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Cited by 38DNA and Nucleic Acid ChemistryRNA and protein synthesis mechanismsChemical Reaction Mechanisms

Proton Transfer in Guanine-Cytosine Base Pairs in B-DNA

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Soler-Polo, Diego, Mendieta-Moreno, Jesús I., Trabada, Daniel G., Mendieta, Jesús, Ortega, José·2019·Journal of Chemical Theory and Computation
DOI 10.1021/acs.jctc.9b00757
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Abstract

A double proton transfer reaction in a guanine-cytosine (GC) base pair has been proposed as a possible mechanism for rare tautomer (G*C*) formation and thus a source of spontaneous mutations. We analyze this system with free energy calculations based on extensive Quantum Mechanics/Molecular Mechanics simulations to properly consider the influence of the DNA biomolecular environment. We find that, although the G*C* rare tautomer is metastable in the gas phase, it is completely unstable in the conditions found in cells. Thus, our calculations show that a double proton reaction cannot be the source of spontaneous point mutations. We have also analyzed the intrabase H transfer reactions in guanine. Our results show that the DNA environment gives rise to a large free energy difference between the rare and canonical tautomers. These results show the key role of the DNA biological environment for the stability of the genetic code.

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  • The tautomeric state A*-T* is extremely unstable, with a fleetingly short lifetime, and therefore not as likely to play a role in mutagenesis.

    “Our decision to study G-C rather than A-T is because the tautomeric state, A*-T*, is extremely unstable, with a fleetingly short lifetime, and therefore not as likely to play a role in mutagenesis 4,5,7,13 .”

    From An open quantum systems approach to proton tunnelling in DNA (2022) · cites this paper as [13]

    The paper’s discussion of A*T* (indexed under Abstract; page not given) says gas-phase studies find no local minimum for it, or only a very shallow one, and concludes that double proton transfer does not contribute to A* or T* rare tautomers. That supports the instability and reduced mutagenic relevance attributed to the source, but the paper does not establish a fleetingly short A*T* lifetime or test its stability in B-DNA. (LLM, conf=0.83)

    Experimental — accuracy not yet measured

  • Computational studies suggest that the monomeric form of the tautomers are stable and extremely long-lived due to their prohibitively large reaction barriers.

    “On the other hand, computational studies suggest that the monomeric form of the tautomers are stable and extremely longlived due to their prohibitively large reaction barriers 4,13,48,49 .”

    From An open quantum systems approach to proton tunnelling in DNA (2022) · cites this paper as [13]

    The discussion of Figure 6 (indexed under Abstract; page unavailable) reports a very large, approximately 48 kcal/mol barrier between isolated guanine and its rare tautomer, consistent with a long-lived monomeric guanine tautomer. It does not establish that monomeric tautomers generally are extremely long-lived; the paper also reports a much smaller reverse barrier for the gas-phase G*C* base pair. (LLM, conf=0.85)

    Experimental — accuracy not yet measured

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Cited by

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Authors
Soler-Polo, D., Mendieta-Moreno, J. I., Trabada, D. G., Mendieta, J., & Ortega, J.
Affiliations
  • Departamento de Física Teórica de la Materia Condensada and Condensed Matter Physics Center (IFIMAC), Facultad de Ciencias, Universidad Autónoma de Madrid, E-28049 Madrid, Spain
  • Universidad Autónoma de Madrid (ES)
  • Universidad Francisco de Vitoria (ES)
Corresponding author
Ortega, José
ORCID
Venue
Journal of Chemical Theory and Computation
Publisher
American Chemical Society (ACS)
Published
2019-10-30
Volume
15
Issue
12
Pages
6984-6991
ISSN
  • 1549-9618 (ISSN-L)
  • 1549-9626
DOI
10.1021/acs.jctc.9b00757
OpenAlex
W2982461944
Cited by
38
References
3
Citations by year
2026: 2 · 2025: 6 · 2024: 6 · 2023: 7 · 2022: 10 · 2021: 5 · 2020: 2
FWCI
1.41
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Chemical Theory and Computation (publishedVersion)
  • PubMed (publishedVersion)
  • Hispana (acceptedVersion)
  • LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (submittedVersion, other-oa)
  • Biblos-e Archivo (Universidad Autónoma de Madrid) (submittedVersion, public-domain)
  • Deposito Digital UFV (Francisco de Vitoria University) (submittedVersion, cc-by-nc-nd)
Funders
Secretar?a de Estado de Investigaci?n, Desarrollo e Innovaci?n (MDM-2014-0377, MAT2017-88258-R)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA and Nucleic Acid Chemistry
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
  • Physical Sciences › Chemistry › Organic Chemistry › Chemical Reaction Mechanisms
Keywords
proton transfer, guanine-cytosine base pair, B-DNA, spontaneous mutation, tautomer stability, free energy calculation, quantum mechanics/molecular mechanics
MeSH terms
Cytosine, Guanine, Protons, Quantum Theory, Base Pairing, DNA, B-Form

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