Effect of structural dynamics and base pair sequence on the nature of excited states in DNA hairpins.

In this article, a theoretical study of the electronic and spectroscopic properties of well-defined DNA hairpins is presented. The excited states in the hairpins are described in terms of an exciton Hamiltonan model, and the structural dynamics of the DNA model systems is explicitly taken into account by molecular dynamics simulations. The results show that the model reproduces the experimentally observed absorption and circular dichroism spectra accurately in most cases. It is shown that structural disorder leads to excited states that are largely localized on a single base pair, even for regular DNA sequences consisting only of AT base pairs. Variations in the base pair sequence have a significant effect on the appearance of the spectra but also on the degree of delocalization of the excited state.

Effect of GC base pairs on charge transfer through DNA hairpins: the importance of electrostatic interactions.

DNA hairpins in which an electron donor and an electron acceptor are attached to the ends are excellent model systems for the study of charge transfer in weakly coupled pi-stacked systems. In this communication we report on a computational study of the effect of the base pair sequence in these DNA hairpins on the kinetics of charge transfer. We show that the rate of charge transfer strongly depends on the actual position of a GC base pair in a sequence that otherwise only contains AT base pairs. This can be explained by evaluating the energy landscape through which the charge travels. It is shown that including the electrostatic interaction between electron and hole can explain the experimentally observed dependence on the position of the GC in the DNA. We conclude that electrostatic interactions are important to consider when explaining the charge transfer kinetics in GC containing DNA sequences.

Limits of the plane wave approximation in the measurement of molecular properties.

Rescattering electrons offer great potential as probes of molecular properties on ultrafast timescales. The most famous example is molecular tomography, in which high harmonic spectra of oriented molecules are mapped to "tomographic images" of the relevant molecular orbitals. The accuracy of such reconstructions can be greatly affected by the distortion of scattering wave functions from their asymptotic forms due to interactions with the parent ion. We investigate the validity of the commonly used plane wave approximation in molecular tomography, showing how such distortions affect the resulting orbital reconstructions.

Modeling self-assembly processes driven by nonbonded interactions in soft materials.

This Centennial Feature Article provides an overview of research in the general area of self-assembly modeling, with particular emphasis on the self-assembly of molecules into soft nanoscale structures where the driving force for assembly is provided by nonbonded interactions (hydrogen bonds and electrostatics). The models have been developed at many different levels of theory, going all the way from simple analytical models of packing effects to atomistic descriptions using molecular dynamics methods. In between these limits are mean-field and coarse-grained models, including models for DNA, peptides, and lipids that can be used to describe the assembly of hybrid (amphiphilic) materials. Several recent applications to specific systems are discussed, including the description of peptide amphiphile assembly to make cylindrical micelles, the assembly and melting of DNA hairpins, the use of DNA tethers to assemble nanoparticles into aggregates and crystalline structures, and the use of coarse-grained lipid models to make lamellar and high-curvature phases. These examples demonstrate the difficulties associated with brute force atomistic methods, and they also show the opportunities (but uncertainties and ambiguities) associated with simpler models such as coarse-grained models. The examples also demonstrate the usefulness of successful modeling methods in the design of new materials, including an understanding of the relationship between structure and function.

Electronic excitations and spectra in single-stranded DNA.

Using density functional theory and molecular dynamics simulations, we show that delocalized states extending over three bases can be directly excited in single-stranded poly(A) DNA. The results are in semiquantitative agreement with recent experimental results for the delocalization length of these states in single- and double-stranded DNA. The structures used in these molecular dynamics calculations are validated by comparing calculated circular dichroic spectra for d(A)2 and d(A)4 with experiment. These spectra, which arise from highly stacked structures, are in good agreement with experiment, suggesting that the short delocalization in ssDNA arises in spite of strong stacking.

Effect of structural dynamics on charge transfer in DNA hairpins.

