Atomistic understanding of the C·T mismatched DNA base pair tautomerization via the DPT: QM and QTAIM computational approaches

Brovarets’, Ol’ha O.; Hovorun, Dmytro М.

doi:10.1002/jcc.23412

Cited by 55 publications

(49 citation statements)

References 95 publications

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“…This article, which is a logical extension of the previous works on a kindred topic, is devoted to the finding of the new physicochemical mechanisms of the DNA bases mutagenic tautomerization. An entry point of this article is to find out whether the DPT tautomerization of the long A·G Watson–Crick DNA base mispair, which is considered in the literature as the purine–pyrimidine transversion inducing point mutations in DNA, produces A* and G* mutagenic tautomers at its dissociation in the base‐pair recognition pocket of the DNA polymerase.…”

Section: Introductionmentioning

confidence: 98%

“…A thorough analysis of the literature shows that these issues are now intensively studied and this problem is still far from its final solution. In particular, we showed that the tautomerization as of the A·T and G·C Watson–Crick DNA base pairs, so of the short C·T Watson–Crick DNA base pair via the double proton transfer (DPT) along the intermolecular H‐bonds (so‐called Löwdin's model) does not generate mutagenic tautomers of the DNA bases, as the effect of their quantum protection against mutagenic tautomerization takes place in these structures. The same effect hinders the mutagenic tautomerization of the DNA bases by the DNA‐binding proteins, that are contained in the replisome .…”

Section: Introductionmentioning

confidence: 99%

“…The А*·G* base mispair, formed as a result of the А·G → А*·G* tautomerization via the DPT, was found to be dynamically unstable structure, because the zero‐point energy of the corresponding vibrational mode, which frequency becomes imaginary at the TS А·G ↔ А*·G* , greatly exceeds the value of the reverse barrier of the A·G → A*·G* tautomerization. It should be noted that the value of the Gibbs free energy of activation for the reverse reaction of the A·G → A*·G* tautomerization is negative at all levels of QM theory.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Is the DPT tautomerization of the long A·G Watson–Crick DNA base mispair a source of the adenine and guanine mutagenic tautomers? A QM and QTAIM response to the biologically important question

2013

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Herein, we first address the question posed in the title by establishing the tautomerization trajectory via the double proton transfer of the adenine·guanine (A·G) DNA base mispair formed by the canonical tautomers of the A and G bases into the A*·G* DNA base mispair, involving mutagenic tautomers, with the use of the quantum-mechanical calculations and quantum theory of atoms in molecules (QTAIM). It was detected that the A·G ↔ A*·G* tautomerization proceeds through the asynchronous concerted mechanism. It was revealed that the A·G base mispair is stabilized by the N6H···O6 (5.68) and N1H···N1 (6.51) hydrogen bonds (H-bonds) and the N2H···HC2 dihydrogen bond (DH-bond) (0.68 kcal·mol(-1) ), whereas the A*·G* base mispair-by the O6H···N6 (10.88), N1H···N1 (7.01) and C2H···N2 H-bonds (0.42 kcal·mol(-1) ). The N2H···HC2 DH-bond smoothly and without bifurcation transforms into the C2H···N2 H-bond at the IRC = -10.07 Bohr in the course of the A·G ↔ A*·G* tautomerization. Using the sweeps of the energies of the intermolecular H-bonds, it was observed that the N6H···O6 H-bond is anticooperative to the two others-N1H···N1 and N2H···HC2 in the A·G base mispair, while the latters are significantly cooperative, mutually strengthening each other. In opposite, all three O6H···N6, N1H···N1, and C2H···N2 H-bonds are cooperative in the A*·G* base mispair. All in all, we established the dynamical instability of the А*·G* base mispair with a short lifetime (4.83·10(-14) s), enabling it not to be deemed feasible source of the A* and G* mutagenic tautomers of the DNA bases. The small lifetime of the А*·G* base mispair is predetermined by the negative value of the Gibbs free energy for the A*·G* → A·G transition. Moreover, all of the six low-frequency intermolecular vibrations cannot develop during this lifetime that additionally confirms the aforementioned results. Thus, the A*·G* base mispair cannot be considered as a source of the mutagenic tautomers of the DNA bases, as the A·G base mispair dissociates during DNA replication exceptionally into the A and G monomers in the canonical tautomeric form.

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Section: Introductionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Is the DPT tautomerization of the long A·G Watson–Crick DNA base mispair a source of the adenine and guanine mutagenic tautomers? A QM and QTAIM response to the biologically important question

2013

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“…Owing to their biological importance, the pyrimidine:pyrimidine mispairs have been extensively studied (36,37) and it has been known for long time that both T:T and C:T pairs have very high binding affinities to the mercury ion (38–41); and, these interactions have been widely investigated and utilized to detect or decontaminate the Hg II pollution in the environment (25,42,43). Besides the crystal structure (33), one solution NMR structure (44) of the 12TT DNA duplex containing two consecutive T–Hg II –T pairs was also reported in 2014; both structures revealed a linear N3–Hg II –N3 interaction between the T:T pair and the Hg II ion (Figure 1A).…”

