Ab initio base-pairing energies of an oxidized thymine product, 5-formyluracil, with standard DNA bases at the BSSE-free DFT and MP2 theory levels

Org Biomol Chem. 2007 May 21;5(10):1554-8. doi: 10.1039/b702755a. Epub 2007 Apr 17.

Abstract

Oxidation of the thymine methyl group produces two stable products, non-mutagenic 5-hydroxymethyluracil and highly mutagenic 5-formyluracil. We have calculated the interaction energy of base-pair formation involving 5-formyluracil bound to the natural DNA bases adenine (A), cytosine (C), guanine (G), and thymine (T), and discuss the effects of the 5-formyl group with respect to similar base-pairs containing uracil, 5-hydroxyuracil, thymine (5-methyluracil), and 5-hydroxycytosine. The interaction geometries and energies were calculated four ways: (a) using density functional theory (DFT) without basis set super-position error (BSSE) corrections, (b) using DFT with BSSE correction of geometries and energies, (c) using Møller-Plesset second order perturbation theory (MP2) without BSSE correction, and (d) using MP2 with BSSE geometry and energy correction. All calculations used the 6-311G(d,p) basis set. Notably, we find that the A:5-formyluracil base-pair is more stable than the precursor A:T base-pair. The relative order of base-pair stabilities is A:5-Fo-U > G:5-Fo-U > C:5-Fo-U > T:5-Fo-U.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Pairing*
  • Calibration
  • DNA / chemistry*
  • Hydrogen Bonding
  • Models, Chemical
  • Models, Theoretical
  • Mutagens*
  • Nucleic Acid Conformation
  • Oxygen / chemistry
  • Software
  • Thermodynamics
  • Thymidine / chemistry*
  • Thymine / chemistry
  • Uracil / analogs & derivatives*
  • Uracil / chemistry
  • Uracil / pharmacology

Substances

  • Mutagens
  • 5-formyluracil
  • Uracil
  • DNA
  • Thymine
  • Oxygen
  • Thymidine