Preopening of the DNA base pairs

The lower‐energy stable structures of the A?T base pair are revealed under a search of its potential energy surface in the vicinity of its Watson–Crick configuration performed at the PM3 computational level. Their properties and the mutual position of the nucleic acid bases A and T in these structures allow to partition them into three classes: partially preopened, stretched, and fully preopened. The preferable monohydration sites of the preopened, stretched, and fully preopened pairs are also determined. It is demonstrated, first, that the monohydration of the A?T pair at particular sites favors a base pair preopeness and, second, that a binding of the water molecule to the preopened A?T base pair on the major groove side enhances its stabilization. It is also shown that water molecule placing in the vicinity of the central H bond of the A?T pair significantly facilitates its preopening. © 2001 John Wiley & Sons, Inc. Int J Quant Chem 82: 193–204, 2001     

Halogen bonding in DNA base pairs

Halogen bonding (R-X···Y) is a qualitative analogue of hydrogen bonding that may prove useful in the rational design of artificial proteins and nucleotides. We explore halogen-bonded DNA base pairs containing modified guanine, cytosine, adenine and thymine nucleosides. The structures and stabilities of the halogenated systems are compared to the normal hydrogen bonded base pairs. In most cases, energetically stable, coplanar structures are identified. In the most favorable cases, halogenated base pair stabilities are within 2 kcal mol(-1) of the hydrogen bonded analogues. Among the halogens X = Cl, Br, and I, bromine is best suited for inclusion in these biological systems because it possesses the best combination of polarizability and steric suitability. We find that the most stable structures result from a single substitution of a hydrogen bond for a halogen bond in dA:dT and dG:dC base pairs, which allows 1 or 2 hydrogen bonds, respectively, to complement the halogen bond.     

Chimeric GNA/DNA metal-mediated base pairs

DNA double helices comprising chimeric GNA/DNA metal-mediated base pairs have been synthesized and characterized (GNA = glycol nucleic acid). The possibility to combine different nucleic acid backbones within one metal-mediated base pair expands the applicability of metal-functionalized nucleic acids.     

Symmetry selection in artificial DNA base pairs

We report the results of density functional theory (DFT) studies on the formation of the complex H1--Cu2+-H1- consisting of two deprotonated hydroxypyridone ligands (H1-) and a Cu2+ ion. We compare the total energies of three possible structures with different symmetries and show that the structure with plane reflection symmetry has the lowest energy. The electronic structure of the periodic extended DNA-like double helix consisting of stacked H1--Cu2+-H1- units is then calculated within the density functional method, and the double helix is found to be an insulating ferromagnet.     

Electronic properties of metal-modified DNA base pairs

The electronic properties of several metal-modified Watson-Crick guanine-cytosine base pairs are investigated by means of first-principle density functional theory calculations. Focus is placed on a new structure recently proposed as a plausible model for building an antiparallel duplex with Zn-guanine-cytosine pairs, but we also inspect several other conformations and the incorporation of Ag and Cu ions. We analyze the effects induced by the incorporation of one metal cation per base pair by comparing the structures and the electronic properties of the metalated pairs to those of the natural guanine-cytosine pair, particularly for what concerns the modifications of energy levels and charge density distributions of the frontier orbitals. Our results reveal the establishment of covalent bonding between the metal cation and the nucleobases, identified in the presence of hybrid metal-guanine and metal-cytosine orbitals. Attachment of the cation can occur either at the N1 or the N7 site of guanine and is compatible with altering or not altering the H-bond pattern of the natural pair. Cu(II) strongly contributes to the hybridization of the orbitals around the band gap, whereas Ag(I) and Zn(II) give hybrid states farther from the band gap. Most metalated pairs have smaller band gaps than the natural guanine-cytosine pair. The band gap shrinking along with the metal-base coupling suggests interesting consequences for electron transfer through DNA double helices.     

Proton transitions in the hydrogen bonds of the DNA base pairs

The energy levels and wavefunctions of the protons of the hydrogen bonds in DNA base pairs are numerically calculated for a series of adiabatic potential curves. The phenomenon of the so-called proton tunnelling is discussed. The radiative proton transition probabilities are calculated and a comparison with the radiationless ones is made. The relative proton transition probabilities accompanying the electron excitation and de-excitation of the DNA base pairs are evaluated.     

Dynamic behavior of DNA base pairs containing 8-oxoguanine

The process by which DNA repair enzymes recognize and selectively excise damaged bases in duplex DNA is fundamental to our mechanistic understanding of these critical biological reactions. 8-Oxoguanine (8-oxoG) is the most common form of oxidative DNA damage; unrepaired, this lesion generates a G:C-->T:A mutation. Central to the recognition and repair of DNA damage is base extrusion, a process in which the damaged base lesion or, in some cases, its partner disengages from the helix and is bound to the enzyme's active site where base excision takes place. The conformation adopted by 8-oxoG in duplex DNA is affected by the base positioned opposite this lesion; conformational changes may also take place when the damaged base binds to its cognate repair enzyme. We performed unrestrained molecular dynamics simulations for several 13-mer DNA duplexes. Oligomers containing G:C and 8oxoG:C pairs adopted Watson-Crick geometries in stable B-form duplexes; 8oxoG showed increased local and global flexibility and a reduced barrier to base extrusion. Duplexes containing the G:A mismatch showed much larger structural fluctuations and failed to adopt a well-defined structure. For the 8oxoG:A mismatch that is recognized by the DNA glycosylase MutY, the damaged nucleoside underwent spontaneous and reproducible anti-->syn transitions. The syn conformation is thermodynamically preferred. Steric hindrance and unfavorable electrostatics associated with the 8oxoG O8 atom in the anti conformation were the major driving forces for this transition. Transition events follow two qualitatively different pathways. The overall anti-->syn transition rate and relative probability of the two transition paths were dependent on local sequence context. These simulations indicate that both the dynamic and equilibrium behavior of the duplex change as a result of oxidation; these differences may provide valuable new insight into the selective action of enzymes on damaged DNA.     

