Influence of a charged graphene surface on the orientation and conformation of covalently attached oligonucleotides: a molecular dynamics study.

Molecular dynamics (MD) simulations of single-stranded (ss) and double-stranded (ds) oligonucleotides anchored via an aliphatic linker to a graphene surface were performed in order to investigate the role of the surface charge density in the structure and orientation of attached DNA. Two types of interactions of DNA with the surface are crucial for the stabilisation of the DNA-surface system. Whereas for a surface with a zero or low positive charge density the dispersion forces between the base(s) and the surface dominate, the higher charge densities applied on the surface lead to a strong electrostatic interaction between the phosphate groups of DNA, the surface and the ions. At high-charge densities, the interaction of the DNA with the surface is strongly affected by the formation of a low-mobility layer of counterions compensating for the charge of the surface. A considerable difference in the behaviour of the ds-DNA and ss-DNA anchored to the layer was observed. The ds-DNA interacts with the surface at low- and zero-charge densities exclusively by the nearest base pair. It keeps its geometry close to the canonical B-DNA form, even at surfaces with high-charge densities. The ss-DNA, owing to its much higher flexibility, has a tendency to maximise the attraction to the surface exploiting more bases for the interaction. The interaction of the polar amino group(s) of the base(s) of ss-DNA with a negatively charged surface also contributes significantly to the system stability.

A measure of bending in nucleic acids structures applied to A-tract DNA.

A method is proposed to measure global bending in DNA and RNA structures. It relies on a properly defined averaging of base-fixed coordinate frames, computes mean frames of suitably chosen groups of bases and uses these mean frames to evaluate bending. The method is applied to DNA A-tracts, known to induce considerable bend to the double helix. We performed atomistic molecular dynamics simulations of sequences containing the A(4)T(4) and T(4)A(4) tracts, in a single copy and in two copies phased with the helical repeat. Various temperature and salt conditions were investigated. Our simulations indicate bending by roughly 10 degrees per A(4)T(4) tract into the minor groove, and an essentially straight structure containing T(4)A(4), in agreement with electrophoretic mobility data. In contrast, we show that the published NMR structures of analogous sequences containing A(4)T(4) and T(4)A(4) tracts are significantly bent into the minor groove for both sequences, although bending is less pronounced for the T(4)A(4) containing sequence. The bending magnitudes obtained by frame averaging are confirmed by the analysis of superhelices composed of repeated tract monomers.

On the parameterization of rigid base and basepair models of DNA from molecular dynamics simulations.

A method is described to extract a complete set of sequence-dependent material parameters for rigid base and basepair models of DNA in solution from atomistic molecular dynamics simulations. The method is properly consistent with equilibrium statistical mechanics, leads to effective shape, stiffness and mass parameters, and employs special procedures for treating spontaneous torsion angle flips and H-bond breaks, both of which can have a significant effect on the results. The method is accompanied by various analytical consistency checks that can be used to assess the equilibration of statistical averages, and different modeling assumptions pertaining to the rigidity of the bases and basepairs and the locality of the quadratic internal energy. The practicability of the approach is verified by estimating complete parameter sets for the 16-basepair palindromic oligomer G(TA)(7)C simulated in explicit water and counterions. Our results indicate that the method is capable of resolving sequence-dependent variations in each of the material parameters. Moreover, they show that the assumptions of rigidity and locality hold rather well for the base model, but not for the basepair model. For the latter, it is shown that the non-local nature of the internal energy can be understood in terms of a certain compatibility relation involving Schur complements.

Sequence-dependent elastic properties of DNA.

Harmonic elastic constants of 3-11 bp duplex DNA fragments were evaluated using four 5 ns unrestrained molecular dynamics simulation trajectories of 17 bp duplexes with explicit inclusion of solvent and counterions. All simulations were carried out with the Cornell et al. force-field and particle mesh Ewald method for long-range electrostatic interactions. The elastic constants including anisotropic bending and all coupling terms were derived by analyzing the correlations of fluctuations of structural properties along the trajectories. The following sequences have been considered: homopolymer d(ApA)(n) and d(GpG)(n), and alternating d(GPC)(n) and d(APT)(n). The calculated values of elastic constants are in very good overall agreement with experimental values for random sequences. The atomic-resolution molecular dynamics approach, however, reveals a pronounced sequence-dependence of the stretching and torsional rigidity of DNA, while sequence-dependence of the bending rigidity is smaller for the sequences considered. The earlier predicted twist-bend coupling emerged as the most important cross-term for fragments shorter than one helical turn. The calculated hydrodynamic relaxation times suggest that damping of bending motions may play a role in molecular dynamics simulations of long DNA fragments. A comparison of elasticity calculations using global and local helicoidal analyses is reported. The calculations reveal the importance of the fragment length definition. The present work shows that large-scale molecular dynamics simulations represent a unique source of data to study various aspects of DNA elasticity including its sequence-dependence.