Sequence heterogeneity accelerates protein search for targets on DNA

J Chem Phys. 2015 Dec 28;143(24):245101. doi: 10.1063/1.4937938.

Abstract

The process of protein search for specific binding sites on DNA is fundamentally important since it marks the beginning of all major biological processes. We present a theoretical investigation that probes the role of DNA sequence symmetry, heterogeneity, and chemical composition in the protein search dynamics. Using a discrete-state stochastic approach with a first-passage events analysis, which takes into account the most relevant physical-chemical processes, a full analytical description of the search dynamics is obtained. It is found that, contrary to existing views, the protein search is generally faster on DNA with more heterogeneous sequences. In addition, the search dynamics might be affected by the chemical composition near the target site. The physical origins of these phenomena are discussed. Our results suggest that biological processes might be effectively regulated by modifying chemical composition, symmetry, and heterogeneity of a genome.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Base Sequence
  • Binding Sites
  • DNA / chemistry*
  • Diffusion
  • Monte Carlo Method
  • Proteins / chemistry*
  • Stochastic Processes

Substances

  • Proteins
  • DNA