The emergence of novel versus known three-dimensional structures from random sequences.

Random ~120-residue sequences built from 5–60-residue repeats frequently fold into high-confidence structures, including β-solenoids and a new α-helical screw, especially for repeats under 30 residues.

• Why it matters: The work tests whether repeated random sequences can access stable protein-like folds, addressing how “dark matter” structure space might be reachable during molecular evolution.
• What they did: Using structure prediction on ~120-residue sequences containing 5- to 60-residue random repeats, the study assessed foldability and then experimentally validated a newly observed α-helical screw by circular dichroism and X-ray crystallography.
• The result: For repeats under 30 residues, 1–12% of sequences folded with high confidence; beyond 40-residue repeats, very few were predicted to fold, implying limited discovery of novel structures without greater sampling.