Charge transport properties of ideal and natural DNA segments, as mutation detectors.

DNA sequences of ideal and natural geometries are examined, studying their charge transport properties as mutation detectors. Ideal means textbook geometry. Natural means naturally distorted sequences; geometry taken from available databases. A tight-binding (TB) wire model at the base-pair level is recruited, together with a transfer matrix technique. The relevant TB parameters are obtained using a linear combination of all valence orbitals of all atoms, using geometry, either ideal or natural, as the only input. The investigated DNA sequences contain: (i) point substitution mutations - specifically, the transitions guanine (G) ↔ adenine (A) - and (ii) sequences extracted from human chromosomes, modified by expanding the cytosine-adenine-guanine triplet [(CAG)n repeats] to mimic the following diseases: (a) Huntington's disease, (b) Kennedy's disease, (c) Spinocerebellar ataxia 6, (d) Spinocerebellar ataxia 7. Quantities such as eigenspectra, density of states, transmission coefficients, and the - more experimentally relevant - current-voltage (I-V) curves are studied, intending to find adequate features to recognize mutations. To this end, the normalised deviation of the I-V curve from the origin (NDIV) is also defined. The features of the NDIV seem to provide a clearer picture, being sensitive to the number of point mutations and allowing to characterise the degree of danger of developing the aforementioned diseases.

LCAO Electronic Structure of Nucleic Acid Bases and Other Heterocycles and Transfer Integrals in B-DNA, Including Structural Variability.

To describe the molecular electronic structure of nucleic acid bases and other heterocycles, we employ the Linear Combination of Atomic Orbitals (LCAO) method, considering the molecular wave function as a linear combination of all valence orbitals, i.e., 2s, 2px, 2py, 2pz orbitals for C, N, and O atoms and 1s orbital for H atoms. Regarding the diagonal matrix elements (also known as on-site energies), we introduce a novel parameterization. For the non-diagonal matrix elements referring to neighboring atoms, we employ the Slater-Koster two-center interaction transfer integrals. We use Harrison-type expressions with factors slightly modified relative to the original. We compare our LCAO predictions for the ionization and excitation energies of heterocycles with those obtained from Ionization Potential Equation of Motion Coupled Cluster with Singles and Doubles (IP-EOMCCSD)/aug-cc-pVDZ level of theory and Completely Normalized Equation of Motion Coupled Cluster with Singles, Doubles, and non-iterative Triples (CR-EOMCCSD(T))/aug-cc-pVDZ level of theory, respectively, (vertical values), as well as with available experimental data. Similarly, we calculate the transfer integrals between subsequent base pairs, to be used for a Tight-Binding (TB) wire model description of charge transfer and transport along ideal or deformed B-DNA. Taking into account all valence orbitals, we are in the position to treat deflection from the planar geometry, e.g., DNA structural variability, a task impossible for the plane Hückel approach (i.e., using only 2pz orbitals). We show the effects of structural deformations utilizing a 20mer evolved by Molecular Dynamics.

Effects of Structural Dynamics on Charge Carrier Transfer in B-DNA: A Combined MD and RT-TDDFT Study.

Hole transfer along the axis of duplex DNA has been the focus of physical chemistry research for decades, with implications in diverse fields, from nanotechnology to cell oxidative damage. Computational approaches are particularly amenable for this problem, to complement experimental data for interpretation of transfer mechanisms. To be predictive, computational results need to account for the inherent mobility of biological molecules during the time frame of experimental measurements. Here, we address the structural variability of B-DNA and its effects on hole transfer in a combined molecular dynamics (MD) and real-time time-dependent density functional theory (RT-TDDFT) study. Our results show that quantities that characterize the charge transfer process, such as the time-dependent dipole moment and hole population at a specific site, are sensitive to structural changes that occur on the nanosecond time scale. We extend the range of physical properties for which such a correlation has been observed, further establishing the fact that quantitative computational data on charge transfer properties should include statistical averages. Furthermore, we use the RT-TDDFT results to assess an efficient tight-binding method suitable for high-throughput predictions. We demonstrate that charge transfer, although affected by structural variability, on average, remains strong in AA and GG dimers.

Quasi-Periodic and Fractal Polymers: Energy Structure and Carrier Transfer.

We study the energy structure and the coherent transfer of an extra electron or hole along aperiodic polymers made of N monomers, with fixed boundaries, using B-DNA as our prototype system. We use a Tight-Binding wire model, where a site is a monomer (e.g., in DNA, a base pair). We consider quasi-periodic (Fibonacci, Thue-Morse, Double-Period, Rudin-Shapiro) and fractal (Cantor Set, Asymmetric Cantor Set) polymers made of the same monomer (I polymers) or made of different monomers (D polymers). For all types of such polymers, we calculate the highest occupied molecular orbital (HOMO) eigenspectrum and the lowest unoccupied molecular orbital (LUMO) eigenspectrum, the HOMO-LUMO gap and the density of states. We examine the mean over time probability to find the carrier at each monomer, the frequency content of carrier transfer (Fourier spectra, weighted mean frequency of each monomer, total weighted mean frequency of the polymer), and the pure mean transfer rate k. Our results reveal that there is a correspondence between the degree of structural complexity and the transfer properties. I polymers are more favorable for charge transfer than D polymers. We compare k ( N ) of quasi-periodic and fractal sequences with that of periodic sequences (including homopolymers) as well as with randomly shuffled sequences. Finally, we discuss aspects of experimental results on charge transfer rates in DNA with respect to our coherent pure mean transfer rates.