EnGCI: enhancing GPCR-compound interaction prediction via large molecular models and KAN network.

Background: Identifying GPCR-compound interactions (GCI) plays a significant role in drug discovery and chemogenomics. Machine learning, particularly deep learning, has become increasingly influential in this domain. Large molecular models, due to their ability to capture detailed structural and functional information, have shown promise in enhancing the predictive accuracy of downstream tasks. Consequently, exploring the performance of these models in GCI prediction, as well as evaluating their effectiveness when integrated with other deep learning models, has emerged as a compelling research area. This paper aims to investigate these challenges.

Results: This study introduces EnGCI, a novel model comprising two distinct modules. The MSBM integrates a graph isomorphism network (GIN) and a convolutional neural network (CNN) to extract features from GPCRs and compounds, respectively. These features are then processed by a Kolmogorov-Arnold network (KAN) for decision-making. The LMMBM utilizes two large-scale pre-trained models to extract features from compounds and GPCRs, and subsequently, KAN is again employed for decision-making. Each module leverages different sources of multimodal information, and their fusion enhances the overall accuracy of GPCR-compound interaction (GCI) prediction. Evaluating the EnGCI model on a rigorously curated GCI dataset, we achieved an AUC of approximately 0.89, significantly outperforming current state-of-the-art benchmark models.

Conclusions: The EnGCI model integrates two complementary modules: one that learns molecular features from scratch for the GPCR-compound interaction (GCI) prediction task, and another that extracts molecular features using pre-trained large molecular models. After further processing and integration, these multimodal information sources enable a more profound exploration and understanding of the complex interaction relationships between GPCRs and compounds. The EnGCI model offers a robust and efficient framework that enhances GCI predictive capabilities and has the potential to significantly contribute to GPCR drug discovery.