Integrating multimodal features with deep learning for protein solubility prediction

Protein solubility prediction holds significant importance in the fields of biotechnology and medicine. With the continual advancements of computational and experimental techniques such as protein design, enzyme mining, and directed evolution, accurate prediction of native and mutant protein solubility has become a key step in accelerating the development of functional proteins. In this study, we extracted physicochemical properties and co-evolutionary features from protein sequences, and further incorporated graph-based protein representations along with surface features as inputs for solubility prediction. Building upon these features, we developed two models, ProSolNet and ProSolNet_Mut. ProSolNet predicts whether a protein is soluble, while ProSolNet_Mut predicts solubility changes induced by mutations. Compared with state-of-the-art models, both models achieved higher accuracy in their respective tasks. In addition, we investigated the underlying mechanisms and application potential of the models through interpretability analysis.