GPCNDTA: Prediction of drug-target binding affinity through cross-attention networks augmented with graph features and pharmacophores

Drug-target affinity prediction is a challenging task in drug discovery. The latest computational models have limitations in mining edge information in molecule graphs, accessing to knowledge in pharmacophores, integrating multimodal data of the same biomolecule and realizing effective interactions between two different biomolecules. To solve these problems, we proposed a method called Graph features and Pharmacophores augmented Cross-attention Networks based Drug-Target binding Affinity prediction (GPCNDTA). First, we utilized the GNN module, the linear projection unit and self-attention layer to correspondingly extract features of drugs and proteins. Second, we devised intramolecular and intermolecular cross-attention to respectively fuse and interact features of drugs and proteins. Finally, the linear projection unit was applied to gain final features of drugs and proteins, and the Multi-Layer Perceptron was employed to predict drug-target binding affinity. Three major innovations of GPCNDTA are as follows: (i) developing the residual CensNet and the residual EW-GCN to correspondingly extract features of drug and protein graphs, (ii) regarding pharmacophores as a new type of priors to heighten drug-target affinity prediction performance, and (iii) devising intramolecular and intermolecular cross-attention, in which the intramolecular cross-attention realizes the effective fusion of different modal data related to the same biomolecule, and the intermolecular cross-attention fulfills the information interaction between two different biomolecules in attention space. The test results on five benchmark datasets imply that GPCNDTA achieves the best performance compared with state-of-the-art computational models. Besides, relying on ablation experiments, we proved effectiveness of GNN modules, pharmacophores and two cross-attention strategies in improving the prediction accuracy, stability and reliability of GPCNDA. In case studies, we applied GPCNDTA to predict binding affinities between 3C-like proteinase and 185 drugs, and observed that most binding affinities predicted by GPCNDTA are close to corresponding experimental measurements.