From ancestral peptides to designed proteins
Related Experiment Video
Updated: Feb 17, 2026

Application of I TASSER, trRosetta, UCSF Chimera, HADDOCK server, and HEX loria for De Novo and In Silico Design of Proteins
Published on: July 8, 2025
1Department of Protein Evolution, Max Planck Institute for Developmental Biology, 72076 Tübingen, Germany.
Abstract:
The diversity of modern proteins arose through the combinatorial shuffling and differentiation of a limited number of autonomously folding domain prototypes, but the origin of these prototypes themselves has long remained poorly understood. In recent years, the proposal that they originated by repetition, accretion, and recombination from an ancestral set of peptides, which evolved as cofactors of RNA-based replication and catalysis, has gained wide acceptance, supported by the systematic identification of such ancestral peptides and the experimental recapitulation of the mechanisms by which they could have yielded the first folded proteins. Inspired by this evolutionary process, protein engineers have seized on design from pre-optimized peptide components as a powerful approach to generating proteins with novel topology and functionality.
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