Role of bubble positioning in force induced melting of DNA

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.