De Biase Pablo M, Markosyan Suren, Noskov Sergei
J Comput Chem. 2014 Apr 5;35(9):711-21. doi: 10.1002/jcc.23544.
We developed a novel scheme based on the grand-canonical Monte Carlo/Brownian dynamics simulations and have extended it to studies of ion currents across three nanopores with the potential for single-stranded DNA (ssDNA) sequencing: solid-state nanopore Si₃N₄, α-hemolysin, and E111N/M113Y/K147N mutant. To describe nucleotide-specific ion dynamics compatible with ssDNA coarse-grained model, we used the inverse Monte Carlo protocol, which maps the relevant ion-nucleotide distribution functions from all-atom molecular dynamics (MD) simulations. Combined with the previously developed simulation platform for Brownian dynamics simulations of ion transport, it allows for microsecond- and millisecond-long simulations of ssDNA dynamics in the nanopore with a conductance computation accuracy that equals or exceeds that of all-atom MD simulations. In spite of the simplifications, the protocol produces results that agree with the results of previous studies on ion conductance across open channels and provide direct correlations with experimentally measured blockade currents and ion conductances that have been estimated from all-atom MD simulations.
我们基于巨正则蒙特卡罗/布朗动力学模拟开发了一种新方案，并将其扩展到对具有单链DNA（ssDNA）测序潜力的三个纳米孔中的离子电流的研究：固态纳米孔Si₃N₄、α-溶血素和E111N/M113Y/K147N突变体。为了描述与ssDNA粗粒化模型兼容的核苷酸特异性离子动力学，我们使用了逆蒙特卡罗协议，该协议从全原子分子动力学（MD）模拟中映射相关的离子-核苷酸分布函数。结合先前开发的用于离子输运布朗动力学模拟的模拟平台，它允许对纳米孔中的ssDNA动力学进行微秒级和毫秒级的模拟，其电导计算精度等于或超过全原子MD模拟。尽管有简化，但该协议产生的结果与先前关于开放通道离子电导的研究结果一致，并与从全原子MD模拟估计的实验测量的阻断电流和离子电导提供直接相关性。
