DFT Calculations on the Effect of Solvation on the Tautomeric Reactions for Wobble Gua-Thy and Canonical Gua-Cyt Base-Pairs


To elucidate the reaction mechanism from wobble Guanine-Thymine (wG-T) to tautomeric G-T base-pairs, we investigate its transition state (TS) by density functional theory (DFT) calculations, in vacuum and in water approximated by continuum solvation model. From the comparison of these results, we attempt to elucidate the effect of solvation on the tautomeric reaction for wG-T. In addition, the same DFT calculations are performed for the canonical G-C base-pair, in order to reveal the difference in the activation energy for the reactions involving wG-T and G-C. The obtained TS structures between wG-T and G*-T/G-T* (asterisk is an enol-form of base) are almost the same in vacuum and in water. However, the activation energy is 16.6 and 19.1 kcal/mol in vacuum and in water, respectively, indicating that the effect of solvation enlarges the energy barrier for the reactions from wG-T to G-T*/G*-T. The activation energy for the tautomeric reaction from G-C to G*-C* is also evaluated to be 15.8 and 12.9 kcal/mol in vacuum and in water, respectively. Therefore, it is expected that the tautomeric reaction from wG-T to G*-T/G-T* can occur in vacuum with a similar probability as that from G-C to G*-C*. We furthermore investigate the TS structure for wG-BrU to reveal the effect of the BrU introduction into wG-T. The activation energy is 14.5 and 16.7 kcal/mol in vacuum and in water, respectively. Accordingly, the BrU introduction is found to increase the probability of the tautomeric reaction producing the enol-form G* and T* bases. Because G* prefers to bind to T rather than to C, and T* to G not A, our calculated results reveal that the spontaneous mutation from C to T or from A to G bases is accelerated by the introduction of wG-BrU base-pair.

Share and Cite:

K. Nomura, R. Hoshino, E. Shimizu, Y. Hoshiba, V. Danilov and N. Kurita, "DFT Calculations on the Effect of Solvation on the Tautomeric Reactions for Wobble Gua-Thy and Canonical Gua-Cyt Base-Pairs," Journal of Modern Physics, Vol. 4 No. 3A, 2013, pp. 422-431. doi: 10.4236/jmp.2013.43A059.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] F. H. C. Crick, “The Croonian Lecture, 1966: The Genetic Code,” Proceedings of the Royal Society B, Vol. 167, No. 1009, 1967, pp. 331-347. doi:10.1098/rspb.1967.0031
[2] M. D. Topal and J. R. Fresco, “Complementary Base Pairing and the Origin of Substitution Mutations,” Nature, Vol. 263, 1976, pp. 285-289. doi:10.1038/263285a0
[3] T. A. Early, J. Olmsted III, D. R. Keams and A. G. Lezius, “Base Pairing Structure in the Poly d(G-T) Double Helix: Wobble Base Pairs,” Nucleic Acids Research, Vol. 5, No. 6, 1978, pp. 1955-1970. doi:10.1093/nar/5.6.1955
[4] W. N. Hunter, T. Brown, G. Kneale, N. N. Annad, D. Rabinovich and O. Kennard, “The Structure of Guanosine-Thymidine Mismatches in B-DNA at 2.5-A Resolution,” Journal of Biological Chemistry, Vol. 262, 1987, pp. 9962-9970.
[5] T. Brown, O. Kennard, G. Kneale and D. Rabinovich, “High-resolution Structure of a DNA Helix Containing Mismatched Base Pairs,” Nature, Vol. 315, 1985, pp. 604-606. doi:10.1038/315604a0
[6] P. S. Ho, C. A. Frederick, G. J. Quigley, G. A. van der Marel, J. H. van Boom, A. H.-J. Wang and A. Rich, “G-T Wobble Base-Pairing in Z-DNA at 1.0 A Atomic Resolution: The Crystal Structure of d(CGCGTG),” EMBO Journal, Vol. 4, 1985, pp. 3617-3623.
[7] A. Padermshoke, Y. Katsumoto, R. Masaki and M. Aida, “Thermally Induced Double Proton Transfer in GG and Wobble GT Base-pairs: A Possible Origin of the Mutagenic Guanine,” Chemical Physics Letters, Vol. 457, No. 1-3, 2008, pp. 232-236. doi:10.1016/j.cplett.2008.04.029
[8] O. O. Brovarets and D. M. Hovorun, “Physicochemical Mechanism of the Wobble DNA Base-pairs Gua-Thy and Ade-Cyt Transition into the Mismatched Base-Pairs Gua*-Thy and Ade-Cyt* Formed by the Mutagenic Tautomers,” Ukrainica Bioorganica Acta, Vol. 2, 2009, pp. 12-18.
[9] O. O. Brovarets and D. M. Hovorun, “The New Physicochemical Mechanism of the Mutagenic Action of 5-Bromouracil,” Ukrainica Bioorganica Acta, Vol. 2, 2009, pp. 19-23.
[10] O. O. Brovarets and D. M. Hovorun, “Whether 5-Bromouracile and Its Analogues Produce DNA Point Replication Errors? Results of Quantum-Chemical Analysis,” Bulletin of University of Kyiv Series: Physics & Mathematics, Vol. N2, 2010, pp. 239-242.
[11] K. Nomura, R. Hoshino, Y. Hoshiba, V. I. Danilov and N. Kurita, “Effect of BrU on the Transition Between Wobble Gua-Thy and Tautomeric Gua-Thy Base-pairs: Ab Initio Molecular Orbital Calculations,” IOP Journal of Physics: Conference Series (JPCS), the Proceedings of the AP-IRC 2012, 2013.
[12] M. J. Frisch, et al., “Gaussian09,” Gaussian Inc., Wallingford, 2009.
[13] Y. Zhao and D. G. Truhlar, “The M06 Suite of Density Functionals for Main Group Thermochemistry, Thermo-chemical Kinetics, Noncovalent Interactions, Excited States, and Transition Elements: Two New Functionals and Systematic Testing of Four M06-class Functionals and 12 Other Functionals,” Theoretical Chemical Accounts, Vol. 120, No. 1-3, 2008, pp. 215-241. doi:10.1007/s00214-007-0310-x
[14] C. Peng and H. B. Schlegel, “Combining Synchronous Transit and Quasi-Newton Methods to Find Transition States,” Israel Journal of Chemistry, Vol. 33, 1993, pp. 449-454.
[15] C. Gonzalez and H. B. Schlegel, “An Improved Algorithm for Reaction Path Following,” Journal of Chemical Physics, Vol. 90, No. 4, 1989, pp. 2154-2161. doi:10.1063/1.456010
[16] J. Tomasi, B. Mennucci and E. Cancès, “The IEF Version of the PCM Solvation Method: An Overview of a New Method Addressed to Study Molecular Solutes at the QM Ab Initio Level,” Journal of Molecular Structure (Theochem), Vol. 464, 1999, pp. 211-226.
[17] L. Gorb, Y. Podolyan, P. Dziekonski, W. A. Sokalski and J. Leszczynski, “Double-proton Transfer in Adenine-Thymine and Guanine-Cytosine Base Pairs. A Post Hartree-Fock Ab Initio Study,” Journal of American Chemical Society, Vol. 126, No. 32, 2004, pp. 10119-10129. doi:10.1021/ja049155n

Copyright © 2021 by authors and Scientific Research Publishing Inc.

Creative Commons License

This work and the related PDF file are licensed under a Creative Commons Attribution 4.0 International License.