DNA sequence-dependent deformability associated with hydration; Implication for indirect readout in protein-DNA interactions

Kono, Hidetoshi; Yonetani, Yoshiteru*; Fujii, Satoshi*; Sarai, Akinori*; Go, Nobuhiro

Proteins recognize specific DNA sequences not only through direct contact between amino acids and base-pairs, but also indirectly based on the sequence-dependent conformation and deformability of the DNA (indirect readout). We used molecular dynamics simulations to analyze the sequence-dependent DNA conformations of all 136 possible tetramericsequences sandwiched between CGCG sequences. We found that the average conformation and deformability of the tetramers can be highly sequence dependent. Even the tetrameric sequences having the same dimeric sequence at the center showed the distinct deformabilities dependent on the bases on either end of the tetramers. Such conformations of tetramers were found to be associated with hydration. The tetrameric sequences with AT at their center, for instance, generally were rigid and highly hydrated. The rigidity among the tetramers was affected by the flanking bases and also correlated with the amount of hydration which we defined as number of water molecules bridging two bases belonging to different chains in minor groove. These results suggest that hydration of DNA is responsible for the mechanism of indirect readout during protein-DNA recognition. We also show that the sequence dependence of DNA conformation and deformability may be used to estimate the contribution of indirect readout to the specificity of protein-DNA recognition as well as nucleosome positioning and large-scale behavior of nucleic acids.