Understanding the mechanical properties that guide the flexibility of DNA is important, as DNA must bend and/or stretch in order to function biologically. In addition, there is interest in using DNA as a nanoscopic length and force standard. Over the past decade and a half single molecule experiments have been developed which can measure the response of DNA to applied forces. While these experiments have provided valuable insights into the stability of DNA, it is often not possible to relate the experimental data to specific structural changes. In a specific example of this, recent experimental work has shown that above a certain loading rate double-stranded DNA is more stable when stretched from the 3'-3' termini than when stretched from the 5'-5' termini. The structural basis for this behavior is not well understood, and indeed early calculations comparing the energetics of these two ways of stretching DNA had indicated the opposite may be true. For this study we have used molecular dynamics simulations combined with umbrella sampling to study the kinetic behavior and stability of a 30 bp double-stranded DNA oligomer during stretching from either the 3'-3' ends or the 5'-5' ends. The results from the umbrella sampling simulations show that at extensions greater than 1.7x the 3'-3' stretched structure is more stable than the 5'-5' stretched structure. A detailed comparison of these highly stretched conformations reveals that when DNA is stretched from the 3' termini it adopts a metastable conformation that maintains a larger number of native hydrogen bonds between base pairs and a higher degree of base stacking. These results demonstrate that 3 -3 stretching and 5 -5 stretching in DNA are fundamentally different processes.
Citation: Journal of Physical Chemistry B
Pub Type: Journals
DNA duplex oligonucleotide, DNA Stretching, Molecular Dynamics, Potential of Mean Force Calculations