The borderlands of foldability : lessons from simplified proteins
Seya, Koh ; Brownless, Alfie Louise R. ; Kamerlin, Shina C.L. LU
and Longo, Liam M.
(2026)
In Trends in Chemistry
8(5).
p.362-376
- Abstract
Proteins make complex life possible, yet our understanding of their emergence remains limited. What are the informational 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... (More)
Proteins make complex life possible, yet our understanding of their emergence remains limited. What are the informational 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.
(Less)
- author
- Seya, Koh
; Brownless, Alfie Louise R.
; Kamerlin, Shina C.L.
LU
and Longo, Liam M.
- organization
- publishing date
- 2026-05
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- alphabet simplification, coacervates, fold switching, prebiotic amino acids, protein evolution, protein minimization
- in
- Trends in Chemistry
- volume
- 8
- issue
- 5
- pages
- 15 pages
- publisher
- Cell Press
- external identifiers
-
- scopus:105036335770
- ISSN
- 2589-5974
- DOI
- 10.1016/j.trechm.2026.03.001
- language
- English
- LU publication?
- yes
- id
- 28b9c5eb-3032-4b46-ba8d-7f4d2718f37b
- date added to LUP
- 2026-06-26 14:46:15
- date last changed
- 2026-07-01 12:44:50
@article{28b9c5eb-3032-4b46-ba8d-7f4d2718f37b,
abstract = {{<p>Proteins make complex life possible, yet our understanding of their emergence remains limited. What are the informational 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.</p>}},
author = {{Seya, Koh and Brownless, Alfie Louise R. and Kamerlin, Shina C.L. and Longo, Liam M.}},
issn = {{2589-5974}},
keywords = {{alphabet simplification; coacervates; fold switching; prebiotic amino acids; protein evolution; protein minimization}},
language = {{eng}},
number = {{5}},
pages = {{362--376}},
publisher = {{Cell Press}},
series = {{Trends in Chemistry}},
title = {{The borderlands of foldability : lessons from simplified proteins}},
url = {{http://dx.doi.org/10.1016/j.trechm.2026.03.001}},
doi = {{10.1016/j.trechm.2026.03.001}},
volume = {{8}},
year = {{2026}},
}