August 28, 2014, 11:30 am, 315 Stinson Remick
Advisor: Dr. Jesus Izaguirre
Dr. Mary Ann McDowell Dr. Christopher Sweet Dr. Aaron Striegel
Characterization of the Anopheles gambiae Octopamine Receptor and Discovery of Potential Agonists and Antagonists Using a Combined Computational-Experimental Approach
Octopamine receptors (OARs) perform key operations in the biological pathways of invertebrates only, making this class of G-Protein Coupled Receptors (GPCRs) a potentially good target for insecticides. However, the lack of structural and experimental data for this insect-essential GPCR class has promoted the development of homology models that are good representations of their biological equivalents and will thus be useful in the development of an insecticide. We report here the functional characterization of two Anopheles gambiae OARs and the discovery of new OAR agonists and antagonists based on virtual screening and Molecular Dynamics (MD) simulations. Experimental validation of the results shows the accuracy of our model. Supporting prior GPCR studies, Asp100 in the TM3 region, and Ser206 and Ser210 in the TM5 region were found to be important to the activation of the protein. The current combined computational and experimental approach seems appropriate for creating and refining homology models of the octopamine receptor and in turn aid in the discovery of new and effective insecticides.