A strategy based on gene sequencing and molecular docking for analysis and prediction of bioactive peptides in...

Peptides are a class of protein fragments with relatively high biological activity and intense specificity, which play crucial role in the treatment of Shuxuetong injection (SXT). However, the extraordinary complexity of Chinese medicinal formulates and the lack of systematic identification methods are primary challenges for study of pharmacodynamic peptides. In addition, infinitesimal peptides contents further hinder the identification and structural characterization of polypeptide by traditional means. In this paper, we described a strategy that LC-MS combined with molecular docking to systematically illustrate the peptide components of SXT. The key to this research was used of gene sequencing to establish a SXT protein database to further achieve the separation and enrichment of chemical methods. Moreover, the ADRA2A, PAR4 and DRD3 were precisely docked with the identified peptides. The result indicated that 12 compounds had stable binding ability and were speculated to be the latent bioactive monomers for the treatment of stroke. Additionally, 12 peptides were verified by cell-based experiment. The results showed that only YLKTT could indeed protect astrocytes from oxygen glucose deprivation/reoxygenation (OGD/R). The YLKTT showed higher activity than the others in vitro. It might be a completely new compound that has never been reported before, providing the basis for further research and a new paradigm for stroke.