evo_c2001

WHAT IT IS & WHY IT MATTERS

evo_c2001 is a novel 280-residue intrinsically disordered protein (IDP) with a highly cationic, lysine-rich C-terminal block (100 lysines against 8 acidic residues) and a lysine-free portion before it that is largely hydropathy-positive. It uses only 10 of the 20 amino acids and has no aromatic residues, no cysteines and no folded domain. 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 5 transient motifs among glycine-, aliphatic- and polar-rich segments, none involving the lysine block. 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 +91.9 at pH 7.4 (pI 11.16), carried by a single block, and the isolated chain has predictable dimensions (Rg 6.37 nm, Rh 4.27 nm) that a partner can check by SAXS or DLS. The lysine-free portion carries every predicted aggregation-prone segment and every enriched intramolecular contact, giving the molecule a block-type, amphiphilic architecture whose assembly behaviour remains untested. 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