Cocry-pred: A Dynamic Resource Propagation Method for Cocrystal Prediction.

Drug cocrystallization is a powerful strategy to enhance drug properties by modifying their physicochemical characteristics without altering their chemical structure. However, the identification of suitable coformers remains a challenging and resource-intensive task. To streamline this process, we developed a novel cocrystal prediction model, Cocry-pred, which utilizes the Network-Based Inference (NBI) algorithm─a dynamic resource propagation method─to recommend coformers for target molecules based on topological data from cocrystal network and molecular substructure information. We evaluated the impact of 13 types of molecular fingerprints and different numbers of propagation rounds on model performance. Additionally, to achieve optimal performance, we introduced three key hyperparameters─α (node weights), β (edge weights) and γ (penalty for high-degree nodes)─to balance the influence of various factors within the composite network. The best performance of Cocry-pred achieved an impressive AUC of 0.885 and an RS of 0.108. To validate the reliability of the model, we employed it to predict potential coformers for Apatinib. Subsequently, seven Apatinib cocrystals were then synthesized experimentally, among which single-crystal structures were obtained for two cocrystals. This advancement highlights the potential of Cocry-pred as a powerful tool, offering significant improvements in efficiency and providing valuable insights for cocrystal screening and design.