Large-scale docking predicts that sORF-encoded peptides may function through protein-peptide interactions in Arabidopsis thaliana
AbstractSeveral recent studies indicate that small Open Reading Frames (sORFs) embedded within multiple eukaryotic non-coding RNAs can be translated into bioactive peptides of up to 100 amino acids in size. However, the functional roles of the 607 Stress Induced Peptides (SIPs) previously identified from 189 Transcriptionally Active Regions (TARs) inArabidopsis thalianaremain unclear. To provide a starting point for function annotation of these peptides, we performed a large-scale prediction of peptide binding sites on protein surfaces using and coarse-grained peptide docking. The docked models were subjected to further atomistic refinement and binding energy calculations. A total of 530 peptide-protein pairs were successfully docked. In cases where a peptide encoded by a TAR is predicted to bind at a known ligand or cofactor-binding site within the protein, it can be assumed that the peptide modulates the ligand or cofactor-binding. Moreover, we predict that several peptides bind at protein-protein interfaces, which could therefore regulate the formation of the respective complexes. Protein-peptide binding analysis further revealed that peptides employ both their backbone and side chain atoms when binding to the protein, forming predominantly hydrophobic interactions and hydrogen bonds. In this study, we have generated novel predictions on the potential protein-peptide interactions inA. thaliana, which will help in further experimental validation.Author summaryDue to their small size, short peptides are difficult to find and have been ignored in genome annotations. Only recently, we have realized that these short peptides of less than 100 amino acids may actually play an important role in the cell. Currently, there are no high-throughput methods to find out what the functions of these peptides are in contrast with efforts that exist for ‘normal’proteins. In this work, we try to fill this gap by predicting with which larger proteins, the short peptides might interact to exert their function. We find that many peptides bind to pockets where normally other proteins or molecules bind. We thus think that these peptides that are induced by stress, may regulate protein-protein and protein-molecule binding. We make this information available through our database ARA-PEPs so that individual predictions can be followed up.