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Thermodynamics of 5-bromouracil tautomerisation from first-principles molecular dynamics simulations

Research output: Chapter in Book/Report/Conference proceedingChapter


Leo F. Holroyd, Michael Buehl, Marie-Pierre Gaigeot, Tanja van Mourik

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We modelled the driving force for aqueous keto-to-enol tautomerisation of 5-bromouracil, a mutagenic thymine analogue, by first-principles molecular dynamics simulations with thermodynamic integration. Using interatomic distance constraints to model the water-assisted (de)protonation of 5-bromouracil in a periodic water box, we show that the free energy for its enolisation is lower than that of the parent compound, uracil, by around 3.0 kcal/mol (BLYP-D2 level), enough to significantly alter the relative tautomeric ratios. Assuming the energetic difference also holds in the cell, this finding is evidence for the “rare tautomer” hypothesis of 5-bromouracil mutagenicity (and, possibly, that of other base analogues).


Original languageEnglish
Title of host publicationQuantum Systems in Physics, Chemistry and Biology - Theory, Interpretation, and Results
EditorsSamantha Jenkins, Steven Kirk, Jean Maruani, Erkki Brandas
PublisherAcademic Press
ISBN (Print)9780128160848
Publication statusPublished - 1 Jan 2019

Publication series

NameAdvances of Quantum Chemistry
PublisherAcademic Press
ISSN (Print)0065-3276

    Research areas

  • Density functional theory, Nucleobases, Solvation effects, Mutagenesis, CPMD, Bromouracil

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