Targeting protein disorder using protein design and cyclic peptide screening Instabilité Génétique et Cancer

Protein disorder is abundant in biology. Many of these disordered regions are essential for cellular function, and many of these are linked to human disease. Molecules able to bind to, and modulate, disordered regions would be valuable research tools and could form the basis for future therapeutics. Yet, discovery of such molecules is highly challenging using traditional ligand- and drug- discovery methods. Here, we describe two new modalities to target disordered proteins: de novo microproteins and de novo cyclic peptides. Driven by powerful new technologies for ligand discovery: machine learning-enabled computational design and experimental screening of enormous molecular libraries, respectively. These technologies have the potential to generate much needed research ligands, and open up disordered protein biology to drug discovery

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