Overstretching of a 30 bp DNA duplex studied with steered molecular dynamics simulation: effects of structural defects on structure and force-extension relation

Eur Phys J E Soft Matter. 2009 Nov;30(3):325-32. doi: 10.1140/epje/i2009-10524-5. Epub 2009 Oct 22.

Abstract

Single-molecule experiments on polymeric DNA show that the molecule can be overstretched at nearly constant force by about 70% beyond its relaxed contour length. In this publication we use steered molecular dynamics (MD) simulation to study the effect of structural defects on force-extension curves and structures at high elongation in a 30 base pair duplex pulled by its torsionally unconstrained 5' -5' ends. The defect-free duplex shows a plateau in the force-extension curve at 120 pN in which large segments with inclined and paired bases ("S-DNA") near both ends of the duplex coexist with a central B-type segment separated from the former by small denaturation bubbles. In the presence of a base mismatch or a nick, force-extension curves are very similar to the ones of the defect-free duplex. For the duplex with a base mismatch, S-type segments with highly inclined base pairs are not observed; rather, the overstretched duplex consists of B-type segments separated by denaturation bubbles. The nicked duplex evolves, via a two-step transition, into a two-domain structure characterized by a large S-type segment coexisting with several short S-type segments which are separated by short denaturation bubbles. Our results suggest that in the presence of nicks the force-extension curve of highly elongated duplex DNA might reflect locally highly inhomogeneous stretching.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Pair Mismatch
  • Base Sequence
  • Biomechanical Phenomena
  • DNA / chemistry*
  • DNA / genetics
  • Molecular Dynamics Simulation*
  • Nucleic Acid Conformation
  • Nucleic Acid Denaturation

Substances

  • DNA