Theoretical study of a new DNA structure: the antiparallel Hoogsteen duplex

J Am Chem Soc. 2003 Nov 26;125(47):14603-12. doi: 10.1021/ja035918f.

Abstract

The structure of a new form of duplex DNA, the antiparallel Hoogsteen duplex, is studied in polyd(AT) sequences by means of state-of-the-art molecular dynamics simulations in aqueous solution. The structure, which was found to be stable in all of the simulations, has many similarities with the standard Watson-Crick duplex in terms of general structure, flexibility, and molecular recognition patterns. Accurate MM-PB/SA (and MM-GB/SA) analysis shows that the new structure has an effective energy similar to that of the B-type duplex, while it is slightly disfavored by intramolecular entropic considerations. Overall, MD simulations strongly suggest that the antiparallel Hoogsteen duplex is an accessible structure for a polyd(AT) sequence, which might compete under proper experimental conditions with normal B-DNA. MD simulations also suggest that chimeras containing Watson-Crick duplex and Hoogsteen antiparallel helices might coexist in a common structure, but with the differential characteristics of both type of structures preserved.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • DNA / chemistry*
  • Models, Molecular
  • Nucleic Acid Conformation
  • Poly dA-dT / chemistry*
  • Solutions
  • Thermodynamics
  • Water / chemistry

Substances

  • Solutions
  • Water
  • Poly dA-dT
  • DNA