Sequence Effect on the Bending Elasticity of Double-Stranded DNA

The sequence effect on double-stranded DNA elasticity is crucial for DNA-protein binding and recognition. Here, we employed extensive all-atom molecular dynamics simulations to investigate the relationships between DNA sequences and its bending elasticity through involving DNA crookedness for describing sequence-dependent local bends of base pair centers. Our results demonstrated that the increase of DNA crookedness due to its sequence leads to the decrease of DNA bending stiffness. Based on such relationship, we established a predictive model that quantitatively connects DNA bending persistence length and its sequence, which was validated by extensive experimental data. Moreover, our analyses revealed that the fluctuation of base-pair inclination along DNA and local base pair Lennard-Jones interactions between atoms in rings and major grooves, rather than total atoms of base pair, play critical roles in sequence-dependent DNA bending flexibility. The software of the predictive model is freely available at https://github.com/Dong-group/Pdna-seq.