The Role of Unconventional Hydrogen Bonds in Determining BII Propensities in B-DNA

Abstract

An accurate understanding of DNA backbone transitions is likely to be the key for elucidating the puzzle of the intricate sequence-dependent mechanical properties that govern most of the biologically relevant functions of the double helix. One factor believed to be important in indirect recognition within protein-DNA complexes is the combined effect of two DNA backbone torsions (ε and ζ) which give rise to the well-known BI/BII conformational equilibrium. In this work we explain the sequence dependent BII propensity observed in RpY steps (R = purine; Y = pyrimidine) at the tetranucleotide level with the help of a previously undetected C-H···O contact between atoms belonging to adjacent bases. Our results are supported by extensive multi-microsecond molecular dynamics simulations from the Ascona B-DNA Consortium, high-level quantum mechanical calculations, and data mining of the experimental structures deposited in the Protein Data Bank.

Sequence-dependent response of DNA to torsional stress: a potential biological regulation mechanism

“…The four oligomers studied in this work are listed in Table 1 . These oligomers were chosen so as to include pyrimidine-p-purine (YpR) and purine-p-purine (RpR) steps that have already been shown to be able to exist in high and low twist states ( 28 , 43 , 44 ). Table 1 lists the presence of these steps within the segment of each oligomer that will be subjected to twist restraints (namely, base pairs 3–15).…”

How global DNA unwinding causes non-uniform stress distribution and melting of DNA

“…Segments storing more elastic energy also exhibit significant transitions in the backbone structure (Fig 7 and S11-S31 Figs in S1 File). Since, C/G segments exhibit a higher propensity for adopting a BII state in unrestrained DNA [12,44,45,46] these segments have also a higher capacity towards transitions from BII to BI states (which overall relaxes unwinding stress, see previous paragraphs). Especially, at high supercoiling (before melting) significant increase in the BI propensity is observed along the DNA sequences mostly in the G/C-rich segments (orange bars in Fig 7, see also Fig 8).…”

How methyl–sugar interactions determine DNA structure and flexibility

“…In previous Molecular Dynamics (MD) simulation and NMR based studies, the sequence dependent population of BI/BII states and their impact on DNA’s structure has been extensively investigated (13–18). Recently, the sequence dependence of BI/BII states was systematically analyzed using trajectories obtained by the Ascona B-DNA consortium (ABC) based on a database of extensive MD simulations of DNA oligomers containing all 136 distinct tetranucleotide sequences (15,19). It was found that the sequence dependent formation of unconventional hydrogen bonds between base and backbone atoms plays a key role in stabilizing the BII substate (a C8-H8..O3′, between purine base and backbone in case of RpR and YpR steps; and a C6-H6..O3′ contact in RpY and YpY steps(15,19)).…”

“…Recently, the sequence dependence of BI/BII states was systematically analyzed using trajectories obtained by the Ascona B-DNA consortium (ABC) based on a database of extensive MD simulations of DNA oligomers containing all 136 distinct tetranucleotide sequences (15,19). It was found that the sequence dependent formation of unconventional hydrogen bonds between base and backbone atoms plays a key role in stabilizing the BII substate (a C8-H8..O3′, between purine base and backbone in case of RpR and YpR steps; and a C6-H6..O3′ contact in RpY and YpY steps(15,19)). The formation of a (base) C-H..O3′ (sugar) hydrogen bond contact perfectly correlated with the formation and percentage of BII states at dinucleotide steps in DNA.…”