Nucleic Acids Research Advance Access originally published online on April 20, 2009
Nucleic Acids Research 2009 37(11):3766-3773; doi:10.1093/nar/gkp234
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Nucleic Acids Research, 2009, Vol. 37, No. 11 3766-3773
© 2009 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Computational Biology |
Local and global effects of strong DNA bending induced during molecular dynamics simulations
1Computational Biology, School of Engineering and Science, Jacobs University, Campus Ring 1, D-28759 Bremen, Germany and 2Bioinformatique et RMN structurales, Institut de Biologie et Chimie des Protéines, UMR 5086 CNRS/Université de Lyon, 7 passage du Vercors, 69367 Lyon, France
*To whom correspondence should be addressed. Tel: +33 4 72 72 26 37; Fax: +33 4 72 72 26 04; Email: k.zakrzewska{at}ibcp.fr
Received December 22, 2008. Revised March 26, 2009. Accepted March 27, 2009.
DNA bending plays an important role in many biological processes, but its molecular and energetic details as a function of base sequence remain to be fully understood. Using a recently developed restraint, we have studied the controlled bending of four different B-DNA oligomers using molecular dynamics simulations. Umbrella sampling with the AMBER program and the recent parmbsc0 force field yield free energy curves for bending. Bending 15-base pair oligomers by 90° requires roughly 5 kcal mol–1, while reaching 150° requires of the order of 12 kcal mol–1. Moderate bending occurs mainly through coupled base pair step rolls. Strong bending generally leads to local kinks. The kinks we observe all involve two consecutive base pair steps, with disruption of the central base pair (termed Type II kinks in earlier work). A detailed analysis of each oligomer shows that the free energy of bending only varies quadratically with the bending angle for moderate bending. Beyond this point, in agreement with recent experiments, the variation becomes linear. An harmonic analysis of each base step yields force constants that not only vary with sequence, but also with the degree of bending. Both these observations suggest that DNA is mechanically more complex than simple elastic rod models would imply.