Diameter Is a Key 3D Characteristic for Assessments of Efficient Inhibitors of Protein?Protein Interactions
Diameter Is a Key 3D Characteristic for Assessments of Efficient Inhibitors of Protein?Protein Interactions
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直径是评估蛋白质有效抑制剂的关键 3D 特征？蛋白质相互作用
DOI：
10.1021/acs.jcim.0c00607
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发表时间：
2020
影响因子：
5.6
通讯作者：
Tomida Shuta
中科院分区：
文献类型：
--
作者：
Nakadai Masakazu;Tomida Shuta
蛋白质-蛋白质相互作用（PPI）界面抑制剂的三维（3D）分子描述符，包括物理化学和形状特性，已成为讨论的主题。然而，这些属性和结合自由能之间的关系还没有得到充分的研究。在这项研究中，我们专注于确定关键的三维分子描述符相关的结合自由能和/或PPI界面抑制剂的配体效率（LE）。结合自由能与圆柱形三维分子的直径（D）呈正相关，LE与D/重原子数（HAC）也呈正相关。此外，我们还发现了大环化合物的LE和D/HAC之间的相关性，这表明本研究结果可用于评估药物发现过程中大环PPI界面抑制剂的潜力。
Three-dimensional (3D) molecular descriptors, including physicochemical and shape properties, for protein–protein interaction (PPI) interface inhibitors have become a topic of discussion. However, the relationships between such properties and binding free energy have not been adequately investigated. In this study, we focused on identifying key 3D molecular descriptors related to the binding free energy and/or the ligand efficiency (LE) of PPI interface inhibitors. A positive correlation was found between the binding free energy and the diameter (D) of cylindrical 3D molecules, in addition to a correlation between LE andD/heavy atom count (HAC). In addition, we showed a correlation between LE andD/HAC for macrocyclic compounds, suggesting that the present findings could be applied during assessments of the potential of macrocyclic PPI interface inhibitors in drug discovery processes.