Cuervo Ana, Dans Pablo D, Carrascosa José L, Orozco Modesto, Gomila Gabriel, Fumagalli Laura
Department of Structure of Macromolecules, Centro Nacional de Biotecnologia-Consejo Superior de Investigaciones Cientificas, Campus Cantoblanco, 28049 Madrid, Spain;
Institute for Research in Biomedicine-Barcelona Supercomputing Center Joint Research Program in Computational Biology, Institute for Research in Biomedicine-Barcelona, 08028 Barcelona, Spain;
Proc Natl Acad Sci U S A. 2014 Sep 2;111(35):E3624-30. doi: 10.1073/pnas.1405702111. Epub 2014 Aug 18.
The electric polarizability of DNA, represented by the dielectric constant, is a key intrinsic property that modulates DNA interaction with effector proteins. Surprisingly, it has so far remained unknown owing to the lack of experimental tools able to access it. Here, we experimentally resolved it by detecting the ultraweak polarization forces of DNA inside single T7 bacteriophages particles using electrostatic force microscopy. In contrast to the common assumption of low-polarizable behavior like proteins (εr ∼ 2-4), we found that the DNA dielectric constant is ∼ 8, considerably higher than the value of ∼ 3 found for capsid proteins. State-of-the-art molecular dynamic simulations confirm the experimental findings, which result in sensibly decreased DNA interaction free energy than normally predicted by Poisson-Boltzmann methods. Our findings reveal a property at the basis of DNA structure and functions that is needed for realistic theoretical descriptions, and illustrate the synergetic power of scanning probe microscopy and theoretical computation techniques.
由介电常数表示的DNA电极化率是调节DNA与效应蛋白相互作用的关键内在特性。令人惊讶的是,由于缺乏能够测量它的实验工具,到目前为止它仍然未知。在这里,我们通过使用静电力显微镜检测单个T7噬菌体颗粒内DNA的超弱极化力,通过实验解决了这个问题。与蛋白质(εr ∼ 2-4)的低极化行为这一常见假设相反,我们发现DNA介电常数约为8,大大高于衣壳蛋白的约3的值。最先进的分子动力学模拟证实了实验结果,这导致DNA相互作用自由能比泊松-玻尔兹曼方法通常预测的明显降低。我们的发现揭示了DNA结构和功能基础上的一种特性,这是现实理论描述所必需的,并说明了扫描探针显微镜和理论计算技术的协同作用。