Role of bubble positioning in force induced melting of DNA

TL;DR

This study explores how the position of bubbles within DNA influences its melting behavior under force, using simulations and models to reveal the importance of sequence arrangement and entropy effects.

Contribution

It introduces a comparative analysis of bubble positioning effects on DNA melting using Brownian Dynamics and Gaussian Network Models, highlighting the role of entropy.

Findings

Melting initiates after stretching ~9 GC base-pairs at high force in simulations.

Sequence arrangement affects DNA stability and melting behavior.

Entropy significantly influences the force-temperature phase diagram.

Abstract

We investigate the role of bubble positioning in the force-induced melting of double-stranded DNA using two distinct approaches: Brownian Dynamics simulations and the Gaussian Network Model. We isolate the effect of bubble positioning by using DNA molecules with 50% AT - 50% GC base-pair composition which ensures constant enthalpy. Our results reveal that it is not just the sequence itself, but its specific arrangement that influences DNA stability. We examine two types of DNA sequences containing a block of either AT or GC base-pairs, resulting in the formation of a large bubble or a smaller bubble within the DNA, respectively. By systematically shifting these blocks along the strand, we investigate how their positioning influences the force-temperature phase diagram of DNA. Our Brownian dynamics simulations reveal that, at high forces, melting of the entire DNA strand is initiated after stretching $\approx 9$ GC base-pairs, independent of the specific base-pair sequence. In contrast, no such characteristic length scale is observed in the Gaussian network model. Our study suggests that free strand entropy plays a significant role in determining the force-temperature phase diagram of the DNA.