In this work, we employ simple model systems to evaluate the relative performance of two of the most important free energy methods: The Zwanzig equation (also known as ‘Free energy perturbation’) and Bennett’s acceptance ratio method (BAR). Although our examples should be transferable to other kinds of free energy simulations, we focus on applications of multi-scale free energy simulations. Such calculations are especially complex, since they connect two different levels of theory with very different requirements in terms of speed, accuracy, sampling and parallelisability. We try to reconcile all those different factors by developing some simple criteria to guide the early stages of the development of a free energy protocol. This is accomplished by quantifying how many intermediate steps and how many potential energy evaluations are necessary in order to reach a certain level of convergence.

中文翻译：

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关于多尺度自由能模拟的收敛性

在这项工作中，我们使用简单的模型系统来评估两种最重要的自由能方法的相对性能：Zwanzig 方程（也称为“自由能扰动”）和 Bennett 接受率方法 (BAR)。虽然我们的例子应该可以转移到其他类型的自由能模拟，但我们专注于多尺度自由能模拟的应用。这种计算特别复杂，因为它们将两个不同层次的理论联系起来，在速度、准确性、采样和并行性方面的要求截然不同。我们试图通过制定一些简单的标准来指导自由能协议发展的早期阶段来协调所有这些不同的因素。