Molecular dynamics simulations of putative primitive proteins including β-aspartic acid residues.

This article investigates why β-aspartic acid (β-Asp) residues were excluded from proteinogenic amino acids during early protein evolution, focusing on putative primitive proteins composed of Glycine (G), Alanine (A), Aspartic acid (D), and Valine (V), known as [GADV]-peptides. Using molecular dynamics simulations, the study compares peptides containing α-Asp, β-Asp, and β-amino acids such as β-alanine (β-Ala), assessing their abilities to form secondary (helix) and rigid protein-like structures. Results show that peptides with β-Asp or β-Ala exhibit significantly reduced secondary structure formation and rigidity compared to those with only α-Asp, suggesting that the capacity to form stable protein-like structures acted as a selection pressure favoring α-Asp incorporation in primitive proteins. The findings imply that structural constraints, rather than mere availability, influenced the exclusion of β-amino acids like β-Asp and β-Ala from the canonical set of proteinogenic amino acids during the origin of life.