How proteins find and recognize targets on DNA

Protein searching and recognizing the targets on DNA is an important initial step in many biological processes. It is often argued that some proteins are capable of finding their targets 10-100 times faster than predicted by the three-dimensional diffusion rate. Current theoretical view of this phenomenon is based on the idea of lowering dimensionality, i.e., the overall search process is viewed as a combination of uncorrelated 3D excursions in the solution and 1D hopping on DNA. However, some predictions of this theoretical picture contradict recent single-molecule measurements of protein diffusion along the DNA molecule. We present an alternative theoretical approach that points out into importance of correlations during the search process. That correlations appear due to non-specific interactions between proteins and DNA molecules. Our theoretical predictions agree with all available experimental observations, as well as with extensive lattice Monte Carlo simulations. It is argued that the acceleration in the search could only be achieved at some intermediate non-specific binding energies and proteins concentrations.