How does a protein search for the specific site on DNA: the role of disorder

TL;DR

This paper investigates how protein disorder influences the efficiency of DNA target search, revealing that energy landscape heterogeneity can slow down the search process, with effects varying between macroscopic and mesoscopic scales.

Contribution

It introduces the impact of energy dispersion within the DNA-protein interaction landscape on the search efficiency, highlighting differences between macroscopic and mesoscopic antennas.

Findings

Random energy profiles slow down the search rate.

The slowdown effect differs between macroscopic and mesoscopic antennas.

Abstract

Proteins can locate their specific targets on DNA up to two orders of magnitude faster than the Smoluchowski three-dimensional diffusion rate. This happens due to non-specific adsorption of proteins to DNA and subsequent one-dimensional sliding along DNA. We call such one-dimensional route towards the target "antenna". We studied the role of the dispersion of nonspecific binding energies within the antenna due to quasi random sequence of natural DNA. Random energy profile for sliding proteins slows the searching rate for the target. We show that this slowdown is different for the macroscopic and mesoscopic antennas.