DNA library design for molecular computation.
A novel approach to designing a DNA library for molecular computation is presented. The method is employed for encoding binary information in DNA molecules. It aims to achieve a practical discrimination between perfectly matched DNA oligomers and those with mismatches in a large pool of different molecules. The approach takes into account the ability of DNA strands to hybridize in complex structures like hairpins, internal loops, or bulge loops and computes the stability of the hybrids formed based on thermodynamic data. A dynamic programming algorithm is applied to calculate the partition function for the ensemble of structures, which play a role in the hybridization reaction. The applicability of the method is demonstrated by the design of a twelve-bit DNA library. The library is constructed and experimentally tested using molecular biology tools. The results show a high level of specific hybridization achieved for all library words under identical conditions. The method is also applicable for the design of primers for PCR, DNA sequences for isothermal amplification reactions, and capture probes in DNA-chip arrays. The library could be applied for integrated DNA computing of twelve-bit instances of NP-complete combinatorial problems by multi-step DNA selection in microflow reactors.
Penchovsky
Robert
R
Biomolecular Information Processing (BioMIP), Fraunhofer Gesellschaft, Schloss Birlinghoven, D-53754 Sankt Augustin, Germany. Robert_Penchovsky@web.de
Ackermann
Jörg
J
D000465:Algorithms; D001483:Base Sequence; D019295:Computational Biology; D004247:DNA / Q000737:chemistry*; D015723:Gene Library; D005821:Genetic Techniques; D008969:Molecular Sequence Data; D009693:Nucleic Acid Hybridization; D009838:Oligodeoxyribonucleotides
D009838:Oligodeoxyribonucleotides; D004247:DNA