# Molecular Dynamics Simulations of RNA Stem-Loop Folding Using an Atomistic Force Field and a Generalized Born Implicit Solvent

## TL;DR

This paper uses molecular dynamics simulations to successfully model RNA stem-loop folding, achieving high accuracy for stem regions but facing challenges with loop structures.

## Contribution

The study demonstrates successful de novo folding of RNA stem-loops using an atomistic force field and implicit solvent model, achieving RMSD values under 2 Å for stem regions.

## Key findings

- 18 stem-loops without bulges or internal loops were folded with RMSD <2 Å for stem regions.
- Five of eight stem-loops with bulges or internal loops retained native base pairs in stem regions.
- Loop regions showed RMSD of ~4 Å, indicating challenges in modeling these areas accurately.

## Abstract

Accurate modeling
of the structural dynamics of ribonucleic acid
(RNA) molecules, including common stem-loop motifs, remains challenging.
This study presents de novo folding simulations of
a diverse set of 26 RNA stem-loops, ranging from 10 to 36 residues,
with and without bulges or internal loops, starting from their extended
conformations. These simulations employed conventional molecular dynamics
using an atomistic force field extensively refined by the Shaw group
(

TanD.,

Proc. Natl. Acad. Sci. U.S.A.
2018, 115, E1346−E1355, 10.1073/pnas.1713027115
29378935
PMC5816156) and an implicit solvent
model developed by the Simmerling group (

NguyenH.,

J. Chem. Theory Comput.
2015, 11, 3714−3728, 10.1021/acs.jctc.5b00271
26574454
PMC4805114). The 18 stem-loops without bulges or internal loops
were folded into their respective structures, retaining all native
base pairs in the stem regions. For most of these models, root mean
square deviation (RMSD) values relative to experimentally determined
structures were <2 Å for stem regions and <5 Å for
the molecules. Furthermore, five of the eight stem-loops containing
bulges or internal loops were successfully folded into structures
with all respective native base pairs in the stem regions. The models
initially formed stems directly connected to hairpin loops, followed
by the remaining duplex stems between the bulge or internal loop and
the terminal. The RMSD values for these structures were 0.9–4.5
Å for the stem regions and 2.8–8.3 Å for the molecules.
The RMSD values for the loop regions were approximately 4 Å for
all models. Accurate modeling of loop structures remains challenging
in simulations using the implicit solvent model. However, our success
in recapitulating the RNA stem folding of fundamental stem-loop motifs
represents a pivotal step toward enhancing reliable and accurate modeling
of RNA structural dynamics.