Facilitated diffusion in the presence of obstacles on the DNA

Abstract

Biological functions of DNA depend on the sequence-specific binding of DNA-binding proteins to their corresponding binding sites. Binding of these proteins to their binding sites occurs through a facilitated diffusion process that combines three-dimensional diffusion in the cytoplasm with one-dimensional diffusion (sliding) along the DNA. In this work, we use a lattice model of facilitated diffusion to study how the dynamics of binding of a protein to a specific site (e.g., binding of an RNA polymerase to a promoter or of a transcription factor to its operator site) is affected by the presence of other proteins bound to the DNA, which act as 'obstacles' in the sliding process. Different types of these obstacles with different dynamics are implemented. While all types impair facilitated diffusion, the extent of the hindrance depends on the type of obstacle. As a consequence of hindrance by obstacles, more excursions into the cytoplasm are required for optimal target binding compared to the case without obstacles.