Published online 27 August 2004
Nucleic Acids Research, Vol. 32 No. 15 © Oxford University Press 2004; all rights reserved
Rational design of DNA sequences for nanotechnology, microarrays and molecular computers using Eulerian graphs
Department of Pathology, Stony Brook University, New York, NY 11794, USA and 1 Charles University, Faculty of Mathematics and Physics, 12116 Prague 2, Czech Republic
* To whom correspondence should be addressed. Tel: +1 631 444 3030; Fax: +1 631 444 2459; Email: ppancoska{at}notes.cc.sunysb.edu
Correspondence may also be addressed to Zdenek Moravek. Tel: +49 941 944 7602; Fax: +420 22191 1249; Email: moravek{at}alma.karlov.mff.cuni.cz
Received April 21, 2004; Revised May 25, 2004; Accepted August 16, 2004
Nucleic acids are molecules of choice for both established and emerging nanoscale technologies. These technologies benefit from large functional densities of ‘DNA processing elements’ that can be readily manufactured. To achieve the desired functionality, polynucleotide sequences are currently designed by a process that involves tedious and laborious filtering of potential candidates against a series of requirements and parameters. Here, we present a complete novel methodology for the rapid rational design of large sets of DNA sequences. This method allows for the direct implementation of very complex and detailed requirements for the generated sequences, thus avoiding ‘brute force’ filtering. At the same time, these sequences have narrow distributions of melting temperatures. The molecular part of the design process can be done without computer assistance, using an efficient ‘human engineering’ approach by drawing a single blueprint graph that represents all generated sequences. Moreover, the method eliminates the necessity for extensive thermodynamic calculations. Melting temperature can be calculated only once (or not at all). In addition, the isostability of the sequences is independent of the selection of a particular set of thermodynamic parameters. Applications are presented for DNA sequence designs for microarrays, universal microarray zip sequences and electron transfer experiments.
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