Nucleic Acids Research Advance Access originally published online on February 20, 2008
Nucleic Acids Research 2008 36(7):2268-2283; doi:10.1093/nar/gkm1135
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Nucleic Acids Research, 2008, Vol. 36, No. 7 2268-2283
© 2008 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 |
Magnitude and direction of DNA bending induced by screw-axis orientation: influence of sequence, mismatches and abasic sites
1School of Engineering and Science, Jacobs University, Campus Ring 1, D-28759 Bremen, Germany and 2Bioinformatique et RMN structurales, Institut de Biologie et Chimie des Proteines, UMR 5086 CNRS, 7 passage du Vercors, 69367 Lyon, France
*To whom correspondence should be addressed. Tel: +494212003541; Fax: +394212003249; Email: m.zacharias{at}jacobs-university.de
Received July 12, 2007. Revised December 5, 2007. Accepted December 6, 2007.
DNA-bending flexibility is central for its many biological functions. A new bending restraining method for use in molecular mechanics calculations and molecular dynamics simulations was developed. It is based on an average screw rotation axis definition for DNA segments and allows inducing continuous and smooth bending deformations of a DNA oligonucleotide. In addition to controlling the magnitude of induced bending it is also possible to control the bending direction so that the calculation of a complete (2-dimensional) directional DNA-bending map is now possible. The method was applied to several DNA oligonucleotides including A(adenine)-tract containing sequences known to form stable bent structures and to DNA containing mismatches or an abasic site. In case of G:A and C:C mismatches a greater variety of conformations bent in various directions compared to regular B-DNA was found. For comparison, a molecular dynamics implementation of the approach was also applied to calculate the free energy change associated with bending of A-tract containing DNA, including deformations significantly beyond the optimal curvature. Good agreement with available experimental data was obtained offering an atomic level explanation for stable bending of A-tract containing DNA molecules. The DNA-bending persistence length estimated from the explicit solvent simulations is also in good agreement with experiment whereas the adiabatic mapping calculations with a GB solvent model predict a bending rigidity roughly two times larger.