We study how sequence heterogeneity modifies force-induced melting response in double-stranded DNA by comparing designed sequences with identical AT-GC composition but different spatial arrangements of AT- and GC-rich domains. Brownian dynamics (BD) simulations and the Gaussian network model (GNM) for DNA reveal two distinct melting regimes. At low applied forces, melting is strongly influenced by the positioning of sequence-induced weak regions and by free-end configurational entropy, leading to pronounced sequence-dependent stability. In contrast, at high forces, BD simulations reveal a force-localized melting regime in which the melting threshold is governed primarily by a finite GC-rich segment adjacent to the force-applied end. The characteristic segment contains approximately 9 GC base pairs, beyond which downstream sequence heterogeneity has little influence on the high-force melting boundary. Both BD and GNM reproduce the qualitative decrease of melting temperature with increasing force, but they differ in regimes controlled by free-end entropy and local base-pair stretching. These differences delineate the regimes where harmonic network descriptions capture the dominant trends and where an explicit dynamical description of base-pair stretching and opening fluctuation is required.
Mukherjee et al. (Wed,) studied this question.