Adaptive Self-Attention Graph Pooling for Drug–Target Affinity Prediction

Abstract

Drug–target affinity (DTA) prediction is a critical step in drug discovery and precision medicine. Although graph neural networks (GNNs) have achieved remarkable progress, existing graph pooling methods rely on fixed ratios, failing to adapt to the structural diversity of molecules and proteins, which leads to information loss or redundant feature retention. To address this issue, we propose the Adaptive Self-Attention Graph Pooling (ASAGPooling) mechanism, which introduces a learnable pooling ratio that dynamically adjusts node retention during training. Furthermore, we develop ASAG-DTA, a multi-modal framework that integrates GNNs with Transformers to jointly model molecular graphs, protein contact maps, SMILES sequences, and FASTA sequences. While ASAGPooling achieves competitive prediction accuracy (MSE = 0.186 on Davis), we acknowledge that it does not surpass the state-of-the-art DynHeter-DTA (MSE = 0.130), which incorporates a more complex dynamic heterogeneous graph architecture. Instead, the key contribution of ASAGPooling lies in its adaptability, interpretability, and computational efficiency. It can eliminate the need for manually tuned pooling ratios, enable direct visualization of retained key residues/atoms, and reduce model complexity. This makes ASAG-DTA a practical lightweight alternative for large-scale virtual screening scenarios where computational resources are constrained.