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Updated: Sep 28, 2026

Protein WISDOM: A Workbench for In silico De novo Design of BioMolecules
Published on: July 25, 2013
The Borderlands of Foldability: Lessons from Simplified Proteins
Koh Seya1, Alfie-Louise R Brownless2, Shina Caroline Lynn Kamerlin2,3,4
1Department of Life Science and Technology, Institute of Science Tokyo, Tokyo 152-8550, Japan.
Abstract:
Proteins make complex life possible, yet our understanding of their emergence remains limited. What are the information limits of protein folding, and how did the first proteins emerge? Protein simplification studies - in which contemporary folds are built from limited alphabets, symmetrized, fragmented, or shortened - have provided key insights into these questions. These studies use design constraints to address the discoverability of, and connectedness between, protein folds. By considering various environments, such as high salt concentrations or peptide-nucleic acid coacervates, the role of context in the emergence of folded domains is explored. Taken together, these studies support the early emergence of protein folds and reveal the existence of highly connected and readily traversable regions of sequence-structure space.
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