Computational Investigation into the Inhibition of Fatal Familial Insomnia

Jacob R. Higginson
Dr. Bill R. Miller, Faculty Mentor

Fatal Familial Insomnia (FFI) is a transmissible spongiform encephalopathy, otherwise known as a prion disease. FFI is caused by a mutation in the PRNP gene which results in a point mutation within the PrP protein homodimer. FFI causes insomnia and a flattening of circadian oscillations by misfolding other proteins, reducing the cell’s ability to utilize glucose and causing cell death, primarily within the thalamocortic limbic structures of the brain. Computational analysis has been used to measure the inhibitive ability of various biomolecules on PrP’s ability to misfold proteins. Preliminary docking has been done using molecules tested in previous studies in order to establish a baseline level of protein-ligand affinity, and simulations of unbound PrP have been used to measure the overall stability of the protein. The ligand with the best binding affinity was also simulated with PrP in order to gain insight into how PrP interacts with its ligands.

Keywords: Fatal Familial Insomnia, FFI, Prion, Transmissible Spongiform Encephalopathy, Computational Analysis, PrP, PRNP

Topic(s):Biochemistry and Molecular Biology
Biology
Chemistry

Presentation Type: Oral Presentation

Session: TBA
Location: TBA
Time: TBA