Theoretical study of large conformational transitions in DNA: the B<-->A conformational change in water and ethanol/water

Nucleic Acids Res. 2007;35(10):3330-8. doi: 10.1093/nar/gkl1135. Epub 2007 Apr 25.

Abstract

We explore here the possibility of determining theoretically the free energy change associated with large conformational transitions in DNA, like the solvent-induced B<-->A conformational change. We find that a combination of targeted molecular dynamics (tMD) and the weighted histogram analysis method (WHAM) can be used to trace this transition in both water and ethanol/water mixture. The pathway of the transition in the A-->B direction mirrors the B-->A pathway, and is dominated by two processes that occur somewhat independently: local changes in sugar puckering and global rearrangements (particularly twist and roll) in the structure. The B-->A transition is found to be a quasi-harmonic process, which follows closely the first spontaneous deformation mode of B-DNA, showing that a physiologically-relevant deformation is in coded in the flexibility pattern of DNA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Computer Simulation
  • DNA / chemistry*
  • DNA, A-Form / chemistry*
  • Ethanol / chemistry
  • Models, Molecular*
  • Nucleic Acid Conformation
  • Solvents / chemistry
  • Water / chemistry

Substances

  • DNA, A-Form
  • Solvents
  • Water
  • Ethanol
  • DNA