Accurately computing partition coefficients is a pivotal part of drug discovery. Specifically, octanol-water partition coefficients can provide information into hydrophobicity of drug-like molecules, as well as a de facto representation of membrane permeability. However, one challenge facing the computation of partition coefficients is the need to encapsulate various microscopic environments. These include areas of largely bulk solvent (i.e., either water or octanol) or regions where octanol is saturated with water or areas of higher salt concentration. Also, tautomeric effects require consideration. Thus, we present a Boltzmann weighting approach that incorporates transfer free energies across varying microscopic media, as well as varying tautomeric state, to compute partition coefficients in the SAMPL6 challenge.

中文翻译：

---

多相玻尔兹曼加权：解决 SAMPL6 挑战中水-辛醇分配系数分子模拟中的局部不均匀性。

准确计算分配系数是药物发现的关键部分。具体来说，辛醇-水分配系数可以提供有关药物样分子疏水性的信息，以及膜渗透性的实际表示。然而，分配系数计算面临的一大挑战是需要封装各种微观环境。这些包括大量大量溶剂（即水或辛醇）的区域或辛醇被水饱和的区域或盐浓度较高的区域。此外，还需要考虑互变异构效应。因此，我们提出了一种玻尔兹曼加权方法，该方法结合了跨不同微观介质以及不同互变异构态的转移自由能，以计算 SAMPL6 挑战中的分配系数。