-modulatory receptor in the CNS. With its location at presynaptic termini, it regulates the function of other receptors, including the dopamine, serotonin, GABA, opioid and glutamate receptors. Many potential therapeutic applications targeting the CB1 receptor are under investigation. However, the unformed knowledge in drug-receptor interactions at the molecular level, and in the CB1 receptor signaling properties, has hampered the transition of many synthesized CB1 receptor agonists and antagonists to clinical use. Three studies will be presented; in the first study, biased signaling through class A GPCRs in general and through the CB1 receptor specifically will be discussed, and a set of hypothesis-driven mutations on the CB1 receptor that yielded a CB1 receptor that exhibits biased signaling through the β-arrestin pathway will be presented. The second study applied molecular dynamics simulations to investigate the docking of a CB1 receptor antagonist (5-(4-chlorophenyl)-N-[(1R,2R)-2-hydroxycyclohexyl]-6-(2- methoxyethoxy)-3-pyridinecarboxamide (14h)) inside the CB1 receptor. Results from the docking study will help in the remodeling of the CB1 receptor N-terminus. Finally, parameterization and MD simulation of the biarylpyrazole inverse agonist (SR-141716A) will be presented. Results from these studies will aid the development of new ligands that target the CB1 receptor.