Protein Search for Multiple Targets on DNA

Abstract

Fast and precise protein binding to the specific sites on DNA is essential for majority of biological processes. A large number of experimental and theoretical investigations have been devoted to explaining the molecular mechanisms of protein search and recognition of the targets, but the details are still not well understood. For eukaryotic genomes one of the most interesting problems is the role of multiple targets in the protein search dynamics. Using earlier developed theoretical framework based on a discrete-state stochastic approach, we derived full analytical description of all dynamic properties of protein-DNA system. It was found that multiple targets in most cases accelerate the search in comparison with a single target situation. Nevertheless, the acceleration is not always proportional to the number of targets and depends on critical parameters: spatial position of the targets, distances between them, average scanning lengths of protein molecules on DNA, and the total DNA lengths. Moreover, there are even situations when to find the properly positioned single target is faster than one of the multiple targets! Our results were compared with experimental observations as well as with results from a continuum theory for the protein search. Also, extensive Monte Carlo computer simulations and physical-chemical arguments fully support our theoretical calculations.