The Singapore-MIT Alliance, National University of Singapore, Singapore.
Phys Chem Chem Phys. 2012 Sep 21;14(35):12277-84. doi: 10.1039/c2cp41638g. Epub 2012 Aug 8.
Water plays an important role in protein-DNA interactions. Here, we examine using molecular dynamics simulations the differences in the dynamic and thermodynamic properties of water in the interfacial and intercalating regions of EcoRI bound to the cognate and to a minimally mutated noncognate DNA chain. The results show that the noncognate complex is not only more hydrated than the cognate complex, but the interfacial waters in the noncognate complex exhibit a faster dynamics, which in turn reduces the hydrogen-bond lifetimes. Thus, the higher hydration, faster reorientation dynamics and faster hydrogen-bond-relaxation times of water, taken together, indicate that, even with a minimal mutation of the DNA sequence, the interfacial regions of the noncognate complex are more poised to allowing the protein to diffuse away than to promoting the formation of a stable complex. Alternatively, the results imply that the slowed water dynamics in the interfacial regions when the protein chances upon a cognate sequence allow the formation of a stable specific protein-DNA complex leading to catalytic action.
水在蛋白质-DNA 相互作用中起着重要作用。在这里，我们使用分子动力学模拟研究了 EcoRI 与同源和最小突变非同源 DNA 链结合时，界面和嵌入区域中水分子的动态和热力学性质的差异。结果表明，非同源复合物不仅比同源复合物更具水合性，而且非同源复合物中的界面水具有更快的动力学，这反过来又缩短了氢键的寿命。因此，水的更高水合度、更快的重新取向动力学和更快的氢键松弛时间表明，即使 DNA 序列发生微小突变，非同源复合物的界面区域也更有利于允许蛋白质扩散，而不是促进稳定复合物的形成。或者，这些结果表明，当蛋白质遇到同源序列时，界面区域水动力学的减缓允许形成稳定的特定蛋白质-DNA 复合物，从而导致催化作用。
