Abstract: Glutathione peroxidase 4 is an enzyme encoded by the human GPX4 gene which protects cells against cell damages related to membrane lipid peroxidation and preserves mitochondrial integrity of forebrain neurons. It opens possibilities of potentially treating Alzheimer’s Disease through elevating the GPX4 protein activity. Even though studies have identified that three kinds of GPX4 mutations, including two point mutations and a double mutant, are effective in enhancing GPX4 activity and reducing progressive cognitive impairment of the human brain, the mechanism remains unknown. This research seeks to understand the relationship between GPX4 mutations and their enhanced protein activity. Various molecular dynamics techniques are employed to detect changes introduced by the mutations. In addition, the systems are examined through the lens of energetics with Thayer Lab’s newly developed heat kernel analysis method. Our data suggests that although structural analysis is an effective tool of comparing GPX4 protein systems, an energetic point of view could be adopted to better understand the mutated proteins, and even explain differences when structural changes are absent. It lends support to a novel but effective way of studying similar protein systems in the future.
Poster:
Live Poster Session:
Thursday, July 29th 1:15-2:30pm EDT