A Coarse-Grained Model for Predicting RNA Folding Thermodynamics

TL;DR

This paper introduces a coarse-grained thermodynamic model for RNA folding that accurately predicts stability across various structures and conditions by incorporating stacking, hydrogen bonding, and electrostatic interactions.

Contribution

The model uniquely combines nucleotide-specific stacking parameters with implicit ion modeling, calibrated against experimental data for multiple RNA structures.

Findings

Single parameter set fits thermodynamic data for three RNA molecules.

Model predicts RNA folding thermodynamics across temperature and salt ranges.

Counterion condensation reduces backbone charge to 60% at 37°C.

Abstract

We present a thermodynamically robust coarse-grained model to simulate folding of RNA in monovalent salt solutions. The model includes stacking, hydrogen bond and electrostatic interactions as fundamental components in describing the stability of RNA structures. The stacking interactions are parametrized using a set of nucleotide-specific parameters, which were calibrated against the thermodynamic measurements for single-base stacks and base-pair stacks. All hydrogen bonds are assumed to have the same strength, regardless of their context in the RNA structure. The ionic buffer is modeled implicitly, using the concept of counterion condensation and the Debye-H\"uckel theory. The three adjustable parameters in the model were determined by fitting the experimental data for two RNA hairpins and a pseudoknot. A single set of parameters provides good agreement with thermodynamic data for the three RNA molecules over a wide range of temperatures and salt concentrations. In the process of calibrating the model, we establish the extent of counterion condensation onto the single-stranded RNA backbone. The reduced backbone charge is independent of the ionic strength and is 60% of the RNA bare charge at 37 degrees Celsius. Our model can be used to predict the folding thermodynamics for any RNA molecule in the presence of monovalent ions.