Charge transport characteristics of short double-strand DNA including mismatches are studied within a methodology combining molecular-dynamics ͑MD͒ simulations and electronic-structure calculations based on a fragment orbital approach. Electronic parameters and transmission probabilities are computed along the MD trajectory. We find that in the course of the MD simulation the energetic position of frontier orbitals may be interchanged. As a result, the highest-occupied molecular orbital can temporarily have a large weight on the backbones as a function of time. This shows that care must be taken when projecting the electronic structure onto effective low-dimensional model Hamiltonians to calculate transport properties. Further, the transport calculations indicate a suppression of the charge migration efficiency when introducing a single GT or AC mismatch in the DNA sequence.
We present a detailed study of the charge transport characteristics of double-stranded DNA oligomers including the oxidative damage 7, 8-dihydro-8-oxoguanine (8-oxoG). The problem is treated by a hybrid methodology combining classical molecular dynamics simulations and semiempirical electronic structure calculations to formulate a coarse-grained charge transport model. The influence of solvent-and DNA-mediated structural fluctuations is encoded in the obtained time series of the electronic charge transfer parameters. Within the Landauer approach to charge transport, we perform a detailed analysis of the conductance and current time series obtained by sampling the electronic structure along the molecular dynamics trajectory, and find that the inclusion of 8-oxoG damages into the DNA sequence can induce a change in the electrical response of the system. However, solvent-induced fluctuations tend to mask the effect, so that a detection of such sequence modifications via electrical transport measurements in a liquid environment seems to be difficult to achieve. I n aerobic organisms, oxidative DNA damage frequently occurs during normal metabolism and upon exposure to light or other ionizing radiation. 7,8-Dihydro-8-oxoguanine (8-oxoG) is one of the most common forms of oxidative DNA damage found in human cells, where a H8 atom in guanine is replaced by an O8 atom, and a H7 atom is added to N7 ( Figure 1). When DNA polymerase encounters 8-oxoG during the DNA replication process, it frequently inserts a mismatched base (adenine) instead of cytosine, leading to G:C → T:A transversions, 1 which are commonly found in mutations associated with age-related diseases and human cancers. Although distinct changes were found in the backbone structure of a 25-base single-stranded DNA (ssDNA) with single 8-oxoG substitutions by Fourier transform-infrared analysis, 3 it has been known that 8-oxoG:C base-pairs have only a minor effect on double-stranded DNA (dsDNA) structure and stability.4,5 Thus, there is an intriguing question as to how the DNA repair enzyme locates 8-oxoG lesions within the entire human genome. In a recent experiment, Markus et al. 6 suggested that 8-oxoG has unique electronic properties and that modulations in the electronic properties might be related to the mechanism of recognizing lesions. They used laser-based methods to investigate various oligomers adsorbed on gold substrates as self-assembled monolayers, and found that the highest occupied molecular orbital (HOMO) appears at a higher energy when 8-oxoG is inserted into the sequence than in unmodified oligomers. The electronic property changes induced by the 8-oxoG lesions suggest the possibility of detecting in vitro 8-oxoG in a DNA sequence by examining the modification of its electrical response; this is expected to have high relevance in, e.g., the development of biosensors based on modifications of the electrical response. 7,8 Electrical detection of an 8-oxo-deoxyguanosine was proposed by Tsutsui et al. 9 by measuring the tunneling cur...
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