Sequence-dependent DNA deformability studied using molecular dynamics simulations

分子動力学計算によるDNAの配列に依存した構造変形能解析

藤井 聡*; 河野 秀俊; 竹中 繁織*; 郷 信広; 皿井 明倫*

Fujii, Satoshi*; Kono, Hidetoshi; Takenaka, Shigeori*; Go, Nobuhiro; Sarai, Akinori*

タンパク質がDNAを認識するには、DNAとの水素結合や静電相互作用による直接的な認識とDNAの構造特性に由来した間接的な認識がある。われわれは、後者の間接的な認識を定量化するために、DNAの構造特性を分子動力学計算によって調べた。結果、これまで2塩基対で特徴づけられていた構造は、その特性を記述するのに不十分であること、塩基対の配列依存性が2つ先の塩基対までかなり影響することなどを示した。さらに、間接認識ポテンシャルを作成し、それが細胞内で見られるDNAのヌクレオソーム構造形領域を予測できることを示した。

Proteins recognize specific DNA sequences not only through direct contact between amino acids and bases, 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 tetrameric sequences sandwiched between CGCG sequences. The deformability of dimeric steps obtained by the simulations is consistent with that by the crystal structures. The simulation results further showed that the conformation and deformability of the tetramers can highly depend on the flanking base-pairs. The conformations of xATx tetramers show the most rigidity and are not affected by the flanking base-pairs and the xYRx show by contrast the greatest flexibility and change their conformations depending on the base-pairs at both ends, suggesting tetramers with the same central dimer can show different deformabilities. These results suggest that analysis of dimeric steps alone may overlook some conformational features of DNA and provide insight into the mechanism of indirect readout during protein-DNA recognition. Moreover, 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.