B-DNA to Zip-DNA: Simulating a DNA Transition to a Novel Structure with Enhanced Charge-Transport Characteristics

Abstract

The forced extension of a DNA segment is studied in a series of steered molecular dynamics simulations, employing a broad range of pulling forces. Throughout the entire force range, the formation of a zipper-like (zip-) DNA structure is observed. In that structure, first predicted by Lohikoski et al., the bases of the DNA strands interdigitate with each other and form a single-base aromatic stack. Similar motifs, albeit only a few base pairs in extent, have been observed in experimental crystal structures. Analysis of the dynamics of structural changes in pulled DNA shows that S-form DNA, thought to be adopted by DNA under applied force, serves as an intermediate between B-DNA and zip-DNA. Therefore, the phase transition plateau observed in force–extension curves of DNA is suggested to reflect the B-DNA to zip-DNA structural transition. Electronic structure analysis of purine bases in zip-DNA indicates a several-fold to order of magnitude increase in the π–π electronic coupling among nearest-neighbor nucleobases, compared to B-DNA. We further observe that zip-DNA does not require base pair complementarity between DNA strands, and we predict that the increased electronic coupling in zip-DNA will result in a much higher rate of charge transfer through an all-purine zip-DNA compared to B-DNA of equal length.

Overstretching of B-DNA with various pulling protocols: Appearance of structural polymorphism and S-DNA

“…For instance, Balaeff et al [48] observed a B-to-zip DNA transition instead of B-to-S DNA transition using steered molecular dynamics simulations. They proposed that S-DNA could be an intermediate state during this transition.…”

The transition mechanism of DNA overstretching: a microscopic view using molecular dynamics

“…In fact, the extended DNA has been found to be consistent with a multiplicity of possible structures, from two separated strands of singlestranded DNA (ss-DNA) formed as a result of melting [14,15] to a variety of extended ds conformations (S-forms). These putative structures, including the S-ladder, a straightened DNA with preserved base pairing [16], and the S-zipper [17], are all characterized by variously coupled strands with reduced helicity. Even recently, a number of studies on the subject have appeared, either discarding [18,19] or supporting [8][9][10] the existence of the S state.…”

“…Initially, steered MD simulations of torsionally unconstrained DNA molecules were employed [16,17,[26][27][28][29]. According to this approach, the overstretching experiments are simulated taking explicitly into account the presence of a pulling force.…”

Dynamics and Efficiency of Hole Transport in LNA:DNA Hybrid Diblock Oligomers

“…10,12 Nuclear and solvent reorganization have been suggested as factors responsible for the slow rates of hole transport in DNA. 13 Among the backbone modifications that have drawn attention as alternatives to the dexoyribose of DNA in studies of charge transport are the stretched deoxyribose backbone (Zip-DNA), 14 peptide nucleic acids (PNA), 15,16 and locked nucleic acids (LNA, Chart 1b). 17,18 Molecular dynamics (MD) simulations for Zip-DNA reveal enhanced intrastrand base stacking leading to predictions of rapid charge transport, which remain to be experimentally tested.…”