Energetic funnel facilitates facilitated diffusion

Transcription factors (TFs) 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 TF bind- ing 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 of 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 TFs to find their target sequences when sliding in their proximity. We demonstrate that this enhance- ment leads to a speed-up of the association process.