Implicit ligand theory for relative binding free energies: II. An estimator based on control variates.
Implicit ligand theory for relative binding free energies: II. An estimator based on control variates.
复制标题
相对结合自由能的隐式配体理论：II。
DOI：
10.1088/2399-6528/abcbac
复制
发表时间：
2020
影响因子：
1.2
通讯作者：
Minh,DavidDL
中科院分区：
文献类型：
--
作者：
Nguyen,TrungHai;Minh,DavidDL
隐式配体理论描述了配体与多种刚性受体构象的非共价结合自由能和结合自由能之间的关系。我们以前已经表明，如果受体构象的采样或重新加权的全息合奏，相对于定义合奏的配体的结合自由能可以计算。在这里，我们应用方差减少技术称为控制变量，以获得一个新的相对结合自由能的统计估计。在6个参考配体和18个测试配体的数据集的应用中，对于大多数系统，未观察到估计量之间的统计学显著差异。然而，在观察到这种差异的情况下，新的估计量更准确，更精确，收敛更快。当控制变量和被平均的统计量之间存在明显的相关性（相关系数大于0.3）时，性能改善最为一致。
Implicit ligand theory describes the relationship between the noncovalent binding free energy and the binding free energy between a ligand and multiple rigid receptor conformations. We have previously shown that if the receptor conformations are sampled from or reweighed to a holo ensemble, the binding free energy relative to the ligand that defines the ensemble can be calculated. Here, we apply a variance reduction technique known as control variates to derive a new statistical estimator for the relative binding free energy. In applications to a data set of 6 reference ligands and 18 test ligands, statistically significant differences between the estimators are not observed for most systems. However, in cases where such differences are observed, the new estimator is more accurate, precise, and converges more quickly. Performance improvements are most consistent where there is a clear correlation, with a correlation coefficient greater than 0.3, between the control variate and the statistic being averaged.