  In bacteria, regulatory proteins search for a specific DNA binding target via
"facilitated diffusion": a series of rounds of 3D diffusion in the cytoplasm,
and 1D linear diffusion along the DNA contour. Using large scale Brownian
dynamics simulations we find that each of these steps is affected differently
by crowding proteins, which can either be bound to the DNA acting as a road
block to the 1D diffusion, or freely diffusing in the cytoplasm. Macromolecular
crowding can strongly affect mechanistic features such as the balance between
3D and 1D diffusion, but leads to surprising robustness of the total search
time.
