Computation of DNA structural variability—a new predictor of DNA regulatory regions

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Abstract
Local separation of the two strands of the DNA duplex is an essential step in important biological activities, including the initiation of transcription and replication. This conformational transition occurs in response to imposed stresses, which are stringently regulated in vivo. This paper describes two computational methods to analyse this phenomenon: an approximate statistical mechanical method and a Monte Carlo sampling technique. Analysis of genomic DNA sequences shows that sites of predicted duplex destabilization are closely associated with regions regulating transcription, with the most destabilized sites coinciding with 3′ gene termini. Experimental results supporting this conclusion are described. The incorporation of this technique into computational searches for regulatory regions is discussed. Because the programs implementing these calculations are complex to use and not completely developed, they have not been released yet. However, the author will analyze any DNA sequences upon request. Sequences may be submitted electronically to benham@msvax.mssm.edu.

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