Infinite switch simulated tempering in force (FISST)
Infinite switch simulated tempering in force (FISST)
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DOI：
10.1063/5.0009280
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发表时间：
2020-06-28
影响因子：
4.4
通讯作者：
Hocky, Glen M.
中科院分区：
文献类型：
--
作者：
Hartmann, Michael J.;Singh, Yuvraj;Hocky, Glen M.
细胞中的许多蛋白质能够感知并响应皮牛顿级的力，在这种情况下，构象变化很小，但对生物过程意义重大。为了高效且有效地对这些蛋白质对小力的响应进行采样，需要增强的采样技术。在这项工作中，我们推导、实施和评估一种有效的方法，以同时对在指定范围内向感兴趣的分子系统施加任何恒定拉力的结果进行采样。我们从力的模拟回火开始，力作为集体变量的线性偏差添加到系统的哈密顿量中，并且系数被视为连续的辅助自由度。我们推导出一个平均集体变量相关力的公式，该公式取决于在整个模拟过程中动态学习的一组权重，反映了力无限快速变化的极限。然后，模拟数据可用于追溯计算指定范围内任何力下任何可观测值的平均值。该技术基于最近推导出无限开关模拟温度回火的类似方程的工作，该方程表明无限开关极限对于采样来说是最有效的。在这里，我们证明了我们的方法可以同时在用户定义的力范围内的所有力下准确地对分子系统进行采样，并展示了它如何作为增强的采样工具，用于处理拉力方向使零力下具有低自由能的状态不稳定的情况。该方法在 PLUMED 开源采样库中实现并免费分发，因此可以轻松应用于使用各种分子动力学软件包的问题。
Many proteins in cells are capable of sensing and responding to piconewton-scale forces, a regime in which conformational changes are small but significant for biological processes. In order to efficiently and effectively sample the response of these proteins to small forces, enhanced sampling techniques will be required. In this work, we derive, implement, and evaluate an efficient method to simultaneously sample the result of applying any constant pulling force within a specified range to a molecular system of interest. We start from simulated tempering in force, whereby force is added as a linear bias on a collective variable to the system's Hamiltonian, and the coefficient is taken as a continuous auxiliary degree of freedom. We derive a formula for an average collective-variable-dependent force, which depends on a set of weights learned on-the-fly throughout a simulation, that reflect the limit where force varies infinitely quickly. Simulation data can then be used to retroactively compute averages of any observable at any force within the specified range. This technique is based on recent work deriving similar equations for infinite switch simulated tempering in temperature, which showed that the infinite switch limit is the most efficient for sampling. Here, we demonstrate that our method accurately samples molecular systems at all forces within a user defined force range simultaneously and show how it can serve as an enhanced sampling tool for cases where the pulling direction destabilizes states that have low free-energy at zero-force. This method is implemented in and freely distributed with the PLUMED open-source sampling library, and hence can be readily applied to problems using a wide range of molecular dynamics software packages.