Energetic funnel facilitates facilitated diffusion


Transcription factors are proteins able to bind specific sites of DNA such as to promote or inhibit DNA transcription. Such proteins are able to associate to their target sites 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 and proposed in the ’80s by Berg and von Hippel. In this talk I will show that the binding energy landscape around the target sequences of Escherichia coli and of Bacillus subtilis is organized in a funnel-like structure. Such funnel traces back to gradients of AT in the base composition in the DNA region around the binding sites. By means of an extensive computational study of the stochastic sliding process along the energetic landscapes obtained from the database I will show that the funnel can significantly enhance the probability of transcription factors to find their target sequences when sliding in their proximity. Such enhancement leads to a speed-up of the association process.