PCIM-DTA: Pairwise Conditional Interaction Modeling for Drug-Target Affinity Prediction under Cold-Start Scenarios.

Abstract

MOTIVATION Cold-start drug-target affinity prediction remains challenging because static interaction mechanisms cannot adapt to individual drug-target pairs. RESULTS We propose PCIM-DTA, which constructs pair-level interaction representations and derives a pair-specific condition vector from global drug and target features. The condition vector modulates attention, pair-token features, distribution-aware recalibration, and regression parameters, while graph message passing captures higher-order dependencies. Experiments on Davis and BindingDB-Kd show that PCIM-DTA achieves competitive or superior performance under Warm, Cold-drug, Cold-target, Cold-both, and Scaffold-drug settings. Ablation studies support the contribution of each component. AVAILABILITY AND IMPLEMENTATION The datasets used in this study are publicly available, including the Davis and BindingDB-Kd datasets. The implementation code of PCIM-DTA is publicly available at https://github.com/1322469934/PCIM-DTA. SUPPLEMENTARY INFORMATION Supplementary data are available at Bioinformatics online.