On the primitive Earth, both l- and d-amino acids would have been present. However, only l-amino acids are essential blocks to construct proteins in modern life. To study the relative stability of d-amino acid substituted peptides, a variety of computational methods were applied. Ten prebiotic amino acids (Gly, Ala, Asp, Glu, Ile, Leu, Pro, Ser, Thr, and Val) were previously determined by multiple meteorite, spark discharge, and hydrothermal vent studies. Some previously reported early Earth polypeptide analogs were focused on in this study. Tripeptides composed of only Asp, Ser, and Val exemplified that different positions (i.e., N-terminus, C-terminus, and middle) made a difference in the minimal folding energy of peptides, while the chemical classification of amino acid (hydrophobic, acidic, or hydroxylic) did not show a significant difference. Hierarchical cluster analysis for dipeptides with all possible combinations of the proposed ten prebiotic amino acids and their d-amino acid substituted derivatives generated five clusters. Primordial simple polypeptides were modeled to test the significance of molecular fluctuations, secondary structure occupancies, and folding energy differences based on these clusters. We found peptides with α-helices, long β-sheets, and long loops are usually less sensitive to d-amino acid replacements in comparison to short β-sheets. Intriguingly, amongst 129 d-amino acid residues, mutation sensitivity profiles presented that the ratio of more to less stable residues was about 1. In conclusion, some combinations of a mixture of l- and d-amino acids can potentially act as essential building blocks of life.

在原始地球上，l - 和d - 氨基酸都会存在。然而，只有l-氨基酸是现代生活中构建蛋白质的必需成分。研究d的相对稳定性-氨基酸取代的肽，应用了多种计算方法。十种益生元氨基酸（Gly、Ala、Asp、Glu、Ile、Leu、Pro、Ser、Thr 和 Val）先前已通过多次陨石、火花放电和热液喷口研究确定。本研究重点关注一些先前报道的早期地球多肽类似物。仅由 Asp、Ser 和 Val 组成的三肽举例说明不同位置（即 N 端、C 端和中间）使肽的最小折叠能有所不同，而氨基酸的化学分类（疏水性、酸性，或羟基）没有显示出显着差异。具有提议的十种益生元氨基酸及其d的所有可能组合的二肽的分层聚类分析-氨基酸取代的衍生物产生五个簇。对原始简单多肽进行建模以测试基于这些簇的分子波动、二级结构占据和折叠能量差异的显着性。我们发现与短 β-折叠相比，具有 α-螺旋、长 β-折叠和长环的肽通常对d-氨基酸置换不太敏感。有趣的是，在 129 个d-氨基酸残基中，突变敏感性图谱表明，稳定性较高的残基与较不稳定的残基的比率约为 1。总之，l-和d-氨基酸混合物的某些组合可能充当基本的构建块的生活。