For conditions of b, c and d, we propose two indices, esp_extre and sas_ratio to help automatically recognize them. Esp_extre is the absolute extreme value of electrostatic potential on the protein surface corresponding to the polar atoms of substituent groups. A larger esp_extre value means a stronger electrostatic potential of the pocket at the area where the ligand polar atoms are. Sas_ratio refers to the ratio the substituent group exposed in the solvent in bound and unbound state, as equation ( ),