Surface-based multimodal protein-ligand binding affinity prediction.

Abstract

In the field of drug discovery, accurately and effectively predicting the binding affinity between proteins and ligands is crucial for drug screening and optimization. However, current research primarily utilizes representations based on sequence or structure to predict protein-ligand binding affinity, with relatively less study on protein surface information, which is crucial for protein-ligand interactions. Moreover, when dealing with multimodal information of proteins, traditional approaches typically concatenate features from different modalities in a straightforward manner without considering the heterogeneity among them, which results in an inability to effectively exploit the complementary between modalities. We introduce a novel multimodal feature extraction (MFE) framework that, for the first time, incorporates information from protein surfaces, 3D structures, and sequences, and uses cross-attention mechanism for feature alignment between different modalities. Experimental results show that our method achieves state-of-the-art performance in predicting protein-ligand binding affinity. Furthermore, we conduct ablation studies that demonstrate the effectiveness and necessity of protein surface information and multimodal feature alignment within the framework. The source code and data are available at https://github.com/Sultans0fSwing/MFE.