Melting Profile of DNA in Crowded Solution: Model-Based Study

TL;DR

This study explores how macromolecular crowding affects DNA melting, showing that crowders stabilize DNA, especially in short sequences.

Contribution

The novel contribution is the model-based investigation of crowder effects on DNA melting in crowded environments.

Findings

Crowders stabilize double-stranded DNA (dsDNA), particularly in short DNA duplexes.

The effect of crowders on DNA melting is more pronounced in short DNA sequences.

Findings align with in vitro observations and enhance understanding of DNA in cell-like environments.

Abstract

Recent advances in molecular dynamics (MD) simulations and the introduction of artificial intelligence (AI) have resulted in a significant increase in accuracy for structure prediction. However, the cell is a highly crowded environment consisting of various macromolecules, such as proteins and nucleic acids. The macromolecular crowding and solution conditions, such as temperature, ion concentration, and the presence of crowders, significantly influence the molecular interactions between and structural changes in proteins and nucleic acids. In this study, we investigate the presence of crowders and their effect on the melting of DNA molecules by analyzing melting profiles of short and long heterogeneous DNA duplexes. In particular, we examine how multiple inert crowders, randomly distributed along long DNA chains, influence DNA melting. We find that the presence of crowders stabilizes double-stranded DNA (dsDNA), with this effect being more pronounced in short DNA duplexes. These findings complement in vitro observations and improve our understanding of dsDNA in cell-like environments.

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