Reinhardt Martin, Grubmüller Helmut
Max Planck Institute for Biophysical Chemistry, 37077 Göttingen, Germany.
Phys Rev E. 2020 Oct;102(4-1):043312. doi: 10.1103/PhysRevE.102.043312.
Free-energy difference calculations based on atomistic simulations generally improve in accuracy when sampling from a sequence of intermediate equilibrium thermodynamic states that bridge the configuration space between two states of interest. For reasons of efficiency, usually the same samples are used to calculate the stepwise difference of such an intermediate to both adjacent intermediates. However, this procedure violates the assumption of uncorrelated estimates that is necessary to derive both the optimal sequence of intermediate states and the widely used Bennett acceptance ratio estimator. In this work, via a variational approach, we derive the sequence of intermediate states and the corresponding estimator with minimal mean-squared error that account for these correlations and assess its accuracy.
基于原子模拟的自由能差计算，当从一系列中间平衡热力学状态进行采样时，通常会提高准确性，这些中间状态跨越了两个感兴趣状态之间的构型空间。出于效率原因，通常使用相同的样本计算一个中间状态与相邻两个中间状态的逐步差值。然而，此过程违反了不相关估计的假设，而该假设对于推导中间状态的最优序列和广泛使用的贝内特接受率估计器都是必要的。在这项工作中，我们通过变分方法推导了考虑这些相关性的具有最小均方误差的中间状态序列和相应估计器，并评估了其准确性。
