Programming the Undruggable Through AI-Designed Binders for Intrinsically Disordered Proteins
- Why IDRs have resisted drug discovery: How conformational heterogeneity, short linear motifs, and phase-separation biology place IDPs at the center of disease, yet beyond the reach of traditional modalities
- A new design paradigm for disordered targets: Deep-learning–enabled de novo binders and proteases that selectively recognize short (≥8 aa) and PTM-defined motifs within IDRs, achieving high affinity and specificity
- What programmable control unlocks: Case studies across oncology, neurodegeneration, and viral targets demonstrating inhibition, relocalization, and catalytic cleavage as new therapeutic mechanisms