Weighted Equation and Rules - A Novel Concept for Evaluating Protein-Ligand Interaction
Weighted Equation and Rules - A Novel Concept for Evaluating Protein-Ligand Interaction
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DOI：
10.1080/07391102.2009.10507315
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发表时间：
2009-12-01
影响因子：
4.4
通讯作者：
Chen, Calvin Yu-Chian
中科院分区：
文献类型：
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作者：
Chen, Calvin Yu-Chian
本研究以人表皮生长因子受体2（HER 2）-配体为例，提出了一种新的蛋白质-配体相互作用评价方法，并以阴阳理论为基础对中药进行了定量分析。将来自参考文献的具有广泛活性（IC 50）的HER 2抑制剂（n = 176）用于对接程序以计算结合亲和力。对12个评分函数的对接评分与实际pIC（50）图进行回归。根据加权规则，选择每个评分函数回归分析的决定系数（R-2）和pIC（50）作为加权方程中的权重。加权评分（WS）与实际pIC（50）的R-2（0.5858）在统计学上高于共识评分（CS）（R-2 = 0.2441）。WS方法在于组合来自不同算法的评分函数以评估结合亲和力的总和，其比任何单一评分函数可以实现的更全面。通过方程计算的WS成功地显示出统计上显著的相关性，具有良好的可预测性。该方法为今后研究蛋白质与配体的相互作用及中药功能的定量分析提供了一个有说服力的虚拟筛选标准。
In this study, a novel methodology for evaluating protein-ligand interaction and quantitated the traditional Chinese medicine (TCM) by Yin-Yang theory are proposed and investigated by a case report of the human epidermal growth factor receptor 2 (HER2)-ligand. Inhibitors (n = 176) of HER2 from references with a broad range of activities (IC50) were employed to the docking program to calculate the binding affinities. The docking score of twelve scoring functions versus actual pIC(50) plot were regressed. According to the weighted rules, the coefficient of determinations (R-2) from the regression analysis of each scoring function and pIC(50) were chosen as the weights in the weighted equation. The R-2 (0.5858) of weighted score (WS) versus actual pIC(50), was statistically higher than that of the consensus score (CS) (R-2 = 0.2441). The WS method lies in combining the scoring functions from different algorithms to evaluate the sum of binding affinities that is more comprehensive than any single scoring function can achieve. The WS calculated by equation successfully shows a statically significant correlation with good predictability. Thus, this methodology might provide a persuasive virtual screening criterion to evaluate the protein-ligand interaction and quantitative analysis of the functions for Chinese medicine in the future.