Local modulation of temperature has emerged as a new mechanism for regulation of molecular transport through nanopores. Predicting the effect of such modulations on nanopore transport requires simulation protocols capable of reproducing non-uniform temperature gradients observed in experiment. Conventional molecular dynamics (MD) method typically employs a single thermostat for maintaining a uniform distribution of temperature in the entire simulation domain, and, therefore, can not model local temperature variations. In this article, we describe a set of simulation protocols that enable modeling of nanopore systems featuring non-uniform distributions of temperature. First, we describe a method to impose a temperature gradient in all-atom MD simulations based on a boundary-driven non-equilibrium MD protocol. Then, we use this method to study the effect of temperature gradient on the distribution of ions in bulk solution (the thermophoretic effect). We show that DNA nucleotides exhibit differential response to the same temperature gradient. Next, we describe a method to directly compute the effective force of a thermal gradient on a prototypical biomolecule—a fragment of double-stranded DNA. Following that, we demonstrate an all-atom MD protocol for modeling thermophoretic effects in solid-state nanopores. We show that local heating of a nanopore volume can be used to regulate the nanopore ionic current. Finally, we show how continuum calculations can be coupled to a coarse-grained model of DNA to study the effect of local temperature modulation on electrophoretic motion of DNA through plasmonic nanopores. The computational methods described in this article are expected to find applications in rational design of temperature-responsive nanopore systems.

中文翻译：

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在固态纳米孔中模拟热泳效应。

温度的局部调节已经成为调节通过纳米孔的分子运输的新机制。预测这种调制对纳米孔传输的影响，需要能够重现实验中观察到的非均匀温度梯度的模拟方案。常规分子动力学（MD）方法通常使用单个恒温器来在整个仿真域中保持温度的均匀分布，因此无法对局部温度变化进行建模。在本文中，我们描述了一组模拟协议，这些协议能够对具有非均匀温度分布的纳米孔系统进行建模。首先，我们描述了一种基于边界驱动的非平衡MD协议在全原子MD模拟中施加温度梯度的方法。然后，我们使用这种方法研究温度梯度对本体溶液中离子分布的影响（热泳效应）。我们表明，DNA核苷酸对相同的温度梯度表现出不同的响应。接下来，我们描述一种直接计算热梯度对原型生物分子（双链DNA片段）的有效力的方法。之后，我们演示了用于模拟固态纳米孔中热泳效应的全原子MD方案。我们表明，纳米孔体积的局部加热可用于调节纳米孔离子电流。最后，我们展示了如何将连续谱计算与DNA的粗粒模型耦合，以研究局部温度调节对通过等离子纳米孔的DNA电泳运动的影响。