How to accelerate protein search on DNA: location and dissociation

One of the most important features of biological systems that controls their functioning is the ability of protein molecules to find and recognize quickly specific target sites on DNA. Although these phenomena have been studied extensively, detailed mechanisms of protein-DNA interactions during the search are still not well understood. Experiments suggest that proteins typically find their targets fast by combining three-dimensional and one-dimensional motions, and most of the searching time proteins are non-specifically bound to DNA. However these observations are surprising since proteins diffuse very slowly on DNA, and it seems that the observed fast search cannot be achieved under these conditions for single proteins. Here we propose two simple mechanisms that might explain some of these controversial observations. Using first-passage time analysis, it is shown explicitly that the search can be accelerated by changing the location of the target and by effectively irreversible dissociations of proteins. Our theoretical predictions are supported by Monte Carlo computer simulations.