Identification of C-phycocyanin-derived Peptides as Angiotensin Converting Enzyme and Dipeptidyl Peptidase IV Inhibitors via Molecular Docking and Molecular Dynamic Simulation

The objective of this study was to screen angiotensin converting enzyme (ACE) and dipeptidyl peptidase IV (DPP-IV) inhibitory peptides from simulated gastrointestinal digestion of C-phycocyanin using in silico methods.The molecular interaction and complex stability of C-phycocyanin-derived peptides with two receptors (ACE and DPP-IV) were studied.After in silico enzyme digestion, 32 unreported peptides were screened by comparing with BIOPEP-UWM and AHTPDB database, and none of them exhibited toxicity to the body based on ADMET predicted results.Moreover, four unreported peptides (LSPSW, CAR, GEF and MAAC) were predicted to have good biological activity.Molecular docking showed that the four peptides all formed hydrogen bonds and hydrophobic interactions with the key groups in ACE and DPP-IV active pockets, of which LSPSW was strongest binding peptide and supposed to be the most potential inhibitor for ACE and DPP-IV.LSPSW -ACE and LSPSW -DPP-IV systems were found to reach equilibrium within 50 ns of MD simulation according to their RMSD and energy results.In addition, the binding of LSPSW to ACE and DPP-IV caused the structure of receptor to be more compact.This study can provide valuable information for the development of C-phycocyanin-derived peptides as ACE and DPP-IV inhibitors.