# New computational tools for predicting ion effects in RNA structures

> **NIH NIH R01** · UNIVERSITY OF MISSOURI-COLUMBIA · 2020 · $309,161

## Abstract

Project Summary
 The current computational tools cannot keep up the pace with steadily emerging RNA sequences and new
functions such as riboswitch-mediated regulation of gene expression in bacteria, RNA-guided genome engineer-
ing (CRISPR), and RNA-based drug design and delivery. One of the unsolved key issues is the prediction and
understanding of the role of metal ions in RNA structure formation. The problem is critically important for RNA
functions because RNAs are highly charged; thus, without the participation of the metal ions in the solution, RNAs
simply won't fold. Furthermore, there is increasing support for the idea that metal ions in the cellular environment
can play a significant role in the regulation of gene expression by causing RNA structure changes. The biological
importance of ion effects underscores the urgent request for computational tools for accurate prediction of the
ion effects.
 The objective of this project is to develop successful computational tools, including models, software pack-
ages, and web servers to predict and understand the role of metal ions in RNA structures and functions. By
including the correlation and fluctuation effects for metal ions, considerable progress has been made for the ion
effects in small and simple RNA structures. However, accurate prediction for the ion (especially Mg2+) effects
has not been possible for large, biologically important RNAs. We now propose to develop computational tools
that can provide such accurate predictions. Our goals are (a) to develop and validate a novel sampling algorithm
that enables predictions of the ion effects for large RNA structures, (b) to develop and validate a new model
for predicting metal ion binding sites in RNA, (c) through collaboration with RNA structural biology laboratory to
develop an ion effect model for flexible RNA structures, and (d) to convert the computational models into user
friendly, freely accessible, open-source software package and web servers.
 The proposed new algorithms will be directly applied to important problems related to human diseases such
as the structure and stability of Hepatitis C virus genome RNA. Furthermore, the ability to predict the metal
ion effects will allow us not only to understand the formation of RNA functional structures but also to design
therapeutic strategies by weakening or strengthening ion binding and consequently changing the structures and
stabilities of human disease-related RNAs.

## Key facts

- **NIH application ID:** 9857025
- **Project number:** 5R01GM117059-04
- **Recipient organization:** UNIVERSITY OF MISSOURI-COLUMBIA
- **Principal Investigator:** SHI-JIE CHEN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $309,161
- **Award type:** 5
- **Project period:** 2017-02-01 → 2022-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9857025

## Citation

> US National Institutes of Health, RePORTER application 9857025, New computational tools for predicting ion effects in RNA structures (5R01GM117059-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9857025. Licensed CC0.

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