Abstract
Many cells express certain proteins called prion proteins. It is known that prion proteins are involved in copper binding but their exact function is still uncertain. If a specific misfolding of these proteins happens, prions are created. Prions are able to induce misfolding. which allows them to propagate the condition. If a misfolding cascade forms into an aggregate, it can cause a neurodegenerative disorder. As a group, these diseases are known as transmissible spongiform encephalopathies (TSEs). The AGAAAGA sequence was specifically identified as an inhibitor that binds to the monomer prior to conversion. We sought to determine what specific region of the prion protein is most conducive to AGAAAAGA peptide binding. Three initial peptide conformations were tested, generated by the Robetta server. Then, docking calculations were performed on recombinant Syrian hamster prion protein using the free software Autodock 4.2 to identify binding modes. We then processed the data using a more refined free energy method. We found that the second and third a-helices play an important role in "tying" these helices together. We also found that the ligand does not bind to the homologous sequence.