Thus demonstrating that the new EC scores have higher differentiation power in weaker electrostatic environments. The differentiation power of the new EC scores can be exemplified in compound 15, which has the highest local and total EC scores based on the modified EC calculation and gave the highest bioactivity in this series. In the case of angiokinase inhibition, the structure-activity relationship (SAR) of 6-substituted indolinone compounds are multifaceted, and both hydrophobic and electrostatic interactions play a significant role in their activity. We investigated whether our EC score function can guide the activity on this series. The SAR of analogs involved in the study is listed in Figure . The pocket of 6-substitutents of the analogs reside has a unique ESP surface, neutral in the middle, and polar in the bottom (the polarity comes from L868 and E885). Thus, lipophilic and electrostatic complements are both playing an important role for activity. According to our equation (1), at the relatively neutral area of pocket, small polarity of the ligand could generate higher local EC score than the ligand with large polarity. This is showcased for compound 20 and compound 24, which gave the two highest total EC scores (0.527 and 0.489) and is consistent with their highest activity in this series. The new EC scores have moderate relationship with activity, 0.45 R 2 coefficient, while Pearson's R coefficient gave no correlation (Fig. ). Such a moderate R 2 coefficient is reasonable because there are other factors like steric interaction and hydrophobic interaction play a more dominant role in activity as discussed in the original literature. This case demonstrates the usefulness of the new EC scores in more difficult cases, such as neutral pockets, where conventional EC scores usually fail. We further explored the EC score function in phosphopantetheine adenylyltransferase (PPAT, Fig. ). From Figure , It is clear that new EC scores also have better correlation with bioactivity than Pearson's R coefficients. A crystal water connects ligand and N106 was found important.