Interfacial water as a "hydration fingerprint" in the noncognate complex of BamHI.
Interfacial water as a "hydration fingerprint" in the noncognate complex of BamHI.
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DOI：
10.1529/biophysj.105.063263
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发表时间：
2005-08
影响因子：
3.4
通讯作者：
M. Fuxreiter;M. Mezei;I. Simon;R. Osman
中科院分区：
文献类型：
--
作者：
M. Fuxreiter;M. Mezei;I. Simon;R. Osman
蛋白质识别DNA的分子密码在分子生物学中一直是个未解之谜，这主要是因为蛋白质与DNA的直接相互作用与水和离子的间接作用之间存在着微妙的相互作用。随着界面水分子的释放，非特异性、低亲和力的复合体转变为特定的、高亲和力的复合体。为了深入了解从松散到紧密的转变，我们表征了具有非同源序列的BamHI复合体和特定复合体中蛋白质-DNA界面上的水的结构和能量。采用大正则蒙特卡罗模拟方法建立了全水化模型。邻近分析表明，在这两个复合体中，水的分布表现出依赖于序列的变化，特别是在非同源复合体中，它们区分正确的位置和恒星位置。水分布的变化控制着从松散到紧密络合物转变时从给定序列释放的水分子的数量，以及局部熵对结合自由能的贡献。我们认为界面水可以作为给定DNA序列的“水合指纹”。
The molecular code of specific DNA recognition by proteins as a paradigm in molecular biology remains an unsolved puzzle primarily because of the subtle interplay between direct protein-DNA interaction and the indirect contribution from water and ions. Transformation of the nonspecific, low affinity complex to a specific, high affinity complex is accompanied by the release of interfacial water molecules. To provide insight into the conversion from the loose to the tight form, we characterized the structure and energetics of water at the protein-DNA interface of the BamHI complex with a noncognate sequence and in the specific complex. The fully hydrated models were produced with Grand Canonical Monte Carlo simulations. Proximity analysis shows that water distributions exhibit sequence dependent variations in both complexes and, in particular, in the noncognate complex they discriminate between the correct and the star site. Variations in water distributions control the number of water molecules released from a given sequence upon transformation from the loose to the tight complex as well as the local entropy contribution to the binding free energy. We propose that interfacial waters can serve as a "hydration fingerprint" of a given DNA sequence.