Interaction of water with DNA single and double helix in the B conformation

The interaction energy between water and B-DNA in the single and double helix is computed at a number of planar cross sections perpendicular to the helix long axis and for a few cylindrical surfaces enclosing the helix. In addition, Monte Carlo simulations are presented for a small cluster of water around regions of energy minima. On the base of these simulations the structure of water for B-DNA in solution, the quaternary structure of B-DNA, is proposed and discussed. The intermolecular interaction used in the Monte Carlo computation has been derived from ab initio computations of complexes between water and the DNA bases, diethylphosphate, a ribose derivative, and other model compounds.     

Torsional deformation of double helix in interaction and aggregation of DNA

We incorporate sequence-dependent twisting between adjacent base pairs and torsional elasticity of double helix into the theory of DNA-DNA interaction. The results show that pairing and counterion-induced-aggregation of nonhomologous DNA are accompanied by considerable torsional deformation. The deformation tunes negatively charged phosphate strands and positively charged grooves on opposing molecules to stay "in register", substantially reducing nonideality of the helical structure of DNA. Its cost, however, makes interaction between nonhomologous DNA less energetically favorable. In particular, interaction between double helical DNA may result in sequence homology recognition and selective pairing of homologous fragments containing more than 100-200 base pairs. We also find a weak, but potentially measurable, increase in the expected counterion concentration required for aggregation of nonhomologous DNA and slightly higher solubility of such DNA above the critical concentration.     

DNA: beyond the double helix

Reciprocal exchange can be used to produce DNA motifs based on branching at the level of secondary structure. These motifs can be combined by sticky-ended cohesion to produce a variety of structures. Stick polyhedra and nanomechanical devices have been produced by self-assembly from motifs based on branched DNA. Periodic arrays with tunable surface features has also been produced; aperiodic arrangements have been used for DNA-based computation.     

Measurement of the unwinding force of a DNA double helix

The review is devoted to measurement methods of bond rupture forces in complex biological molecules, namely, the unwinding forces of a DNA double helix. Mechanical methods not affecting electromagnetically a system under study, which is especially significant for biological systems, are considered. We describe two main methods: atomic force microscopy and rupture event scanning. The latter is a new method also based on the mechanical action but it has a much simpler instrumental implementation. The capabilities of both methods are compared and they are shown to be promising to investigate chemical bond rupture forces in biological systems. The application of these methods to study the strength of chemical bonds is associated with overcoming numerous technical difficulties in both performance of measurements themselves and chemical modification of conjugated surfaces. We demonstrate the applicability of these methods not only for fundamental studies of the strength of chemical bonds determining the stability and the related possibility of functioning of three-dimensional biomolecular complexes, but also for the design of biosensors based on the mechanical effect (quartz crystal microbalance, QCM), e.g., with an opportunity of rapid analysis of DNA.     

Iso-energy cutoff for the calculation of interionic potential of mean force in water

An iso-energy cutoff scheme is introduced for the calculation of the potential of mean force between two ions in water. The cutoff criterion is based on the optimal interaction of the water dipole with the ion pair, for which analytical expressions are derived. Formulas are also derived to characterize the solvent reorganization contribution to the potential of mean force. Treatment of the contributions from waters outside the cutoff is also discussed. © 1994 John Wiley & Sons, Inc.     

Linker effect of ferrocenylnaphthalene diimide ligands in the interaction with double stranded DNA

Ferrocenylnaphthalene diimide ligands 1-7 were synthesized by joining a piperazino or N-methylamino linker of the naphthalene diimide skeleton with ferrocenecarboxylic, ferroceneacetic, or ferrocenepropionic parts. Their interaction with double stranded DNA (dsDNA) was studied kinetically and electrochemically. Association rate constants of these ligands were found to correlate with their intramolecular stacking ability between the ferrocene and naphthalene diimide planes: ligands which can adopt a stacked conformation in buffer solution were unfavorable in the association with dsDNA, resulting in a smaller association rate constant. Dissociation rate constants of these ligands carrying the bulky piperazino linker were smaller than that of those carrying an N-methylamino one. Binding constants were dictated by the balance of these two factors. These ligands were applied to the electrochemical detection of the amount of dsDNA on the electrode. Ligand 6 having the highest affinity for dsDNA gave rise to the largest current increase upon dsDNA formation in the electrochemical hybridization assay.     

