# Structure-based Simulation of Riboswitches: Electrostatic Effects

> **NIH NIH R01** · TRIAD NATIONAL SECURITY, LLC · 2022 · $308,649

## Abstract

Abstract
With new developments in RNA biology, RNA biotechnology and RNA biomedicine each year, there
is an urgent need to understand RNA mechanism in as much detail as possible. Small RNA
techniques (miRNAs and siRNAs), and CRISPR-Cas9 gene editing are changing the landscape of
biotechnology and biomedicine. Riboswitch RNAs are (i) important in bacterial gene regulation, (ii)
interesting antimicrobial targets, and (iii) have potential for optimizing biotechnologies such as
CRISPR-Cas9. These RNAs are excellent model systems for studying the hallmarks of RNA
mechanism: magnesium-driven electrostatic effects, large 3-D conformational changes, changes in
secondary structure, and co-transcriptional effects. Since 2009, we have published a variety of
explicit solvent molecular dynamics simulation, structure-based molecular simulation, and wetlab
biochemistry studies of riboswitches to understand their operation and the effect of magnesium on
riboswitch structure and function. Focusing mainly on the aptamer domain of the SAM-I riboswitch,
we have established that magnesium and SAM work together to achieve the fully collapsed, native
state. In addition, magnesium facilitates a partial collapse, leaving the aptamer in a state permissible
to strand invasion by the expression platform. In this project, we will study the entire riboswitch
(aptamer and expression platform), investigating the role of magnesium in riboswitch function. Using
atomistic structure-based electrostatic potential models for RNA and magnesium, we will disentangle
the roles of inner sphere, outer sphere and diffuse magnesium ion effects in riboswitch operation.
Using experimentally determined intermediate configurations, we will study transitions between
intermediates during various points of riboswitch function. Our modeling we be enhanced by
constraints from a variety of biochemical and biophysical experiments. We will address the
fundamental question: How does the ionic environment enable riboswitch RNAs to accomplish their
function?

## Key facts

- **NIH application ID:** 10398108
- **Project number:** 5R01GM110310-07
- **Recipient organization:** TRIAD NATIONAL SECURITY, LLC
- **Principal Investigator:** Karissa Y Sanbonmatsu
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $308,649
- **Award type:** 5
- **Project period:** 2015-03-15 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10398108

## Citation

> US National Institutes of Health, RePORTER application 10398108, Structure-based Simulation of Riboswitches: Electrostatic Effects (5R01GM110310-07). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10398108. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*