Prebiotically Plausible Peptides can Self-assemble into β-rich Nanostructures

Area of Science:

• Origin of Life Research
• Biochemistry
• Astrobiology

Background:

• Prebiotic Earth likely lacked abundant basic amino acids (lysine, arginine, histidine).
• Early peptides were short, statistical, and non-templated before ribosomal synthesis.
• Understanding the emergence of early proteins and enzymes is crucial for origins-of-life studies.

Purpose of the Study:

• Investigate the properties of random peptide libraries using a prebiotically plausible acidic amino acid alphabet.
• Determine if these sequences can form structures relevant to early protein evolution.
• Explore the potential for self-assembly, secondary structure, and catalytic activity in prebiotic peptides.

Main Methods:

• Synthesis of random peptide libraries spanning an electrostatic spectrum.
• Systematic interrogation of peptide properties, including secondary structure and assembly.
• Analysis of metal ion binding capabilities.
• Structural prediction using a large language model.

Main Results:

• Acidic amino acid-rich peptides exhibit strong propensity for secondary structure (β-sheets) and soluble, higher-order assembly.
• These assemblies are heterogeneous, consistent with statistical early Earth peptides, and distinct from amyloid structures.
• Acidic peptides demonstrate inherent metal ion binding capacity, suggesting catalytic potential.
• Large language model predictions indicate a propensity for compact conformations in these acidic peptides.

Conclusions:

• Unevolutionized sequences of prebiotically available acidic amino acids can readily form foldable, self-assembling polymers.
• These findings suggest a potential stepping stone towards the first proteins prior to the advent of genetic selection.
• The inherent properties of acidic peptides offer plausible solutions to key questions in the origins of life.