Fluctuations in the DNA double helix: A critical review

Phys Life Rev. 2014 Jun;11(2):153-70. doi: 10.1016/j.plrev.2014.01.005. Epub 2014 Jan 13.

Abstract

A critical overview of the extensive literature on fluctuations in the DNA double helix is presented. Both theory and experiment are comprehensively reviewed and analyzed. Fluctuations, which open up the DNA double helix making bases accessible for hydrogen exchange and chemical modification, are the main focus of the review. Theoretical descriptions of the DNA fluctuations are discussed with special emphasis on most popular among them: the nonlinear-dynamic Peyrard-Bishop-Dauxois (PBD) model and the empirical two-state (or helix-coil) model. The experimental data on the issue are comprehensibly overviewed in the historical retrospective with main emphasis on the hydrogen exchange data and formaldehyde kinetics. The theoretical descriptions are critically evaluated from the viewpoint of their applicability to describe DNA in water environment and from the viewpoint of agreement of their predictions with the reliable experimental data. The presented analysis makes it possible to conclude that, while the two-state model is most adequate from theoretical viewpoint and its predictions, based on an empirical parametrization, agree with experimental data very well, the PBD model is inapplicable to DNA in water from theoretical viewpoint on one hand and it makes predictions totally incompatible with reliable experimental data on the other. In particular, it is argued that any oscillation movements of nucleotides, assumed by the PBD model, are severely damped in water, that no "bubbles", which the PBD model predicts, exist in reality in linear DNA well below the melting range and the lifetime of an open state in DNA is actually 5 orders of magnitude longer than the value predicted by the PBD model.

Keywords: DNA biophysics; Double helix breathing; Formaldehyde method; Helix-coil model; Hydrogen exchange method; Peyrard–Bishop–Dauxois model.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • DNA / chemistry*
  • DNA / metabolism
  • Kinetics
  • Models, Molecular

Substances

  • DNA