A Computational Investigation of Small Peptide of Methyl Jasmonate and Human Complement Factor in Ageing

Ageing contributes to the onset of various diseases. It is accompanied by malfunctioning and deterioration of the body systems. Identifying the biomarkers for the prediction, diagnosis, management, or prognosis of ageing and biological ageing was the aim of this study.

The peptide identification was done by analysing the conserved sequences in a comprehensive multiple alignment and domain annotation of the small peptide of methyl jasmonate esterase 1 (MJE1) present in the Vitis vinifera (wine grape). The discovery of biomarkers was done by annotating the RNA-Seq dataset that comprehensively sequenced the human Achilles tendon transcriptome in young and older people to identify differentially expressed genes. Followed by molecular docking, ADMET and protein-protein interactions studies. The molecular docking was performed by docking the active peptide of MJE1 with the human complement factor H (CFH) identified in the RNA-Seq data analysis.

The sequenced alignment analysis indicated high similarity (~99%) of MJE1 protein in the Vitis vinifera (wine grape), as well as some other set of plant species that also encode a gene for MJE1. The pharmacokinetics and ADMET properties of MJE1 revealed a molecular weight of 224.30 g/mol and polar surface area measured at 43.37 Ų, suggesting its adherence to Lipinski's rules of for drug likeliness; moreover, data supported MJE1 interactions with mostly nuclear receptors. Of all the annotated biomarkers in the RNA-Seq dataset analysed in this study, we prioritised the CFH for the robust data supporting its activities in ageing research and the availability of its crystalline structured. The molecular docking of MJE1 selected peptide with CFH surface identified conformational changes enacted by the surface and orientation interactions with four amino acid residues (CYS 1167, THR 1227, TRP 2 and PHE 10) of the protein.

By using computational techniques to investigate the plausible anti-ageing potential of the small peptide of MJE1 present in the Vitis vinifera, we identified a complex interaction between MJE1 and CFH. This finding necessitates further investigation in mouse, zebrafish or non-human primate model towards the understanding of anti-ageing therapy.