Celebration of Scholars
P47 - An Analysis of Molecular Dynamics Simulations of a Natural Product Binding to the V122I Transthyretin Variant
Name:
Ingrid Cerna
Major: Biology
Hometown: Waukegan
Faculty Sponsor: Kevin Morris
Other Sponsors:
Type of research: Independent research
Abstract
Transthyretin or TTR is a protein that transports hormones in the bloodstream. Genetic mutations in the TTR gene can lead to misfolded proteins that aggregate into fibrils causing diseases like Amyloid cardiomyopathy or FAC. In this genetic disorder, these amyloid fibrils aggregate into plaques around the heart tissue, interfering with its function. Some mutations of TTR , such as Valine-122 to Isoleucine or V122I decreases the stability of the tetramer and increases the chances of the TTR protein dissociating and aggregating into plaques. Resveratrol is a molecule that binds to TTR and stabilizes the tetramer protein. Therefore, resveratrol and molecules with similar structures are potential drug treatments for FAC diseases. Resveratrol has other health benefits as well, such as being an antioxidant, antidiabetic, and antineoplastic. Resveratrol can be found in foods such as grapes, berries, peanuts, pistachios and dark chocolate. The purpose of this research was to use molecular dynamics simulations to investigate how resveratrol stabilizes the TTR protein. The molecular dynamics simulation results showed that resveratrol inserted into the TTR binding pocket by forming hydrogen bonds with the receptor’s Serine-117 residues. Inside the pocket resveratrol also experienced hydrophobic interactions with TTR Leucine-110 residues. Finally, a resveratrol derivative that contained an anionic carboxylate group interacted more strongly with TTR than the neutral resveratrol molecule.Submit date: March 6, 2025, 1:43 p.m.