Procedure for Selecting Starting Conformations for Energy Minimization of Nucleosides and Nucleotides

2007

Nucleic Acids Research

128

The 2′-deoxyguanosine-3′,5′-diphosphate, 2′-deoxyadenosine-3′,5′-diphosphate, 2′-deoxycytidine-3′,5′-diphosphate and 2′-deoxythymidine-3′,5′-diphosphate systems are the smallest units of a DNA single strand. Exploring these comprehensive subunits with reliable density functional methods enables one to approach reasonable predictions of the properties of DNA single strands. With these models, DNA single strands are found to have a strong tendency to capture low-energy electrons. The vertical attachment energies (VEAs) predicted for 3′,5′-dTDP (0.17 eV) and 3′,5′-dGDP (0.14 eV) indicate that both the thymine-rich and the guanine-rich DNA single strands have the ability to capture electrons. The adiabatic electron affinities (AEAs) of the nucleotides considered here range from 0.22 to 0.52 eV and follow the order 3′,5′-dTDP > 3′,5′-dCDP > 3′,5′-dGDP > 3′,5′-dADP. A substantial increase in the AEA is observed compared to that of the corresponding nucleic acid bases and the corresponding nucleosides. Furthermore, aqueous solution simulations dramatically increase the electron attracting properties of the DNA single strands. The present investigation illustrates that in the gas phase, the excess electron is situated both on the nucleobase and on the phosphate moiety for DNA single strands. However, the distribution of the extra negative charge is uneven. The attached electron favors the base moiety for the pyrimidine, while it prefers the 3′-phosphate subunit for the purine DNA single strands. In contrast, the attached electron is tightly bound to the base fragment for the cytidine, thymidine and adenosine nucleotides, while it almost exclusively resides in the vicinity of the 3′-phosphate group for the guanosine nucleotides due to the solvent effects. The comparatively low vertical detachment energies (VDEs) predicted for 3′,5′-dADP− (0.26 eV) and 3′,5′-dGDP− (0.32 eV) indicate that electron detachment might compete with reactions having high activation barriers such as glycosidic bond breakage. However, the radical anions of the pyrimidine nucleotides with high VDE are expected to be electronically stable. Thus the base-centered radical anions of the pyrimidine nucleotides might be the possible intermediates for DNA single-strand breakage.

Section: Introductionmentioning

confidence: 99%

Electron attachment to DNA single strands: gas phase and aqueous solution

2007

Nucleic Acids Research

128

“…Semiempirical methods were first applied to evaluate the EAs of nucleosides and nucleotides. 58,59 Later, more reliable predictions of the electron affinities of nucleosides, 60 nucleoside pair, 61 and nucleotides 62,63 have been made with the calibrated B3LYP/DZP++ approach. Studies of electron attachment to nucleosides and nucleotides have also led to the elucidation of the mechanisms of chargeinduced strand breaks in DNA.…”

Section: Introductionmentioning

confidence: 99%

“…Efforts toward understanding electron attachment to DNA have been extended to larger DNA units. Semiempirical methods were first applied to evaluate the EAs of nucleosides and nucleotides. , Later, more reliable predictions of the electron affinities of nucleosides, nucleoside pair, and nucleotides , have been made with the calibrated B3LYP/DZP++ approach. Studies of electron attachment to nucleosides and nucleotides have also led to the elucidation of the mechanisms of charge-induced strand breaks in DNA. − Investigations reveal that the formation of a nucleobase-centered radical anion is the key step in either C3‘−O3‘ and C5‘−O5‘ (see Figure for atom numbering) σ bond breakage 62-67 or N1-glycosidic bond rupture in DNA induced by low-energy electrons .…”

Section: Introductionmentioning

confidence: 99%

Understanding Electron Attachment to the DNA Double Helix: The Thymidine Monophosphate−Adenine Pair in the Gas Phase and Aqueous Solution

2006

J. Phys. Chem. B

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.

“…For the nucleosides and nucleotides, semiempirical methods have been applied to evaluate EAs. , Recently, with reliably calibrated B3LYP/DZP++ approaches, a more accurate bracketing of the electron affinities of the 2‘-deoxyribonucleosides has been accomplished . Due to the influence of the 2‘-deoxyribose, the EA ad values for dA, dG, dC, and dT are all positive.…”

Section: Introductionmentioning

confidence: 99%

Structural and Energetic Characterization of a DNA Nucleoside Pair and Its Anion: Deoxyriboadenosine (dA) − Deoxyribothymidine (dT)

2005

J. Phys. Chem. B

The geometries of the DNA nucleoside pairs between 2'-deoxyriboadenosine (dA) and 2'-deoxyribothymidine (dT) and its anion (dAdT-) were fully optimized using carefully calibrated density functional methods. The addition of an electron to dAdT results in remarkable changes to the two hydrogen bonding distances, the H...O distance decreasing by 0.303 angstroms and the N...H distance increasing by 0.229 angstroms. The electron affinity of the dAdT pair was studied to reveal the correct trends of adiabatic electron affinity (EA(ad)) under the influence of the additional components to the individual bases. The consequence of negative charge in terms of structural variations, energetic changes, and charge distribution were explored. The EA(ad) of dAdT is predicted to be positive (0.60 eV), and it exhibits a substantial increase compared with those of the corresponding bases A and T and the nucleic acid base pair AT. The effects of pairing and the addition of the sugar moiety on the EA(ad) are well described as the summation of the individual influences. The influence of the pairing on the EA is comparable to that of the addition of 2-deoxyribose. The excess charge is mainly located on the thyminyl moiety in the anionic dAdT pair. The positive vertical electron affinity (VEA = 0.20 eV) for dAdT suggests that it is able to form a stable anion through electron attachment. A large vertical detachment energy (VDE = 1.14 eV) has been determined for the anionic dAdT nucleoside pair. Therefore, one may expect that the stable anionic dAdT nucleoside pair should be able to undergo the subsequent glycosidic bond cleavage process.