We introduce a number of computationally inexpensive modifications to the MM/PBSA and MM/GBSA estimators for binding free energies, which are based on average receptor–ligand interaction energies in simulations of a noncovalent complex, to improve the treatment of entropy: second- and higher-order terms in a cumulant expansion and a confining potential on ligand external degrees of freedom. We also consider a filter for snapshots where ligands have drifted from the initial binding pose. The variations were tested on six sets of systems for which binding modes and free energies have previously been experimentally determined. For some data sets, none of the tested estimators led to results significantly correlated with measured free energies. In data sets with nontrivial correlation, a ligand RMSD cutoff of 3 Å and a second-order truncation of the cumulant expansion was found to be comparable or better than the average interaction energy by several statistical metrics.

中文翻译：

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端点结合自由能计算的简单熵项

我们对MM / PBSA和MM / GBSA估计量进行了计算上廉价的修改，以结合自由能，这是基于非共价复合物模拟中平均受体-配体相互作用能，以改善熵的处理：高阶项的累积扩展和对配体外部自由度的限制。我们还考虑了用于快照的过滤器，其中配体已从初始结合姿势漂移。在六组系统上测试了这些变化，该系统先前已通过实验确定了其结合模式和自由能。对于某些数据集，没有一个经过测试的估算器得出的结果与测得的自由能显着相关。在具有非平凡相关性的数据集中，