3D structure and stability prediction of DNA with multi-way junctions in ionic solutions

TL;DR

This study presents an improved coarse-grained model for predicting the 3D structures and stability of DNA with multi-way junctions in various ionic solutions, enhancing understanding of their biological functions.

Contribution

The paper introduces a refined electrostatic energy term and advanced sampling methods to accurately predict multi-way junction DNA structures and stability, extending beyond traditional DNA models.

Findings

Accurate prediction of DNA multi-way junction structures from sequences.

Reliable estimates of thermal stability across different ionic conditions.

Insights into unfolding pathways and stability determinants.

Abstract

Understanding the three-dimensional (3D) structure and stability of DNA is fundamental for its biological function and the design of novel drugs. In this study, we introduce an improved coarse-grained (CG) model, incorporating a more refined electrostatic energy term, the replica-exchange Monte Carlo algorithm, and the weighted histogram analysis method. The enhanced model predicts the 3D structures and stability of DNA with multi-way junctions (three-way and four-way) in various ionic environments, going beyond traditional single-stranded DNA (ssDNA) and double-stranded DNA (dsDNA). Our model demonstrates remarkable accuracy in predicting the structures of DNAs with multi-way junctions from sequences and offers reliable estimates of their thermal stability across a range of sequences and lengths, with both monovalent and divalent salts. Notably, our analysis of the thermally unfolding pathways reveals that the stability of DNA with multi-way junctions is strongly influenced by the relative stabilities of their unfolded intermediate states, providing key insights into DNA structure-function relationships.