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

Sequence Heterogeneity Accelerates Protein Search for Targets on DNA