Taking GGAP-CPI as the reference model, as shown in Fig. (B), the model performances on AC molecules were highly correlated to the overall performances on most of protein subsets, suggesting AC molecules are abnormal samples exposing the out-of-distribution performances for CPI methods. Moreover, subsets with a lower percentage of AC data The performances of GGAP-CPI and its four variants were assessed across internal validation sets (CPI2M-main-pK i , -pK d " -pEC 50 , and -pIC 50 ) and are depicted in Fig. .