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

Abstract Aspartic acid (Asp) has 2 carboxyl groups, either of which can form an amide bond. However, among the present proteins, only one is involved in a peptide bond, whereas the other is regarded as “side chain,” with only α-Asp identified as a gene-encoded amino acid residue. In this study, molecular dynamics simulations of random peptides were performed to investigate why β-Asp, which may have been present in primitive proteins in the origin of proteins, was excluded from proteinogenic amino acids. [GADV]-peptides, constructed from Gly, Ala, Asp, and Val, were used as putative primitive proteins. Molecular dynamics simulations were performed when β-Asp was used instead of Asp in the [GADV]-peptides and when β-Asp was added to the [GADV]-peptide. The secondary structures of peptides containing β-Asp were less than [GADV]-peptides, and their ability to form a protein-like structure was inferior to that of peptides excluding β-Asp. Thus, the ability to form protein-like structures may have acted as a selection pressure, leading to the elimination of protein synthesis systems utilizing β-Asp from primitive life. When the [GADVB]-peptide, i.e. a β-amino acid β-Ala, was added to the [GADV] amino acid set, the ability to form secondary structures reduced. Therefore, β-amino acids that altered the main chain length were excluded from primitive life, despite β-Ala being relatively abundant on primitive Earth.