is exposed in the solvent but there is no strong interaction between ligand and solvent, and the EC scores work well. However, unless we know there is no strong interaction with water, which is, in many cases, unknown, it is better to apply EC score to a small sas_ratio system. From our study, 20 kcal/(mol*e) and 0.35 are the thresholds for esp_extre and sas_ratio as default setting for general application.