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The functional annotation of the non-protein coding DNA of eukaryotic genomes is a problem of central importance in computational and experimental biology. Several computational approaches for the prediction of regulatory elements were developed during the last decade. Searches for clusters of DNA binding sites for transcription factors in genomic sequences together with phylogenetic footprinting methods, which attempt to identify functional regulatory regions by comparing orthologous genomic sequences of evolutionarily related species, have shown promising results.

Now we attempt to refine prediction of binding sites for transcription factors with employing structural information on protein/DNA binding. We have shown that small sequence-dependent deformations of DNA structure and changing electrostatic properties of DNA can encode for specific recognition by individual members of families of transcription factors. Combination of DNA structure prediction with understanding of structural features required for specific protein/DNA recognition can improve our ability to recognize specific binding sites in genomic sequences.