Abstract
The stickers-and-spacers model assigns aromatic residues as the primary drivers of IDP phase separation, predicting that aromatics also occupy topologically central hub positions in IDP contact networks. Analysing a proteome-wide simulation dataset spanning six taxa, we find that charged residues, not aromatics, are the universal network hubs, with glutamate the strongest hub in every taxon and aromatics predominantly anti-hub. All IDP contact networks are universally positively assortative, a sequence-encoded topological law in which hub identity is positionally encoded. That hub character requires charge-carrier geometry rather than charge alone is demonstrated by a natural experiment in which arginine and lysine carry identical net charge yet arginine is a universal hub while lysine is a near-neutral spacer (Cohen’s
d
= 2.456), confirmed by force-field cross-validation and wet-lab condensate miscibility data. Charge-matched
α
-synuclein K→R slab simulations reveal that hub character governs condensate density and thermodynamic stability without altering the nucleation threshold, connecting single-chain topology to multi-chain phase thermodynamics. Tyrosine hub character tracks the prokaryote–eukaryote boundary, with evolutionary encoding the only explanation to survive direct testing. Together, these results establish hub identity and sticker identity as complementary organisational principles of disordered sequences, governed by distinct residue chemistries and shaped independently by selection.