De novo reconstruction of DNA origami structures through atomistic molecular dynamics simulation.
De novo reconstruction of DNA origami structures through atomistic molecular dynamics simulation.
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DOI：
10.1093/nar/gkw155
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发表时间：
2016-04-20
影响因子：
14.9
通讯作者：
Aksimentiev A
中科院分区：
文献类型：
--
作者：
Maffeo C;Yoo J;Aksimentiev A
DNA折纸方法为分子生物学实验室带来了纳米级精度的制造，在合成生物学、医学、分子计算等领域提供了无数潜在的应用。进一步推进该方法需要将自组装控制到原子尺度。在这里，我们演示了一种计算方法，可以将大型复杂 DNA 折纸物体的平衡结构确定为原子分辨率。通过与冷冻电子显微镜结果的直接比较，我们通过完全原子分子动力学模拟展示了 4.7 兆道尔顿指针结构的从头重建。此外，我们表明，在没有溶剂的情况下进行的弹性网络引导模拟可以以一小部分计算成本产生类似的精度，使得该方法成为自组装 DNA 纳米结构的原型设计和验证的有吸引力的方法。
The DNA origami method has brought nanometer-precision fabrication to molecular biology labs, offering myriads of potential applications in the fields of synthetic biology, medicine, molecular computation, etc. Advancing the method further requires controlling self-assembly down to the atomic scale. Here we demonstrate a computational method that allows the equilibrium structure of a large, complex DNA origami object to be determined to atomic resolution. Through direct comparison with the results of cryo-electron microscopy, we demonstrate de novo reconstruction of a 4.7 megadalton pointer structure by means of fully atomistic molecular dynamics simulations. Furthermore, we show that elastic network-guided simulations performed without solvent can yield similar accuracy at a fraction of the computational cost, making this method an attractive approach for prototyping and validation of self-assembled DNA nanostructures.