Subtimizer: Computational Workflow for Structure-Guided Design of Potent and Selective Kinase Peptide Substrates

), indicating improved enzyme-substrate affinity. Designed peptides for MET and ROS1 exhibited reciprocal selectivity, with 4-fold and 11-fold preferences for their intended targets, respectively. This study demonstrates AI-driven structure-guided protein design as an effective approach for developing potent and selective kinase substrates, facilitating assay development for drug discovery and functional investigation of the kinome.