We present a theoretical study of the positive charge transfer in stilbene-linked DNA hairpins containing only AT base pairs using a tight-binding model that includes a description of structural fluctuations. The parameters are the charge transfer integral between neighboring units and the site energies. Fluctuations in these parameters were studied by a combination of molecular dynamics simulations of the structural dynamics and density functional theory calculations of charge transfer integrals and orbital energies. The fluctuations in both parameters were found to be substantial and to occur on subpicosecond time scales. Tight-binding calculations of the dynamics of charge transfer show that for short DNA hairpins (<4 base pairs) the charge moves by a single-step superexchange mechanism with a relatively strong distance dependence. For longer hairpins, a crossover to a fluctuation-assisted incoherent mechanism was found. Analysis of the charge distribution during the charge transfer process indicates that for longer bridges substantial charge density builds up on the bridge, but this charge density is mostly confined to the adenine next to the hole donor. This is caused by the electrostatic interaction between the hole on the AT bridge and the negative charge on the hole donor. We conclude both that the relatively strong distance dependence for short bridges is mostly due to this electrostatic interaction and that structural fluctuations play a critical role in the charge transfer, especially for longer bridge lengths.

Structure and electronic spectra of DNA mini-hairpins with G(n):C(n) stems.

The solution structure of a synthetic DNA mini-hairpin possessing a stilbenediether linker and three G:C base pairs has been obtained using (1)H NMR spectral data and constrained torsion angle molecular dynamics. Notable features of this structure include a compact hairpin loop having a short stilbene-guanine plane-to-plane distance and approximate B-DNA geometry for the three base pairs. Comparison of the electronic spectra of mini-hairpins having one-to-four G:C base pairs and stilbenediether or hexamethyleneglycol linkers reveals the presence of features in the UV and CD spectra of the stilbene-linked hairpins that are not observed for the ethyleneglycol-linked hairpins. Investigation of the electronic structure of a stilbene-linked hairpin having a single G:C base pair by means of time-dependent density functional theory shows that the highest occupied molecular orbital, but not the lowest unoccupied molecular orbital, is delocalized over the stilbene and adjacent guanine. The calculated UV and CD spectra are highly dependent upon hairpin conformation, but reproduce the major features of the experimental spectra. These results illustrate the utility of an integrated experimental and theoretical approach to understanding the complex electronic spectra of pi-stacked chromophores.

Radiation damage to DNA: electron scattering from the backbone subunits.

In the context of damage to DNA by low energy electrons, we carry out calculations of electron scattering from tetrahydrofuran and phosphoric acid, models of the subunits in the DNA backbone, as a first step in simulating the electron capture process that occurs in the cell. In the case of tetrahydrofuran, we also compare with previous theoretical and experimental data. A comparison of the shape of the resonant structures to virtual orbitals is also performed to gain insight into the systematic connections with electron scattering from similar molecules and dissociative electron attachment experiments.

Low-energy electron scattering from DNA and RNA bases: shape resonances and radiation damage.

Calculations are carried out to determine elastic-scattering cross sections and resonance energies for low-energy electron impact on uracil and on each of the DNA bases (thymine, cytosine, adenine, and guanine), for isolated molecules in their equilibrium geometry. Our calculations are compared with the available theory and experiment. We also attempt to correlate this information with experimental dissociation patterns through an analysis of the temporary anion structures that are formed by electron capture in shape resonances.

Electron-molecule scattering calculations in a 3D finite element R-matrix approach.

We have implemented a three-dimensional finite element approach, based on tricubic polynomials in spherical coordinates, which solves the Schrodinger equation for scattering of a low energy electron from a molecule, approximating the electron exchange as a local potential. The potential is treated as a sum of three terms: electrostatic, exchange, and polarization. The electrostatic term can be extracted directly from ab initio codes (GAUSSIAN 98 in the work described here), while the exchange term is approximated using different local density functionals. A local polarization potential approximately describes the long range attraction to the molecular target induced by the scattering electron.