# In Silico Drug Design Targeting RNA Repeat Expansions

> **NIH NIH R15** · FLORIDA ATLANTIC UNIVERSITY · 2022 · $419,485

## Abstract

Project Summary.
 RNA orchestrates how critical biological functions are controlled, including catalysis, gene
expression, enzymatic activities, and protein folding. Misregulation of gene expression cause dysregulation of
RNA, which cause many heritable diseases such as Myotonic Dystrophy, Huntington's disease, and Fragile
X Syndrome caused by RNA transcripts that contain expanded repeats. The proposal seeks to create unique
computational tools to investigate interaction of small molecules and ligands with dynamic RNA loops and
to optimize lead compounds targeting RNA repeat expansions via inclusion of functional groups.
Results will be used to facilitate drug design targeting RNA.
 Through a series of pilot studies, I have demonstrated how a more precise RNA force field improves
the predictions. The objective of this proposal is to utilize this state-of-art RNA force field jointly with
ever-increasing computational power to provide unique solutions in RNA-targeting pharmacotherapies. In
Aim 1, a physics-based novel method will be created to predict the binding properties of small molecules
targeting dynamic RNA loops. In Aim 2, I propose to develop a computational tool to optimize the binding
properties of small molecules targeting RNA repeats via inclusion of functional groups. In Aim 3, design
principles of artificial ligands targeting RNA repeats will be discovered using computational methods.
 This project will dramatically expand our understanding on how RNA loops fold and interact with
small molecules and ligands. It will also have broader and potentially therapeutic implications for
understanding RNA molecule interaction with other types of proteins such as the RNA-induced silencing
complex, nucleic acid chaperones, and RNP complexes. This proposal takes advantage of a collaboration
with Scripps Research Institute (Jupiter, FL). Furthermore, the research environment will provide numerous
opportunities for career development of undergraduate and graduate students through national research
presentations, collaborations, and training in the responsible conduct of research.

## Key facts

- **NIH application ID:** 10439166
- **Project number:** 1R15GM146199-01
- **Recipient organization:** FLORIDA ATLANTIC UNIVERSITY
- **Principal Investigator:** Ilyas Yildirim
- **Activity code:** R15 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $419,485
- **Award type:** 1
- **Project period:** 2022-04-01 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10439166

## Citation

> US National Institutes of Health, RePORTER application 10439166, In Silico Drug Design Targeting RNA Repeat Expansions (1R15GM146199-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10439166. Licensed CC0.

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