Weighted Equation and Rules - A Novel Concept for Evaluating Protein-Ligand Interaction

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.