This Article Full Text Full Text (PDF) Supplemental File All Versions of this Article: biophysj.104.046912v1 88/3/1684    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Harris, S. A. Articles by Laughton, C. A. Search for Related Content PubMed PubMed Citation Articles by Harris, S. A. Articles by Laughton, C. A.

Molecular Dynamics Simulations of Duplex Stretching Reveal the Importance of Entropy in Determining the Biomechanical Properties of DNA

Sarah A. Harris ^*, Zara A. Sands  and Charles A. Laughton 

^* Department of Physics and Astronomy, University College London, London WC1E 6BT, United Kingdom; and School of Pharmacy, University of Nottingham, Nottingham NG7 2RD, United Kingdom

Correspondence: Address reprint requests to Charles A. Laughton, Centre for Biomolecular Sciences, University of Nottingham, Nottingham NG7 2RD, UK. Tel.: 44-155-951-3405; Fax: 44-155-951-3412; E-mail: charles.laughton{at}nottingham.ac.uk.

Advances in nanomanipulation techniques have made it possible to measure the response of an individual biomolecule to a force applied in the laboratory. Experiments that stretch a single molecule of duplex DNA have been difficult to interpret theoretically, particularly as the major changes in molecular structure caused by the force cannot be measured. In principle, computer simulation can calculate these conformational changes in atomic level detail, but to date such studies have failed to reproduce the experimental data due to the computational expense of the calculations. Here we show that a combination of molecular modeling and statistical physics can be used successfully to understand the stretching behavior of DNA. Our simulations provide new information about the dynamics of DNA denaturation under force in atomic level detail and also show the importance of entropy in determining biomechanical properties in general.

This article has been cited by other articles:

				C. Mura and J. A. McCammon Molecular dynamics of a {kappa}B DNA element: base flipping via cross-strand intercalative stacking in a microsecond-scale simulation Nucleic Acids Res., September 1, 2008; 36(15): 4941 - 4955. [Abstract] [Full Text] [PDF]

				L. Shokri, M. J. McCauley, I. Rouzina, and M. C. Williams DNA Overstretching in the Presence of Glyoxal: Structural Evidence of Force-Induced DNA Melting Biophys. J., August 1, 2008; 95(3): 1248 - 1255. [Abstract] [Full Text] [PDF]

				P. J. in 't Veld and M. J. Stevens Simulation of the Mechanical Strength of a Single Collagen Molecule Biophys. J., July 1, 2008; 95(1): 33 - 39. [Abstract] [Full Text] [PDF]

				C. H. Albrecht, G. Neuert, R. A. Lugmaier, and H. E. Gaub Molecular Force Balance Measurements Reveal that Double-Stranded DNA Unbinds Under Force in Rate-Dependent Pathways Biophys. J., June 15, 2008; 94(12): 4766 - 4774. [Abstract] [Full Text] [PDF]

				S. Whitelam, S. Pronk, and P. L. Geissler There and (Slowly) Back Again: Entropy-Driven Hysteresis in a Model of DNA Overstretching Biophys. J., April 1, 2008; 94(7): 2452 - 2469. [Abstract] [Full Text] [PDF]

				S. A. Harris, C. A. Laughton, and T. B. Liverpool Mapping the phase diagram of the writhe of DNA nanocircles using atomistic molecular dynamics simulations Nucleic Acids Res., January 17, 2008; 36(1): 21 - 29. [Abstract] [Full Text] [PDF]

				J. B. Heng, A. Aksimentiev, C. Ho, P. Marks, Y. V. Grinkova, S. Sligar, K. Schulten, and G. Timp The Electromechanics of DNA in a Synthetic Nanopore Biophys. J., February 1, 2006; 90(3): 1098 - 1106. [Abstract] [Full Text] [PDF]

				S. Piana Structure and energy of a DNA dodecamer under tensile load Nucleic Acids Res., December 14, 2005; 33(22): 7029 - 7038. [Abstract] [Full Text] [PDF]