Evaluation of protein-ligand binding free energy focused on its entropic components
Evaluation of protein-ligand binding free energy focused on its entropic components
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DOI：
10.1002/jcc.22891
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发表时间：
2012-02-15
影响因子：
3
通讯作者：
Sakurai, Minoru
中科院分区：
文献类型：
--
作者：
Chiba, Shuntaro;Harano, Yuich;Sakurai, Minoru
FK 506结合蛋白-配体系统的结合自由能评估为两个熵分量之和，即结合后蛋白和配体分子的水熵增益和构型熵损失。这两个熵分量的计算使用形态热力学结合的分子液体的热力学理论和正常模式分析，分别。我们发现，有一个很好的结合自由能的计算值和实验值之间的相关性。并将计算结果与MM-PB/SA等其他几种结合自由能计算方法的计算结果进行了比较。结合可以很好地阐明两个熵组分的竞争。在蛋白质-配体结合时，可用于共存水分子的平移位移的总体积增加，导致水的可接近构型的数量增加。水熵的增加主要来源于这种效应，而水熵的增加是驱动结合的动力。该研究为蛋白质-配体结合自由能的理论预测提供了新的思路。(c)2011 Wiley Periodicals，Inc. J Comput Chem，2011年
The binding free energy for FK506-binding protein-ligand systems is evaluated as a sum of two entropic components, the water-entropy gain, and the configurational-entropy loss for the protein and ligand molecules upon the binding. The two entropic components are calculated using morphometric thermodynamics combined with a statistical-mechanical theory for molecular liquids and the normal mode analysis, respectively. We find that there is an excellent correlation between the calculated and experimental values of the binding free energy. This result is compared with those of several other binding-free energy calculation methods, including MM-PB/SA. The binding can well be elucidated by competition of the two entropic components. Upon the protein-ligand binding, the total volume available to the translational displacement of the coexisting water molecules increases, leading to an increase in the number of accessible configurations of the water. The water-entropy gain, by which the binding is driven, originates primarily from this effect. This study sheds new light on the theoretical prediction of the protein-ligand binding free energy. (c) 2011 Wiley Periodicals, Inc. J Comput Chem, 2011