As shown in Table , the average ROC-AUC scores of the baseline models on the internal dataset for the GPCR and kinase families were 0.9140 and 0.9175, respectively. By applying our self-training method to the imbalanced data, the sizes of the positive and negative samples were progressively approximated and the ratio of positive samples in each protein converged asymptotically to 0.5 toward the final iteration (Figure ). The model trained with the updated data showed a slightly better performance based on the ROC-AUC scores of GPCR (0.9316) and kinase (0.9336). This improvement can be attributed to the expanded data distribution and resolved data imbalance. The performance of our method was better than that of the Random Negative models (GPCR: 0.9034 and kinase: 0.9053). This improvement was expected because the generated samples based on the predictive scores would be more credible than the randomly paired negative samples. Our models also outperformed Random Undersampling and Weighted Loss (Table ). These results demonstrated that our self-training method can significantly improve model robustness on external datasets. It should be noted that our method is not biased toward negative predictions because the prediction performance on the BindingDB datasets, which are dominated by positive interactions, was not compromised (ROC-AUC, PR-AUC: 0.7781, 0.9520 for GPCR and 0.8009, 0.9606 for kinase) (Figure ). We further analyzed the model's generalizability by evaluating its predictive performance at the protein level using the Davis dataset. As shown in Figure , the medians of the PR-AUC scores for the baseline model, Random Negative, and our model were 0.4888, 0.5426, and 0.6253, respectively. We separately evaluated the prediction performance for both seen and unseen proteins, which were stratified according to their presence in the training dataset (ChEMBL). The average PR-AUC scores of the baseline model, Random Negative, and our model for unseen proteins were 0.4504, 0.4877, and 0.5573, respectively, while those of the seen proteins were 0.4975, 0.6658, and 0.7144,