Stacking of the mutagenic DNA base analog 5-bromouracil

Leo F. Holroyd, Tanja van Mourik*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

10 Citations (Scopus)

Abstract

The potential energy surface of the stacked 5-bromouracil/uracil (BrU/U) dimer has been investigated in the gas phase and in solution (water and 1,4-dioxane), modeled by a continuum solvent using the polarizable continuum model. Minima and transition states were optimized using DFT (the M06-2X density functional and the 6-31+G(d) basis set). Six stacked gas-phase BrU/U minima were located: four in the face-to-back orientation and two face-to-face. The global minimum in the gas phase is a face-to-face structure with a twist angle of 60A degrees and a zero-point energy-corrected interaction energy of -10.7 kcal/mol. The BrU/U potential energy surface is geometrically and energetically similar to that of U/U (Hunter and Van Mourik in J Comput Chem 33:2161, 2012). Energy calculations were also performed on experimental geometries of stacked dimers (47 containing BrU stacking with either adenine, cytosine, guanine or thymine and 51 containing thymine also stacking with one of those four bases) taken from DNA structures in the Protein Data Bank. Single-point interaction energies were computed at different levels of theory including MP2, CCSD(T) and DFT using the mPW2PLYP-D double-hybrid functional augmented with an empirical dispersion term, using basis sets ranging from aug-cc-pVDZ to aug-cc-pVQZ. No strong evidence was found for the suggestion that the mutagenicity of BrU is due to enhanced stacking of BrU compared to the corresponding stacked dimers involving thymine.

Original languageEnglish
Article number1431
Number of pages13
JournalTheoretical Chemistry Accounts
Volume133
Issue number2
Early online date14 Dec 2013
DOIs
Publication statusPublished - 2014

Keywords

  • 5-Bromouracil
  • DFT
  • Density functional theory
  • Stacking
  • Dispersion
  • Mutagenicity
  • HYBRID DENSITY FUNCTIONALS
  • TRIPLES CORRECTION T
  • AB-INITIO
  • NONCOVALENT INTERACTIONS
  • MOLECULAR INTERACTIONS
  • ELECTRON CORRELATION
  • AROMATIC STACKING
  • URACIL DIMER
  • DISPERSION
  • ACID

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