Date of Award

2023

Document Type

Dissertation/Thesis

Submission Date

October 2026

Thesis/Dissertation Advisor [Chair]

Yildirim, Ilyas

Abstract

Alzheimer’s Disease (AD) is a neurodegenerative disease that affects memory with no known cure. One of the mechanisms behind AD is an overproduction of imbalanced tau proteins caused by a mutation in the microtubule-associated protein tau (MAPT) mRNA, which has an RNA adenosine bulge (A-bulge). Targeting the A-bulge motif in the MAPT can stabilize the junction site and balance the imbalanced tau isoforms produced. Being able to stabilize the A-bulge site can lead to finding therapeutics for combating AD. Past research of structures discovered three unique compounds that stabilize the A-bulge site (Figure 1). We investigated the binding properties of these three compounds and their stabilities using molecular dynamics (MD) simulations. We hypothesize that the three compounds can be optimized to enhance their binding affinities to the RNA A-bulge site, which would lead to quicker and inexpensive ways to optimize drugs for patient treatments. Preliminary results showed that the bound states match partially well with the MD predictions. Our future studies will involve optimization of these three compounds using dynamic binding methodology to discover novel drugs having potent binding affinities and specificities.

Comments

Thesis (B.S.)--Florida Atlantic University, Harriet L. Wilkes Honors College, 2023

Extent

26 p.

Identifier

FAUHT00277

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