evo_c2004

WHAT IT IS & WHY IT MATTERS

evo_c2004 is a novel 280-residue intrinsically disordered protein (IDP) with a highly cationic, lysine-rich C-terminal region (98 lysines against 15 acidic residues, including one uninterrupted 50-residue lysine tract) preceded by a charge-poor, largely hydropathy-positive N-terminal portion. It uses 13 of the 20 amino acids and has no aromatic residues and no folded domain; its 2 cysteines are free in the reference conformation. Sequence analysis predicts 100% disorder. A converged CALVADOS 2 simulation shows an expanded, fast-exchanging chain in solution: one free-energy basin, no evidence of discrete states and no persistent intramolecular contacts. The only enriched contacts are 4 transient motifs among glycine-, aliphatic- and polar-rich segments, none involving the long lysine tract. Throughout this dossier, REF marks the single atomistic reference conformation that seeds the simulation, ENS marks results from the simulated ensemble, and SEQ marks results computed from the sequence alone.

Strongly charged, expanded disordered chains are polymer-like building blocks whose behaviour is set largely by electrostatics, and this candidate is characterized at both ends. Its net charge is +82.8 at pH 7.4 (pI 10.72), concentrated in the C-terminal region, and the isolated chain has predictable dimensions (Rg 6.62 nm, Rh 4.41 nm) that a partner can check by SAXS or DLS. The N-terminal portion carries every enriched intramolecular contact, and no predicted aggregation-prone segment falls in the long lysine tract, giving the molecule a block-type, amphiphilic architecture whose assembly behaviour remains untested. Two cysteines and 98 lysines provide countable handles for chemistry. It has no detectable homolog in nr, no flagged structural neighbour in PDB, AlphaFold DB or ESM metagenomic databases, and no known bioactive motif, and each use case below comes with a decisive first experiment.

NOVELTY