Ramharter et al. reported the discovery of BI-3406, which is an inhibitor of protein-protein interaction (PPI) between SOS1 and KRAS. Because esp_extre represents the local pocket polarity for the substituted groups, we divided compounds 34 to 39 and compounds 40 to 43 in two groups. For compounds 34 to 39, the es-p_extre values calculated for this pocket are larger than 20.4 kcal/(mol*e) which show the pocket at this area has enough polarity. The sas_ratio of compounds 34 to 39 are 0.24, 0.38, 0.25, 0.20, 0.18, and 0.17, respectively. All of the sas_ratio indices are smaller than the default 0.35. The sas_ratio of compound 35 is 0.38, slightly over 0.35, and its EC score has the same linear correlation with activity as the others (see Figure ). For the second group, however, the sas_ratio values are 0.66, 0.67, 0.64, and 0.65 for the compounds 40 to 43, which are noticeably larger than the default of 0.35. If we exclude EC scores of high sas_ratio indices, the EC scores of the first group compounds give a good linear relationship with activity (the R 2 is 0.83 as shown in Figure ). BRD4 is a member of the BET (bromodomain and extra terminal domain) family, which is a target related to cancer and other diseases. We applied the EC scores to two literatures reported BRD4 inhibitor sets and identified no correlation between EC scores and bioactivity. We then applied esp_extre and sas_ratio to select the ligands suitable to use EC score for ranking. In the first series of compounds (Figure ), we retrieved their 3D complex (PDB id 6CKR)