Understanding sequence effect in DNA bending elasticity by molecular dynamic simulations

Abstract Structural elasticity of double-strand DNAs is very important for their biological functions such as DNA-ligand binding and DNA-protein recognition. By all-atom molecular dynamics simulations, we investigated the bending elasticity of DNA with three typical sequences including poly(A)-poly(T) (AA-TT), poly(AT)-poly(TA) (AT-TA), and a generic sequence (GENE). Our calculations indicate that, AA-TT has an apparently larger bending persistence length ( P ∼63 nm) than GENE ( P ∼49 nm) and AT-TA ( P ∼48 nm) while the persistence length of AT-TA is only very slightly smaller than that of GENE, which agrees well with those from existing works. Moreover, through extensive electrostatic calculations, we found that the sequence-dependent bending elasticity is attributed to the sequence-dependent electrostatic bending energy for AA-TT, AT-TA and GENE, which is coupled to their backbone structures. Particularly, the apparently stronger bending stiffness of AA-TT is attributed to its narrower minor groove. Interestingly, for the three DNAs, we predicted the non-electrostatic persistence length of ∼17 nm, thus electrostatic interaction makes the major contribution to DNA bending elasticity. The mechanism of electrostatic energy dominating sequence effect in DNA bending elasticity is furtherly illustrated through the electrostatic calculations for a grooved coarse-grained DNA model where minor groove width and other microscopic structural parameters can be artificially adjusted.