Sliding Dynamics Along DNA: A Molecular Perspective

Abstract

Rapid recognition of DNA target sites involves facilitated diffusion through which alternative sites are searched on genomic DNA. One of the key mechanisms in the localization of the target by a DNA binding protein is one-dimensional diffusion (sliding) in which the protein is attracted to the DNA by electrostatic forces. During the search, the protein faces both a thermodynamic and a kinetic challenge, as it needs to rapidly recognize and tightly bind a specific DNA sequence within an enormous background of nonspecific genomic sites and competing macromolecular species. Understanding the nature of interactions between regulatory proteins and nonspecific DNA sequences is required in order to decipher the structural and dynamic features that underlie protein–DNA recognition processes. In this review, we discuss a simplified computational approach that represents protein–DNA interactions by electrostatic forces. We provide structural criteria that distinguish between different search mechanisms and show that the protein makes use of similar binding interfaces for both nonspecific and specific interactions. The presented model captures various experimental features of facilitated diffusion and has the potency to address other questions regarding the nature of DNA search, such as the sliding characteristics of oligomeric and multidomain DNA binding proteins that are ubiquitous in the cell.