A Software Tool for Generating Non-crosshybridizing Libraries of DNA Oligonucleotides

  • Authors:

  • Russell Deaton;Junghuei Chen;Hong Bi;John A. Rose

  • Affiliations:

  • -;-;-;-

  • Venue:
  • DNA8 Revised Papers from the 8th International Workshop on DNA Based Computers: DNA Computing
  • Year:
  • 2002

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Abstract

Under an all or nothing hybridization model, the problem of finding a library of non-crosshybridizing DNA oligonucleotides is shown to be equivalent to finding an independent set of vertices in a graph. Individual oligonucleotides or Watson-Crick pairs are represented as vertices. Indicating a hybridization, an edge is placed between vertices (oligonu-cleotides or pairs) if the minimum free energy of hybridization, according to the nearest-neighbor model of duplex thermal stability, is less than some threshold value. Using this equivalence, an algorithm is implemented to find maximal libraries. Sequence designs were generated for a test of a modified PCR protocol. The results indicated that the designed structures formed as planned, and that there was little to no secondary structure present in the single-strands. In addition, simulations to find libraries of 10-mers and 20-mers were done, and the base composition of the non-crosshybridizing libraries was found to be 2/3 A-T and 1/3 G-C under high salt conditions, and closer to uniform for lower salt concentrations.