ArticleJournal of the American Chemical Society2023
Early Selection of the Amino Acid Alphabet Was Adaptively Shaped by Biophysical Constraints of Foldability.
Article in Journal of the American Chemical Society, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed.
- Functional abiotic metabolite assembly hypothesis for the early events in the origin of life.Nature communications · 2026Review
- Intermediate stages in the origin of metabolism at a phosphorylating hydrothermal vent.Science advances · 2026Article
- Prebiotic β-Strand Peptides May Be a Plausible Solution to the Protocell Permeability Problem.Journal of molecular evolution · 2026Review
- A highly limited amino acid library from asteroid Bennu yields wide-ranging protein folds.Nature communications · 2026Article
- Proteins Rich in Prime Mass Residues and Their Role in Cell Biology.Evolutionary bioinformatics online · 2026Article
- Prebiotically Plausible Peptides can Self-assemble into β-rich Nanostructures.bioRxiv : the preprint server for biology · 2025Article
- Protopeptide backbone affects assembly in aqueous solutions.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Folding and knotting of biotic and prebiotic amino acid sequences through reverse evolution.Biophysical journal · 2025Article
- Reduced Amino Acid Substitution Matrices Find Traces of Ancient Coding Alphabets in Modern Day Proteins.Molecular biology and evolution · 2025Article
- The Role of Mutations, Addition of Amino Acids, and Exchange of Genetic Information in the Coevolution of Primitive Coding Systems.International journal of molecular sciences · 2025Article
- In silico evolution of globular protein folds from random sequences.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Designing single-polymer-chain nanoparticles to mimic biomolecular hydration frustration.Nature chemistry · 2025Article
- The origins and evolution of translation factors.Trends in genetics : TIG · 2025Review
- Meeting Proceedings from 4th Minimal Cell Workshop: Exploring JCVI Minimal Cell Fundamental Insights and Integrative Applications.ACS synthetic biology · 2025Article
- Long-Range Electrostatics in Serine Proteases: Machine Learning-Driven Reaction Sampling Yields Insights for Enzyme Design.Journal of chemical information and modeling · 2025Article
- Similarity Analysis of Computer-Generated and Commercial Libraries for Targeted Biocompatible Coded Amino Acid Replacement.International journal of molecular sciences · 2024Article
- The interplay between peptides and RNA is critical for protoribosome compartmentalization and stability.Nucleic acids research · 2024Article
- Alkylation of Complex Glycine Precursor (CGP) as a Prebiotic Route to 20 Proteinogenic Amino Acids Synthesis.Molecules (Basel, Switzerland) · 2024Review
- Article
- Phosphoric acid salts of amino acids as a source of oligopeptides on the early Earth.Communications chemistry · 2024Article
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11 authors.
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Abstract
Whereas modern proteins rely on a quasi-universal repertoire of 20 canonical amino acids (AAs), numerous lines of evidence suggest that ancient proteins relied on a limited alphabet of 10 "early" AAs and that the 10 "late" AAs were products of biosynthetic pathways. However, many nonproteinogenic AAs were also prebiotically available, which begs two fundamental questions: Why do we have the current modern amino acid alphabet and would proteins be able to fold into globular structures as well if different amino acids comprised the genetic code? Here, we experimentally evaluate the solubility and secondary structure propensities of several prebiotically relevant amino acids in the context of synthetic combinatorial 25-mer peptide libraries. The most prebiotically abundant linear aliphatic and basic residues were incorporated along with or in place of other early amino acids to explore these alternative sequence spaces. The results show that foldability was likely a critical factor in the selection of the canonical alphabet. Unbranched aliphatic amino acids were purged from the proteinogenic alphabet despite their high prebiotic abundance because they generate polypeptides that are oversolubilized and have low packing efficiency. Surprisingly, we find that the inclusion of a short-chain basic amino acid also decreases polypeptides' secondary structure potential, for which we suggest a biophysical model. Our results support the view that, despite lacking basic residues, the early canonical alphabet was remarkably adaptive at supporting protein folding and explain why basic residues were only incorporated at a later stage of protein evolution.
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