evo_c2307

WHAT IT IS & WHY IT MATTERS

evo_c2307 is a novel 280-residue intrinsically disordered protein (IDP) built mainly from glycine (93), proline (62) and alanine (59), which together make up 214 of its 280 residues. It uses 16 of the 20 amino acids, carries only 15 charged residues (net charge −3.4 at pH 7.4, pI 4.27) and a single aromatic residue, and has no folded domain. Sequence analysis predicts 100% disorder, and no structure predictor places it with confidence: ESMFold gives a mean pLDDT of 49.2. 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, with only 2 of 37,128 residue pairs individually enriched and no interaction motif. 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.

Long, flexible, low-interaction disordered chains are useful polymer-like parts, and this candidate is characterized at both ends. Its charge is low (FCR 0.054) and it has one aromatic residue, so it has few of the electrostatic or aromatic interactions that make disordered chains sticky, and no intramolecular contact is persistent in the ensemble. The isolated chain has predictable dimensions (Rg 4.74 nm, Rh 3.57 nm; Rg matches the typical-IDP reference, ratio 1.00) 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 a state-of-the-art predictor cannot place it. Two segments are flagged as aggregation-prone by sequence predictors and remain to be tested. Each use case below comes with a decisive first experiment.

NOVELTY