Jump to main content
Jump to site search

Issue 45, 2009
Previous Article Next Article

Simulation of DNA double-strand dissociation and formation during replica-exchange molecular dynamics simulations

Author affiliations

Abstract

The process of DNA double-strand (dsDNA) formation for a four-base pair (dCGCG)2 model system was studied using umbrella sampling combined with replica-exchange molecular dynamics simulations (REMD) and a generalized Born continuum solvent model. Disruption of dsDNA during the simulations was achieved by stepwise increasing the reference distance in a quadratic restraining potential between the nucleic acid backbone of the two DNA strands. During the reverse simulation (stepwise decrease of the distance starting from completely separated and unfolded single strands) full reformation of a dsDNA in close agreement with B-form geometry was achieved during REMD but not continuous MD simulations. The simulations allowed the calculation of a potential of mean force for the dsDNA formation along the reaction coordinate and were used to characterize intermediate structures. In addition, it was possible to analyze the change of various energetic contributions during disruption and formation of dsDNA that favor or disfavor duplex formation. The calculated free energy change of ∼−3.2 (±1.5) kcal mol−1 and enthalpy change of ∼−37 kcal mol−1 for (dCGCG)2 duplex formation was in good agreement with corresponding experimental values of ∼−3.9 kcal mol−1 and −38.5 kcal mol−1, respectively.

Graphical abstract: Simulation of DNA double-strand dissociation and formation during replica-exchange molecular dynamics simulations

Back to tab navigation

Article information


Submitted
01 Jun 2009
Accepted
06 Aug 2009
First published
15 Sep 2009

Phys. Chem. Chem. Phys., 2009,11, 10589-10595
Article type
Paper

Simulation of DNA double-strand dissociation and formation during replica-exchange molecular dynamics simulations

S. Kannan and M. Zacharias, Phys. Chem. Chem. Phys., 2009, 11, 10589
DOI: 10.1039/B910792B

Social activity

Search articles by author

Spotlight

Advertisements