# In Silico Drug Design Targeting RNA Repeat Expansions

> **NIH NIH R15** · FLORIDA ATLANTIC UNIVERSITY · 2023 · $90,396

## 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:** 10796593
- **Project number:** 3R15GM146199-01S1
- **Recipient organization:** FLORIDA ATLANTIC UNIVERSITY
- **Principal Investigator:** Ilyas Yildirim
- **Activity code:** R15 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $90,396
- **Award type:** 3
- **Project period:** 2022-04-01 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10796593

## Citation

> US National Institutes of Health, RePORTER application 10796593, In Silico Drug Design Targeting RNA Repeat Expansions (3R15GM146199-01S1). Retrieved via AI Analytics 2026-05-31 from https://api.ai-analytics.org/grant/nih/10796593. Licensed CC0.

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