Double helix crookedness regulates the twist–stretch coupling: A quantitative molecular dynamics analysis

DNA conformation and twist-stretch coupling play a fundamental role in multiple biological processes. The contrasting elongation of DNA and shortening of RNA upon overwinding hint at a helix-related twist-stretch coupling, yet elucidating the underlying relationship between conformation and twist-stretch coupling is still a challenge. Here, our molecular dynamics simulations reveal that DNA sequence-dependent variation in helical structure can significantly regulate its twist-stretch coupling, even inducing shortening upon overwinding. In particular, our simulations reveal a non-monotonic relationship between the twist-stretch coupling parameter dL/dN and DNA conformation quantified by DNA crookedness β: dL/dN first increases and then decreases as β increases. Empirically, the variation in dL/dN arises from the evolution of helical radius with the stretching force. Further analysis, at the base-pair level, quantitatively reveals that this relationship is primarily driven by the variation of base-pair center distance Lbp upon overwinding, which arises mainly from slide and rise base-pair parameters. These results establish a structure-elasticity framework for the twist-stretch coupling of dsDNA.