  Transcription factors are able to associate to their binding sites on DNA
faster than the physical limit posed by diffusion. Such high association rates
can be achieved by alternating between three-dimensional diffusion and
one-dimensional sliding along the DNA chain, a mechanism dubbed Facilitated
Diffusion. By studying a collection of transcription factor binding sites of
Escherichia coli from the RegulonDB database and of Bacillus subtilis from
DBTBS, we reveal a funnel in the binding energy landscape around the target
sequences. We show that such a funnel is linked to the presence of gradients of
AT in the base composition in the DNA region around the binding sites. An
extensive computational study of the stochastic sliding process along the
energetic landscapes obtained from the database shows that the funnel can
significantly enhance the probability of transcription factors to find their
target sequences when sliding in their proximity. We demonstrate that this
enhancement leads to a speed-up of the association process.
