MMSG-DTA: A Multimodal, Multiscale Model Based on Sequence and Graph Modalities for Drug-Target Affinity Prediction.

Abstract

Drug-Target Affinity (DTA) prediction is a cornerstone of drug discovery and development, providing critical insights into the intricate interactions between candidate drugs and their biological targets. Despite its importance, existing methodologies often face significant limitations in capturing comprehensive global features from molecular graphs, which are essential for accurately characterizing drug properties. Furthermore, protein feature extraction is predominantly restricted to 1D amino acid sequences, which fail to adequately represent the spatial structures and complex functional regions of proteins. These shortcomings impede the development of models capable of fully elucidating the mechanisms underlying drug-target interactions. To overcome these challenges, we propose a multimodal, multiscale model based on Sequence and Graph Modalities for Drug-Target Affinity (MMSG-DTA) Prediction. The model combines graph neural networks with Transformers to effectively capture both local node-level features and global structural features of molecular graphs. Additionally, a graph-based modality is employed to improve the extraction of protein features from amino acid sequences. To further enhance the model's performance, an attention-based feature fusion module is incorporated to integrate diverse feature types, thereby strengthening its representation capacity and robustness. We evaluated MMSG-DTA on three public benchmark data sets─Davis, KIBA, and Metz─and the experimental results demonstrate that the proposed model outperforms several state-of-the-art methods in DTA prediction. These findings highlight the effectiveness of MMSG-DTA in advancing the accuracy and robustness of drug-target interaction modeling.