Molecular Dynamic Simulations for Mammalian Target of Rapamycin (mTOR) Variants to Characterize Potential Disruption of Porphyromonas gingivalis Induced Degradation

Abstract

Gingipains are a protease secreted by Porphyromonas gingivalis, a major cause of adult periodontitis. P. gingivalis infections are associated with suppressed adaptive immunity and increased neuroinflammation among individuals with Alzheimer’s disease. Gingipains promote neuronal damage and are associated with immunoreactivity. The mammalian target of rapamycin (mTOR) is one protein potentially influenced by gingipain function. mTOR, a protein kinase, controls rates of protein synthesis and degradation, and may also play a significant role in the Alzheimer’s phenotype. Recent evidence suggests that P. gingivalis may inhibit mTOR signaling Alzheimer’s patients. We sought to investigate the role mTOR variants may play in the interaction with gingipains and Alzheimer’s disease. The objectives were to investigate the effect mTOR variants had on structure, function and interaction with gingipains. It was hypothesized that wild type mTOR may confer gingipain induced protection from Alzheimer’s disease, while variant phenotypes may contribute to disease progression. Molecular dynamic simulations were performed to measure hydrophobic collapse and the average movement in 10ns for each structure and compared to wild type. Results suggest structural alterations among the variants which may influence interactions with gingipains. These structural changes may lend evidence to suggest subsequent in vivo analyses investigating how P. gingivalis infection may influence mTOR signaling plays in the Alzheimer’s phenotype.