2026/07/29 by Bidisha Mukherjee, Amit Raj Singh, Garima Mishra
Biochemistry, Genetics and Molecular Biology · Chemistry · Physics and Astronomy · #Advanced Physical and Chemical Molecular Interactions #DNA and Nucleic Acid Chemistry #Force Microscopy Techniques and Applications
paper · pdf · doi:10.1088/1361-648x/ae9235
openalex publication_date 2026/07/29 · openalex created_date 2026/07/30 · openalex updated_date 2026/07/31
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.