evo_c1006M

WHAT IT IS & WHY IT MATTERS

evo_c1006M is a novel 376-residue intrinsically disordered protein (IDP) built as a polycation: lysine (100+ residues) diluted with glycine, leucine, glutamate and proline, and using only 14 of the 20 amino acids. It has no aromatic residues, no histidine, methionine or glutamine, 2 cysteines and no folded domain. Sequence analysis predicts 100% disorder. A converged CALVADOS 2 simulation shows a compact-leaning, fast-exchanging polyampholyte in solution: one free-energy basin, no evidence of discrete states and no persistent intramolecular contacts. The 13 enriched contact motifs are transient and mostly link an acidic stretch to lysine-rich regions; the rest are short-lived contacts within the glycine/alanine-containing portion. 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.

Poly-L-lysine is the standard polycation, but a long lysine homopolymer carries a very high charge density. evo_c1006M keeps the cationic function (net charge +59.8 at pH 7.4, pI 10.06) and dilutes it with residues chosen for flexibility, hydrophobic anchoring, internal charge balance and a disordered backbone, which is the textbook route to a lower-toxicity polycation. That rationale is not yet measured, but the simulation is consistent with it: the chain stays coiled, charge pairing is transient and the isolated chain has predictable dimensions (Rg 4.88 nm, Rh 3.95 nm) that a partner can check by SAXS or DLS. 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