CheapNet: Cross-attention on Hierarchical representations for Efficient protein-ligand binding Affinity Prediction
Hyukjun Lim Sun Kim Sangseon Lee
Accurately predicting protein-ligand binding affinity is a critical challenge in drug discovery, crucial for understanding drug efficacy. While existing models typically rely on atom-level interactions, they often fail to capture the complex, higher-order interactions, resulting in noise and computational inefficiency. Transitioning to modeling these interactions at the cluster level is challenging because it is difficult to determine which atoms form meaningful clusters that drive the protein-ligand interactions. To address this, we propose CheapNet, a novel interaction-based model that integrates atom-level representations with hierarchical cluster-level interactions through a cross-attention mechanism. By employing differentiable pooling of atom-level embeddings, CheapNet efficiently captures essential higher-order molecular representations crucial for accurate binding predictions. Extensive evaluations demonstrate that CheapNet not only achieves state-of-the-art performance across multiple binding affinity prediction tasks but also maintains prediction accuracy with reasonable computational efficiency. The code of CheapNet is available at https://github.com/hyukjunlim/CheapNet.
Protein-Ligand Binding Affinity, Hierarchical Representation Learning, Cross-Attention Mechanism, Drug Discovery
We propose CheapNet, an interaction-based model with hierarchical representations and cross-attention for protein-ligand binding affinity prediction, achieving state-of-the-art performance across benchmarks with efficient complexity.