Predicting 3D structure and stability of RNA pseudoknots in monovalent and divalent ion solutions

TL;DR

This study uses a coarse-grained model to accurately predict the 3D structures and stability of RNA pseudoknots in various ion solutions, providing insights into their unfolding pathways and dependence on sequence and ion conditions.

Contribution

The paper introduces a validated coarse-grained model capable of predicting RNA pseudoknot structures and stability across different ion concentrations, advancing understanding of their folding and unfolding mechanisms.

Findings

Model successfully predicts RNA pseudoknot structures from sequences.

Stability predictions are reliable across a range of ion concentrations.

Unfolding pathways depend on stability of intermediate states and are influenced by sequence and ion conditions.

Abstract

RNA pseudoknots are a kind of minimal RNA tertiary structural motifs, and their three-dimensional (3D) structures and stability play essential roles in a variety of biological functions. Therefore, to predict 3D structures and stability of RNA pseudoknots is essential for understanding their functions. In the work, we employed our previously developed coarse-grained model with implicit salt to make extensive predictions and comprehensive analyses on the 3D structures and stability for RNA pseudoknots in monovalent/divalent ion solutions. The comparisons with available experimental data show that our model can successfully predict the 3D structures of RNA pseudoknots from their sequences, and can also make reliable predictions for the stability of RNA pseudoknots with different lengths and sequences over a wide range of monovalent/divalent ion concentrations. Furthermore, we made comprehensive analyses on the unfolding pathway for various RNA pseudoknots in ion solutions. Our analyses for extensive pseudokonts and the wide range of monovalent/divalent ion concentrations verify that the unfolding pathway of RNA pseudoknots is mainly dependent on the relative stability of unfolded intermediate states, and show that the unfolding pathway of RNA pseudoknots can be significantly modulated by their sequences and solution ion conditions.