DNA quality control by conformational readout on the undamaged strand of the double helix

Synthetic DNA probes were incubated in human cell extracts to dissect the early step of bulky lesion recognition in the nucleotide excision repair pathway. Excision was induced upon combination of the target adduct with either a two-sided bulge, involving both the damaged sequence and its undamaged partner strand, or a one-sided bulge, affecting exclusively the undamaged complementary sequence. Surprisingly, the same adduct became refractory to repair when only the modified strand was bulged out of the double helix. Adduct removal was further dependent on an intact opposing strand and, at carcinogen-DNA adducts, the assembly of excision complexes was triggered by a single flipped-out deoxyribonucleotide in the complementary sequence. These findings describe a mechanism of molecular readout in DNA repair that, unexpectedly, is entirely confined to the undamaged side of the double helix.     

Control of a double helix DNA assembly by use of cross-linked oligonucleotides

Disulfide cross-linked oligonucleotides for connecting two DNA double helixes have been designed, synthesized, and characterized. Employing these cross-linked oligonucleotides, two double helixes can be arranged side by side, and the orientations can be controlled both in parallel and antiparallel ways by addition of a specific complementary DNA strand.     

Conserved patterns in backbone torsional changes allow for single base flipping from duplex DNA with minimal distortion of the double helix

Base flipping is a structural mechanism common to many DNA processing and repair enzymes. Changes in the local backbone torsions that occur during base flipping and the effect of environment on their behavior are of particular interest in understanding different base flipping mechanisms. In the present study, structures sampled during umbrella sampling molecular dynamics (MD) simulations of base flipping in aqueous and protein-bound environments, carried out with two different MD simulation strategies, are analyzed to find the most significant phosphodiester backbone distortions in the vicinity of the flipping base. Torsional sampling on the 5' side of the flipping base during flipping through the major groove shows similarities to the torsional sampling on the 3' side during flipping through the minor groove and vice versa. In differing environments, this behavior varies only marginally. These compensating torsional changes in the DNA backbone on 5' and 3' sides of the flipping base limit overall distortion of the DNA double helix during single base flipping. Rotameric intermediate states observed during base flipping are identified and postulated to be metastable states implicated in both large-scale structural changes and functional effects of chemical modifications in DNA.     

DFT study of polymorphism of the DNA double helix at the level of dinucleoside monophosphates

We apply DFT calculations to deoxydinucleoside monophosphates (dDMPs) which represent minimal fragments of the DNA chain to study the molecular basis of stability of the DNA duplex, the origin of its polymorphism and conformational heterogeneity. In this work, we continue our previous studies of dDMPs where we detected internal energy minima corresponding to the “classical” B conformation (BI‐form), which is the dominant form in the crystals of oligonucleotide duplexes. We obtained BI local energy minima for all existing base sequences of dDMPs. In the present study, we extend our analysis to other families of DNA conformations, successfully identifying A, BI, and BII energy minima for all dDMP sequences. These conformations demonstrate distinct differences in sugar ring puckering, but similar sequence‐dependent base arrangements. Internal energies of BI and BII conformers are close to each other for nearly all the base sequences. The dGpdG, dTpdG, and dCpdA dDMPs slightly favor the BII conformation, which agrees with these sequences being more frequently experimentally encountered in the BII form. We have found BII‐like structures of dDMPs for the base sequences both existing in crystals in BII conformation and those not yet encountered in crystals till now. On the other hand, we failed to obtain dDMP energy minima corresponding to the Z family of DNA conformations, thus giving us the ground to conclude that these conformations are stabilized in both crystals and solutions by external factors, presumably by interactions with various components of the media. Overall the accumulated computational data demonstrate that the A, BI, and BII families of DNA conformations originate from the corresponding local energy minimum conformations of dDMPs, thus determining structural stability of a single DNA strand during the processes of unwinding and rewinding of DNA. © 2010 Wiley Periodicals, Inc. Int J Quantum Chem 110:2548–2559, 2010     

