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Nucleic Acids Research 2005 33(15):4965-4977; doi:10.1093/nar/gki812
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Published online 2 September 2005

© The Author 2005. Published by Oxford University Press. All rights reserved
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Article

A thermodynamic approach to designing structure-free combinatorial DNA word sets

Michael R. Shortreed, Seo Bong Chang, DongGee Hong, Maggie Phillips, Bridget Campion, Dan C. Tulpan1, Mirela Andronescu1, Anne Condon1, Holger H. Hoos1 and Lloyd M. Smith*

Department of Chemistry, University of Wisconsin Madison, WI 53706-1396, USA 1Department of Computer Science, University of British Columbia Vancouver, BC, Canada V6T 1Z4

*To whom correspondence should be addressed. Tel: +1 608 262 9207; Fax: +1 608 265 6780; Email: smith{at}chem.wisc.edu

Received December 21, 2004. Revised July 1, 2005. Accepted August 17, 2005.

An algorithm is presented for the generation of sets of non-interacting DNA sequences, employing existing thermodynamic models for the prediction of duplex stabilities and secondary structures. A DNA ‘word’ structure is employed in which individual DNA ‘words’ of a given length (e.g. 12mer and 16mer) may be concatenated into longer sequences (e.g. four tandem words and six tandem words). This approach, where multiple word variants are used at each tandem word position, allows very large sets of non-interacting DNA strands to be assembled from combinations of the individual words. Word sets were generated and their figures of merit are compared to sets as described previously in the literature (e.g. 4, 8, 12, 15 and 16mer). The predicted hybridization behavior was experimentally verified on selected members of the sets using standard UV hyperchromism measurements of duplex melting temperatures (Tms). Additional experimental validation was obtained by using the sequences in formulating and solving a small example of a DNA computing problem.


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D. Tulpan, M. Andronescu, S. B. Chang, M. R. Shortreed, A. Condon, H. H. Hoos, and L. M. Smith
Thermodynamically based DNA strand design
Nucleic Acids Res., September 6, 2005; 33(15): 4951 - 4964.
[Abstract] [Full Text] [PDF]


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