Energy-entropy prediction of octanol-water logP of SAMPL7 N-acyl sulfonamide bioisosters.
Energy-entropy prediction of octanol-water logP of SAMPL7 N-acyl sulfonamide bioisosters.
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DOI：
10.1007/s10822-021-00401-w
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发表时间：
2021-07
影响因子：
3.5
通讯作者：
Henchman RH
中科院分区：
文献类型：
--
作者：
Falcioni F;Kalayan J;Henchman RH
分配系数量化分子在两个不相容的液体之间的分布。虽然计算它们的方法很多，但还没有一种方法基于每个系统的自由能来表示能量和熵，其中熵取决于系统所有量子态的概率分布。在这里，我们测试了一种称为能量熵多尺度细胞相关(EE-MCC)的方法，用于在SAMPL7物理性质挑战(蛋白质和配体建模的统计评估)中计算22个N-酰基磺胺的辛醇-水对数值。对于三个单独的计算，EE-MCC logP值与实验值的平均误差为1.8logP单位，标准误差为1.0logP单位。这些误差主要是由于获得了足够集中的能量，从而给出了准确的大数值差异，特别是对于大分子溶剂辛醇。然而，这也是一个关于熵的问题，力场和MCC理论中的近似也会导致误差。MCC的独特之处在于，它解释了系统中所有分子在所有自由度上的熵贡献。水的取向熵的增加是主要的有利的熵贡献，溶质振动和取向熵的小增加支持，但被辛醇的取向熵、两种溶剂的振动熵以及溶质的位置和构象熵的不利变化所抵消。网上版载有补充材料，可在10.1007/s10822-021-00401-w查阅。
Partition coefficients quantify a molecule’s distribution between two immiscible liquid phases. While there are many methods to compute them, there is not yet a method based on the free energy of each system in terms of energy and entropy, where entropy depends on the probability distribution of all quantum states of the system. Here we test a method in this class called Energy Entropy Multiscale Cell Correlation (EE-MCC) for the calculation of octanol–water logP values for 22 N-acyl sulfonamides in the SAMPL7 Physical Properties Challenge (Statistical Assessment of the Modelling of Proteins and Ligands). EE-MCC logP values have a mean error of 1.8 logP units versus experiment and a standard error of the mean of 1.0 logP units for three separate calculations. These errors are primarily due to getting sufficiently converged energies to give accurate differences of large numbers, particularly for the large-molecule solvent octanol. However, this is also an issue for entropy, and approximations in the force field and MCC theory also contribute to the error. Unique to MCC is that it explains the entropy contributions over all the degrees of freedom of all molecules in the system. A gain in orientational entropy of water is the main favourable entropic contribution, supported by small gains in solute vibrational and orientational entropy but offset by unfavourable changes in the orientational entropy of octanol, the vibrational entropy of both solvents, and the positional and conformational entropy of the solute. The online version contains supplementary material available at 10.1007/s10822-021-00401-w.
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影响因子：
5.5
作者：
Goetz, Andreas W.;Williamson, Mark J.;Xu, Dong;Poole, Duncan;Le Grand, Scott;Walker, Ross C.
通讯作者：
Walker, Ross C.
DOI：
10.3390/e21080750
发表时间：
2019-07-31
期刊：
Entropy (Basel, Switzerland)
影响因子：
--
作者：
Ali HS;Higham J;Henchman RH
通讯作者：
Henchman RH
影响因子：
3.4
作者：
Irudayam, Sheeba Jem;Plumb, Richard D.;Henchman, Richard H.
通讯作者：
Henchman, Richard H.
影响因子：
3
作者：
GHOSE, AK;CRIPPEN, GM
通讯作者：
CRIPPEN, GM
影响因子：
4.4
作者：
Horn, HW;Swope, WC;Head-Gordon, T
通讯作者：
Head-Gordon, T