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

Abstract

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 functional annotation of these plant-derived peptides, we performed a large-scale prediction of peptide binding sites on protein surfaces using 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.

Molecular Docking: Shifting Paradigms in Drug Discovery

“…For example, thanks to the improved speed and prediction power, docking has also been embedded into large-scale screening protocols to identify [60], e.g. : (i) protein binding sites in which ligands could bind [61]; (ii) novel molecular targets of known ligands [54]; (iii) potential adverse drug reactions (ADRs) [62], and; (iv) ligands with novel chemotypes active against a given target or a set of desired targets [55].…”

Identification of Microproteins in Saccharomyces cerevisiae under Different Stress Conditions

“…Environmental stress tolerance varies widely according to the species (genome), cell type, and differentiation state (proteome). Growing evidence has shown that microproteins can play an essential role in the stress response of prokaryotes and eukaryotes. , …”

“…Growing evidence has shown that microproteins can play an essential role in the stress response of prokaryotes and eukaryotes. 4,5 Small open reading frame-encoded peptides (SEPs) are microproteins of less than 100−150 amino acids (AA), which are widely distributed in different species (yeast, 6 Drosophila, 7 mice, 8 human, 9 plants, 10 etc.) and play crucial roles in transcriptional regulation, metabolism, cell growth and development, tumorigenesis, calcium transport, and stress response.…”

Discovery and in vitro Evaluation of Novel Serotonin 5‐HT2A Receptor Ligands Identified Through Virtual Screening

“…High‐resolution mass spectra (HRMS) were acquired on a Bruker microTOF−Q II mass spectrometer with electrospray ionization (ESI), whereas the HPLC analysis was performed on a Dionex Ultimate 3000 RS system equipped with Kinetex PS−C18 100×2.1 column, and generic 20 %–100 % MeCN in water gradient. Fragment analysis was performed using Canvas 4.2 software [51] . Moreover, similarity analysis was performed using Python (v.3.9.7) and the Rdkit library (v.2022.09.3).…”

“…Fragment analysis was performed using Canvas 4.2 software. [51] Moreover, similarity analysis was performed using Python (v.3.9.7) and the Rdkit library (v.2022.09.3). The identified compounds were compared to all known ligands of the 5-HT 2A receptor, downloaded from ChEMBL, using the Tanimoto coefficient based on MACCS 2D fingerprints.…”