DFT approach to calculate electronic transfer through a segment of DNA double helix

The electronic structures of an entire segment of a DNA molecule were calculated in its single‐strand and double‐helix cases using the DFT method with an overlapping dimer approximation and negative factor counting method. The hopping conductivity of the segment was calculated by the random walk theory from the results of energy levels and wave functions obtained. The results of the single‐strand case show that the DFT method is quantitatively in agreement with that of the HF MP2 method. The results for the double helix are in good agreement with that of the experimental data. Therefore, the long‐range electron transfer through the DNA molecule should be caused by hopping of electronic charge carriers among different energy levels whose corresponding wave functions are localized at different bases of the DNA molecule. © 2000 John Wiley & Sons, Inc. J Comput Chem 21: 1109–1117, 2000     

Conjugation of testosterone modifies the interaction of mono-functional cationic platinum(II) complexes with DNA, causing significant alterations to the DNA helix

Previously a range of androgen conjugates with non-conventional platinum(II) complexes have been synthesised with the aim of enhancing cellular delivery, and which have shown increased cytotoxic activity compared with non-steroidal compounds (M. J. Hannon et al., Dalton Trans., 2010, DOI: 10.1039/c0dt00838a). To further study this, the complexes have been assessed for their ability to bind to and alter the structure of DNA. All platinum(II) complexes studied herein bind to model nucleo-bases and DNA, but to our surprise, testosterone-based complexes caused the DNA helix to undergo significant unwinding and bending, whereas non-steroidal control complexes caused minimal structural alterations. These effects are similar to those cisplatin induces on DNA structure despite the fact that these compounds produce a monofunctional lesion. This ability attributed to interactions between the DNA helix and bulky steroidal skeleton of testosterone, coupled with the enhanced cellular delivery induced by the steroid make the steroid approach an exciting way to explore non-conventional platinum drug delivery.     

X-Ray diffraction analyses of the natural isoquinoline alkaloids Berberine and Sanguinarine complexed with double helix DNA d(CGTACG)

The first crystal structures of Berberine and Sanguinarine intercalated with a d(CGTACG)(2) DNA sequence were obtained by X-ray diffraction analysis at 2.3 ? resolution. Both drugs join the end of two "two-molecules" DNA units, stacked in a non-classic intercalation site formed by six bases. Sanguinarine interacts with d(CGTACG)(2) DNA in its iminium form.     

Understanding electron attachment to the DNA double helix: the thymidine monophosphate-adenine pair in the gas phase and aqueous solution

Electron attachment to the 2'-deoxythymidine-5'-monophosphate-adenine pairs (5'-dTMPH-A and 5'-dTMP(-)-A) has been investigated at a carefully calibrated level of theory (B3LYP/DZP++) to investigate the electron-accepting properties of thymine (T) in the DNA double helix under physiological conditions. All molecular structures have been fully optimized in vacuo and in solution. The adiabatic electron affinity of 5'-dTMPH-A in the gas phase has been predicted to be 0.67 eV. Solvent effects greatly increase the electron capture ability of 5'-dTMPH-A. In fact, the adiabatic electron affinity increases to 2.04 eV with solvation. The influence of the solvent environment on the electron-attracting properties of 5'-dTMPH-A arises not only from the stabilization of the corresponding radical anion through charge-dipole interactions, but also by changing the distribution of the unpaired electron in the molecular system. The unpaired electron is covalently bound even during vertical attachment, due to the solvent effects. Solvent effects also weaken the pairing interaction in the thymidine monophosphate-adenine complexes. The phosphate deprotonation is found to have a relatively minor influence on the capture of electrons by the 5'-dTMPH-A species in aqueous solution. The electron distributions, natural population analysis, and geometrical features of the models examined illustrate that the influence of the phosphate deprotonation is limited to the phosphate moiety in aqueous solution. Therefore, it is reasonable to expect that electron attachment to nucleotides will be independent of monovalent counterions in the vicinity of the phosphate group in aqueous solution.