π Stack Structure and Hole Transfer Couplings in DNA Hairpins and DNA. A Combined QM/MD Study

Abstract

Many key characteristics of hole transfer (HT) in DNA have been derived from spectroscopic studies of DNA hairpins. Because the capping groups in the hairpins can remarkably influence the structure and flexibility of the pi stack, and therefore, the charge transfer rate, the question arises of whether the HT parameters obtained for hairpins may be transferred to DNA oligomers. On the basis of large-time scale QM/MD simulations, we compare structural and electronic parameters of AT stacks in hairpins and DNA oligomers. We find that even in short hairpins, Sa-AA-Sd and Sa-AAA-Sd, the effects of the capping chromophores on the structure of the pi stack and the HT couplings properly averaged over MD trajectories are relatively small, and therefore, the hairpins are good models to study hole transfer through DNA. By contrast, the calculations of the electronic couplings based on the average structures of the systems lead to essential errors in the HT rate and the misleading statement that the charge transfer properties of DNA domains within hairpins are quite different from those of normal sequences.

Nucleic acid charge transfer: Black, white and gray

“…However, it is important to recognize that the significance of each specific mechanism is limited. Recent experiments [86, 87] and theoretical studies [53, 54, 61, 77, 82, 88, 89] show that NA structural flexibility and interactions with a dynamic solvent medium create significant modulation in NA electronic properties and CT mechanism. We show in this review (section 4), that a mixture of the mechanisms described below must be considered for any NA sequence.…”

“…Although early molecular dynamics and quantum chemical studies on oligo-peptides and proteins emphasized the effect of structural fluctuations on electronic coupling [103, 104], the computation of NA CT parameters was largely based upon idealized structures, until recently [10, 71–73], This approach has evolved over the last few years as atomistic simulations were adopted to sample NA geometries and to explore how fluctuations influence ensemble CT properties [53, 54, 57, 58, 69, 70, 74, 77–81, 89, 105, 106]. We highlight emerging views on NA-CT derived from such atomistic simulations coupled with electronic structure analysis.…”

“…Atomistic MD simulations allow sampling this diversity in environments of experimental relevance [53, 61, 69, 70, 77, 78, 81, 89]. Next, we review how fluctuations in nucleobase geometries and more global fluctuations in the nucleobase helicoidal parameters create a structurally diverse ensemble to modulate NA-CT properties.…”

DFT performance for the hole transfer parameters in DNA π stacks

“…Different computational approaches have been applied to understand the mechanisms of the HT process [3,4]. A number of theoretical investigations of HT in DNA have been recently published [5][6][7][8][9][10][11].…”

Toward DNA Conductivity: A Theoretical Perspective

“…From both the fragment orbital approach and Koopman's theorm approach, it has been found that the charge transfer between neighboring base pairs is highest when the twist angle is ∼36°, which is the twist angle for a B-DNA conformation ( Figure 3e). 33,39,40 Similarly, it has been found that the rise (D z ) affects the value of the charge-transfer integral, which decreases rapidly upon increasing the separation between the two base pairs. In a recent study, Elstner and co-workers used the fragment orbital approach to evaluate the charge-transfer parameters for a molecular dynamics (MD) trajectory in which the environmental effects were captured using a quantum mechanicsmolecular mechanics (QM/MM) coupling scheme.…”