Sequence heterogeneity accelerates protein search for targets on DNA

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 sear...

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Bibliographic Details
Published in:The Journal of chemical physics 2015-12, Vol.143 (24), p.245101-245101
Main Authors: Shvets, Alexey A, Kolomeisky, Anatoly B
Format: Article
Language:English
Subjects:
Base Sequence
Binding Sites
Biological activity
Biological effects
CHEMICAL BONDS
CHEMICAL COMPOSITION
Chemical reactions
Deoxyribonucleic acid
Diffusion
DNA
DNA - chemistry
DNA SEQUENCING
Gene sequencing
Heterogeneity
INORGANIC, ORGANIC, PHYSICAL AND ANALYTICAL CHEMISTRY
Monte Carlo Method
Organic chemistry
PROBES
PROTEINS
Proteins - chemistry
Searching
STOCHASTIC PROCESSES
SYMMETRY
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Summary: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.
ISSN:0021-9606
1089-7690
DOI:10.1063/1.4937938