MercuryII-mediated formation of thymine-HgII-thymine base pairs in DNA duplexes

The very specific binding of the HgII ion unexpectedly and significantly stabilizes naturally occurring thymine-thymine base mispairing in DNA duplexes. Following this finding, we prepared DNA duplexes containing metal-mediated base pairs at the desired sites, as well as novel double helical architectures consisting only of thymine-HgII-thymine pairs.     

Some comments on H-bond dynamics in DNA base pairs

It is advocated that the H -bond patterns of the standard C –G and A –T base pairs have an evolutionary advantage over any other H -bond scheme accommodated within the Watson–Crick-type geometry. A suggested proof of the statement is given by the Longuet–Higgins' sign-reversing loop argument. The present analysis indicates a close relation with self-organizational principles. © 1993 John Wiley & Sons, Inc.     

Characterizing the strength of individual hydrogen bonds in DNA base pairs

The energies of individual hydrogen bonds (H-bonds) in A-T and G-C Watson-Crick base pairs were calculated according to the natural bond orbital (NBO) analysis of intermolecular interactions. The extent to which individual H-bonds are helpful in holding the two base pairs together was previously investigated quantitatively by a few different approaches, and the results of the present and previous estimations were compared. The method was validated by the determination of the H-bond strength changes in A-T and G-C pairs upon the substitution of the monomer (base) by two cationic substituents; the systems for which the changes were previously anticipated based on the modifications of the H-bonds' distances.     

The molecular electrostatic potentials of the complementary base pairs of DNA

The perturbations in the molecular electrostatic potentials of the bases of the nucleic acids, brought about by hydrogen-bonding into complementary pairs are evaluated by a superposition procedure.     

Theoretical study of proton transfers between base pairs of DNA

Single and multiple proton transfers between the bases guanine and cytosine and between adenine and thymine are studied using the LCAO SCF all-electron PRDDO method. Single proton transfers are found to lead to single-well potentials while double transfers are characterized by double-well potentials.     

DNA--metal base pairs

Recent developments show encouraging results for the use of DNA as a construction material for nanometer-sized objects. Today, however, DNA-based molecular nanoarchitectures are constructed with mainly unmodified or at best end-modified oligonucleotides, thus shifting the development of functionalized DNA structures into the limelight. One of most recent developments in this direction is the substitution of the canonical Watson-Crick base pairs by metal complexes. In this way "metal-base pairs" are created, which could potentially impart magnetic or conductive properties to DNA-based nanostructures. This review summarizes research which started almost 45 years ago with the investigation of how metal ions interact with unmodified DNA and which recently culminated in the development of artificial ligand-like nucleobases so far able to coordinate up to ten metal ions inside a single DNA duplex in a programmable fashion.     

Perturbation theory analysis for electronic response of DNA base pairs

The electronic responses of duplex B-DNA sequences are investigated using perturbation theory analyses. The electronic polarizability and effective mass are computed for base pair doublets and triplets and the electronic structures are calculated according to density functional theory. High polarizability and a light effective mass are obtained in a sequence such as 5′-GGG-3′. The results indicate that the concentration of GC base pairs causes a high response of the electronic states, and molecular orbitals that are very responsive to the electric field tend to be reactive with other orbitals or conducting hole carriers. Furthermore, the interaction between the electronic states and a positively charged wavepacket is discussed, assuming hole injection in the DNA sequences. The sequence of 5′-GGG-3′ responds sensitively to the external hole approach, which is presumably injected to a guanine site.     

Metal ion-binding properties of DNA duplexes containing thiopyrimidine base pairs

Thiopyrimidine pairs in DNA duplexes were unexpectedly largely stabilized by complexation with two equivalents of Ag(I) ions and their binding properties were evaluated. The metal ion-binding properties of the thiopyrimidine base pairs differed significantly from those of unpaired bases.     

Ultrafast vibrational dynamics of adenine-thymine base pairs in DNA oligomers

N-H stretching excitations of DNA oligomers containing 23 alternating adenine-thymine base pairs are studied in femtosecond two-color pump-probe experiments. For a DNA film in a zero relative humidity atmosphere, transient vibrational spectra and their time evolution up to 10 ps demonstrate negligible spectral diffusion and allow for discerning different N-H stretching bands and the O-H stretching absorption of residual water molecules. Lifetimes on the order of 0.5 ps are found for both N-H and O-H stretching modes. The time-dependent pump-probe anisotropies of the different N-H excitations point to a pronounced coupling among them, whereas the O-H stretching anisotropy remains essentially constant.