Large-scale docking predicts that sORF-encoded peptides may function through protein-peptide interactions in Arabidopsis thaliana

• Published in: bioRxiv
• Main Authors: Hazarika, Rashmi, Sostaric, Nikolina, Sun, Yifeng, Vera Van Noort
• Format: Paper
• Language: English
• Published: Cold Spring Harbor Cold Spring Harbor Laboratory Press 31.05.2018
• Subjects: Binding sites; Hydrogen bonding; Hydrophobicity; Interfaces; Ligands; Open reading frames; Peptides; Proteins; Transcription
• DOI: 10.1101/335687

Several 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) in Arabidopsis thaliana remain 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 in A. thaliana, which will help in further experimental validation.