Target search on a dynamic DNA molecule

TL;DR

This study models protein target search on a dynamic DNA molecule, revealing that DNA motion significantly enhances search efficiency by facilitating jumps and reducing redundant exploration, especially compared to static DNA.

Contribution

It introduces a dynamic DNA model for protein search, highlighting the importance of DNA motion in optimizing search strategies and characterizing the transition between static and dynamic DNA regimes.

Findings

DNA dynamics improve protein jump efficiency

Fast DNA motion reduces redundant search

Slow DNA leads to trapping in DNA islands

Abstract

We study a protein-DNA target search model with explicit DNA dynamics applicable to in vitro experiments. We show that the DNA dynamics plays a crucial role for the effectiveness of protein "jumps" between sites distant along the DNA contour but close in 3D space. A strongly binding protein that searches by 1D sliding and jumping alone, explores the search space less redundantly when the DNA dynamics is fast on the timescale of protein jumps than in the opposite "frozen DNA" limit. We characterize the crossover between these limits using simulations and scaling theory. We also rationalize the slow exploration in the frozen limit as a subtle interplay between long jumps and long trapping times of the protein in "islands" within random DNA configurations in solution.