Most peptides found in nature possess homochirality, that is, they contain almost exclusively L-amino acids. Nonetheless, D-amino acids have been discovered in peptides from various organisms. This study investigated the modes of posttranslational D-amino acid incorporation in the ribosomal peptides, dermorphin and contryphan-R, through molecular modeling and molecular docking simulation techniques. The structures and interactions of the propeptides with appropriate isomerizing enzymes (racemases) were explored. Depending on the position and interaction with the bound prodermorphin, the dimeric alanine racemase adopted either a closed or an open conformation. On the other hand, regardless of the position of the procontryphan-R, a tryptophantargeting racemase with broad substrate specificity assumed only the closed conformation. Analysis of the total energies from the different interaction types involved in the enzyme-substrate models revealed that the total energy present in the dimeric configuration of the racemase was reduced in the presence of the propeptide. A complex combination of these interactions occurred at specific racemase conformations, which suggest possible energy tradeoffs associated with the association of the racemase and the propeptide. These conformational changes may represent different mechanisms through which different racemases may act on specific substrates. Analysis of the structural bases for the D-amino acid incorporation provides insights into the rare occurrence of these non-proteinogenic amino acids in peptides. The post-translational L-to Damino acid isomerization process may be further explored for the functional benefits that it offers, including its application for the development of novel peptide-based therapies.

Proteomics is an advanced approach that aims to characterize a large number of proteins (proteome) in a single assay, or single experiment.As opposed to single protein analysis using antibodybased techniques, such as western blotting, enzyme-linked immunosorbent assay (ELISA) and fluorescent microscopy, proteomics offers a valuable opportunity to study proteins "in bulk" in order to draw a clearer picture of the molecular biology of healthy and/or diseased cells.This review discusses the fundamentals of proteomics with respect to proteome complexity, reducing sample complexity by fractionation and separation methods, and protein identification based on peptide-mass and/or amino acid sequence.This review also presents a number of common proteomics workflows, the combination of some of which is likely to reveal larger proteome coverage.Both proteomics and transcriptomics enable researchers to comprehensively study the dynamic biological activities of living cells.However, each one of them has its limitations and advantages; therefore, combining the two approaches has the potential to better elucidate cellular biological processes.