The influence of external electric fields on proton transfer tautomerism in the guanine-cytosine base pair

Alexander Gheorghiu, Peter V. Coveney, Alya A. Arabi

Research output: Contribution to journalArticlepeer-review

10 Citations (Scopus)


The Watson-Crick base pair proton transfer tautomers would be widely considered as a source of spontaneous mutations in DNA replication if not for their short lifetimes and thermodynamic instability. This work investigates the effects external electric fields have on the stability of the guanine-cytosine proton transfer tautomers within a realistic strand of aqueous DNA using a combination of ensemble-based classical molecular dynamics (MD) coupled to quantum mechanics/molecular mechanics (QM/MM). Performing an ensemble of calculations accounts for the stochastic aspects of the simulations while allowing for easier identification of systematic errors. The methodology applied in this work has previously been shown to estimate base pair proton transfer rate coefficients that are in good agreement with recent experimental data. A range of electric fields in the order of 104to 109V m−1is investigated based on their real-life medicinal applications which include gene therapy and cancer treatments. The MD trajectories confirm that electric fields up to 1.00 × 109V m−1have a negligible influence on the structure of the base pairs within DNA. The QM/MM results show that the application of large external electric fields (1.00 × 109V m−1) parallel to the hydrogen bonds increases the thermodynamic population of the tautomers by up to one order of magnitude; moreover, the lifetimes of the tautomers remain insignificant when compared to the timescale of DNA replication.

Original languageEnglish
Pages (from-to)6252-6265
Number of pages14
JournalPhysical Chemistry Chemical Physics
Issue number10
Publication statusPublished - Mar 14 2021

ASJC Scopus subject areas

  • General Physics and Astronomy
  • Physical and Theoretical Chemistry


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