Section: Introductionmentioning

confidence: 99%

Flexibility and stabilization of Hg^II-mediated C:T and T:T base pairs in DNA duplex

et al. 2016

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Owing to their great potentials in genetic code extension and the development of nucleic acid-based functional nanodevices, DNA duplexes containing HgII-mediated base pairs have been extensively studied during the past 60 years. However, structural basis underlying these base pairs remains poorly understood. Herein, we present five high-resolution crystal structures including one first-time reported C–HgII–T containing duplex, three T–HgII–T containing duplexes and one native duplex containing T–T pair without HgII. Our structures suggest that both C–T and T–T pairs are flexible in interacting with the HgII ion with various binding modes including N3–HgII–N3, N4–HgII–N3, O2–HgII–N3 and N3–HgII–O4. Our studies also reveal that the overall conformations of the C–HgII–T and T–HgII–T pairs are affected by their neighboring residues via the interactions with the solvent molecules or other metal ions, such as SrII. These results provide detailed insights into the interactions between HgII and nucleobases and the structural basis for the rational design of C–HgII–T or T–HgII–T containing DNA nanodevices in the future.

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“…mono-H 2 ImP-AQ, mono-H 2 PyP-AQ, mono-H 2 PzP-AQ, bis-H 2 ImP-AQ, bis-H 2 PyP-AQ, bis-H 2 PzP-AQ, tris-H 2 ImP-AQ, tris-H 2 PyP-AQ, and tris-H 2 PzP-AQ. Each ligand structure was built with the help of GaussView and then geometry optimized using Gaussian09 on 6-31G* basis set using the Becke three-parameter Lee-Yang-Parr (B3LYP) hybrid density functional theory that has been well proven in the quantum-chemical studies of the H-bonded DNA base pairs Samijlenko, Yurenko, Stepanyugin, & Hovorun, 2010;Brovarets & Hovorun, 2013a;Brovarets & Hovorun, 2013b;Brovarets, Zhurakivsky, & Hovorun, 2013;Brovarets, Zhurakivsky, & Hovorun, 2015;Brovarets, Yurenko, Dubey, & Hovorun, 2012;Brovarets, Yurenko, & Hovorun, 2013;Ponomareva, Yurenko, Zhurakivsky, van Mourik, & Hovorun, 2013). The structure with the lowest energy conformation was selected and then prepared for further docking study with maximum torsion with the AutoDockTools (AutoDockTools, 2007).…”

Section: Macromolecule Preparationmentioning

confidence: 99%

Molecular docking and dynamics simulations on the interaction of cationic porphyrin–anthraquinone hybrids with DNA G-quadruplexes

Arba

Kartasasmita

Tjahjono

2015

Journal of Biomolecular Structure and Dynamics

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A series of cationic porphyrin-anthraquinone hybrids bearing either pyridine, imidazole, or pyrazole rings at the meso-positions have been investigated for their interaction with DNA G-quadruplexes by employing molecular docking and molecular dynamics simulations. Three types of DNA G-quadruplexes were utilized, which comprise parallel, antiparallel, and mixed hybrid topologies. The porphyrin hybrids have a preference to bind with parallel and mixed hybrid structures compared to the antiparallel structure. This preference arises from the end stacking of porphyrin moiety following G-stem and loop binding of anthraquinone tail, which is not found in the antiparallel due to the presence of diagonal and lateral loops that crowd the G-quartet. The binding to the antiparallel, instead, occurred with poorer affinity through both the loop and wide groove. All sites of porphyrin binding were confirmed by 6 ns molecular dynamics simulation, as well as by the negative value of the total binding free energies that were calculated using the MMPBSA method. Free energy analysis shows that the favorable contribution came from the electrostatic term, which supposedly originated from the interaction of either cationic pyridinium, pyrazole, or imidazole groups and the anionic phosphate backbone, and also from the van der Waals energy, which primarily contributed through end stacking interaction.

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Atomistic understanding of the C·T mismatched DNA base pair tautomerization via the DPT: QM and QTAIM computational approaches

Cited by 55 publications

References 95 publications

Is the DPT tautomerization of the long A·G Watson–Crick DNA base mispair a source of the adenine and guanine mutagenic tautomers? A QM and QTAIM response to the biologically important question

Is the DPT tautomerization of the long A·G Watson–Crick DNA base mispair a source of the adenine and guanine mutagenic tautomers? A QM and QTAIM response to the biologically important question

Flexibility and stabilization of Hg^II-mediated C:T and T:T base pairs in DNA duplex

Molecular docking and dynamics simulations on the interaction of cationic porphyrin–anthraquinone hybrids with DNA G-quadruplexes

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Atomistic understanding of the C·T mismatched DNA base pair tautomerization via the DPT: QM and QTAIM computational approaches

Cited by 55 publications

References 95 publications

Is the DPT tautomerization of the long A·G Watson–Crick DNA base mispair a source of the adenine and guanine mutagenic tautomers? A QM and QTAIM response to the biologically important question

Is the DPT tautomerization of the long A·G Watson–Crick DNA base mispair a source of the adenine and guanine mutagenic tautomers? A QM and QTAIM response to the biologically important question

Flexibility and stabilization of HgII-mediated C:T and T:T base pairs in DNA duplex

Molecular docking and dynamics simulations on the interaction of cationic porphyrin–anthraquinone hybrids with DNA G-quadruplexes

Contact Info

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Resources

About

Flexibility and stabilization of Hg^II-mediated C:T and T:T base pairs in DNA duplex