Exploiting Pre-trained Models for Drug Target Affinity Prediction with Nearest Neighbors

Drug-Target binding Affinity (DTA) prediction is essential for drug discovery. Despite the application of deep learning methods to DTA prediction, the achieved accuracy remain suboptimal. In this work, inspired by the recent success of retrieval methods, we propose kNN-DTA, a non-parametric embedding-based retrieval method adopted on a pre-trained DTA prediction model, which can extend the power of the DTA model with no or negligible cost. Different from existing methods, we introduce two neighbor aggregation ways from both embedding space and label space that are integrated into a unified framework. Specifically, we propose a label aggregation with pair-wise retrieval and a representation aggregation with point-wise retrieval of the nearest neighbors. This method executes in the inference phase and can efficiently boost the DTA prediction performance with no training cost. In addition, we propose an extension, Ada-kNN-DTA, an instance-wise and adaptive aggregation with lightweight learning. Results on four benchmark datasets show that kNN-DTA brings significant improvements, outperforming previous state-of-the-art (SOTA) results, e.g, on BindingDB IC50 and Ki testbeds, kNN-DTA obtains new records of RMSE bf0.684 and bf0.750. The extended Ada-kNN-DTA further improves the performance to be bf0.675 and bf0.735 RMSE. These results strongly prove the effectiveness of our method. Results in other settings and comprehensive studies/analyses also show the great potential of our kNN-DTA approach.