evo_c2110

WHAT IT IS & WHY IT MATTERS

evo_c2110 is a novel 280-residue intrinsically disordered protein (IDP) with a highly cationic, lysine-rich block (86 lysines and 6 arginines against 23 acidic residues) and a more mixed remainder rich in glycine (40) and proline (30). It uses 17 of the 20 amino acids (no methionine, histidine or tryptophan), carries 8 cysteines (1 disulfide in the reference conformation, 6 free) and 11 aromatic residues, and has no stable fold. 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 4 enriched contact motifs are transient; the only one with a clear electrostatic character pairs an acidic segment with 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 adds chemically addressable handles. Its net charge is +68.3 at pH 7.4 (pI 10.28), organised mainly in one block, and the isolated chain has predictable dimensions (Rg 5.52 nm, Rh 3.91 nm) that a partner can check by SAXS or DLS. Six free cysteines and 86 lysines provide thiol and amine chemistry for crosslinking, conjugation and grafting, and the predicted aggregation-prone segments lie outside the cationic block, which makes the molecule a candidate for directed assembly. It has no detectable homolog in nr, no flagged structural neighbour in PDB, AlphaFold DB or ESM metagenomic databases, and ESMFold returns a low-confidence model (mean pLDDT 47.06), so a current AI structure predictor does not resolve it. Each use case below comes with a decisive first experiment.

NOVELTY