  Recent experiments show that transcription factors (TFs) indeed use the
facilitated diffusion mechanism to locate their target sequences on DNA in
living bacteria cells: TFs alternate between sliding motion along DNA and
relocation events through the cytoplasm. From simulations and theoretical
analysis we study the TF-sliding motion for a large section of the DNA-sequence
of a common E. coli strain, based on the two-state TF-model with a fast-sliding
search state and a recognition state enabling target detection. For the
probability to detect the target before dissociating from DNA the TF-search
times self-consistently depend heavily on whether or not an auxiliary operator
(an accessible sequence similar to the main operator) is present in the genome
section. Importantly, within our model the extent to which the interconversion
rates between search and recognition states depend on the underlying nucleotide
sequence is varied. A moderate dependence maximises the capability to
distinguish between the main operator and similar sequences. Moreover, these
auxiliary operators serve as starting points for DNA looping with the main
operator, yielding a spectrum of target detection times spanning several orders
of magnitude. Auxiliary operators are shown to act as funnels facilitating
target detection by TFs.
