Nucleic Acids Research Advance Access originally published online on March 5, 2009
Nucleic Acids Research 2009 37(7):2405-2410; doi:10.1093/nar/gkp016
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Nucleic Acids Research, 2009, Vol. 37, No. 7 2405-2410
© 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 |
A nonlinear dynamic model of DNA with a sequence-dependent stacking term
1Theoretical Division and Center for Nonlinear Studies, Los Alamos National Laboratory, Los Alamos, NM 87545 and 2Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA
*To whom correspondence should be addressed. Tel: +1 617 632 0522; Fax: +1 617 632 2927; Email: ausheva{at}bidmc.harvard.edu Correspondence may also be addressed to Kim Ø. Rasmussen. Tel: +1 505 665 3851; Fax: +1 505 665 4063; Email: kor{at}lanl.gov
Received November 18, 2008. Revised January 6, 2009. Accepted January 7, 2009.
No simple model exists that accurately describes the melting behavior and breathing dynamics of double-stranded DNA as a function of nucleotide sequence. This is especially true for homogenous and periodic DNA sequences, which exhibit large deviations in melting temperature from predictions made by additive thermodynamic contributions. Currently, no method exists for analysis of the DNA breathing dynamics of repeats and of highly G/C- or A/T-rich regions, even though such sequences are widespread in vertebrate genomes. Here, we extend the nonlinear Peyrard–Bishop–Dauxois (PBD) model of DNA to include a sequence-dependent stacking term, resulting in a model that can accurately describe the melting behavior of homogenous and periodic sequences. We collect melting data for several DNA oligos, and apply Monte Carlo simulations to establish force constants for the 10 dinucleotide steps (CG, CA, GC, AT, AG, AA, AC, TA, GG, TC). The experiments and numerical simulations confirm that the GG/CC dinucleotide stacking is remarkably unstable, compared with the stacking in GC/CG and CG/GC dinucleotide steps. The extended PBD model will facilitate thermodynamic and dynamic simulations of important genomic regions such as CpG islands and disease-related repeats.
The authors wish it to be known that, in their opinion, the first two authors should be regarded as joint First Authors.