The Binding Process of a Nonspecific Enzyme with DNA
The Binding Process of a Nonspecific Enzyme with DNA
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DOI：
10.1016/j.bpj.2011.07.016
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发表时间：
2011-09-07
影响因子：
3.4
通讯作者：
Pettitt, B. Montgomery
中科院分区：
文献类型：
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作者：
Chen, Chuanying;Pettitt, B. Montgomery
对非特异性复合物的蛋白质-DNA 识别进行建模，以了解瞬时遭遇状态的本质。我们考虑了 DNA 凹槽中水的结构和能量特征以及蛋白质-DNA 识别过程中的作用。在这里，我们使用来自大肠杆菌的大肠菌素 E7 (N-ColE7) 的核酸酶结构域与 12 bp DNA 双链体复合物作为模型系统来考虑蛋白质如何接近、遇到和关联 DNA。使用布朗动力学和分子动力学模拟进行多尺度模拟研究，以提供多个长度和时间尺度上的结合过程。我们定义遭遇状态并确定空间和方向方面。对于分子长度尺度，我们使用分子动力学模拟。发现了几种中间结合状态，它们在 DNA 周围具有不同的蛋白质位置和方向，包括大沟和小沟方向。结果表明，接触数和水合界面面积有助于更好地理解序列无关的蛋白质-DNA 结合景观和途径。
Protein-DNA recognition of a nonspecific complex is modeled to understand the nature of the transient encounter states. We consider the structural and energetic features and the role of water in the DNA grooves in the process of protein-DNA recognition. Here we have used the nuclease domain of colicin E7 (N-ColE7) from Escherichia coli in complex with a 12-bp DNA duplex as the model system to consider how a protein approaches, encounters, and associates with DNA. Multiscale simulation studies using Brownian dynamics and molecular-dynamics simulations were performed to provide the binding process on multiple length- and timescales. We define the encounter states and identified the spatial and orientational aspects. For the molecular length-scales, we used molecular-dynamics simulations. Several intermediate binding states were found, which have different positions and orientations of protein around DNA including major and minor groove orientations. The results show that the contact number and the hydrated interfacial area are measures that facilitate better understanding of sequence-independent protein-DNA binding landscapes and pathways.