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

Abstract

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.

Prediction of DPP‐IV inhibitory potentials of polyphenols existed in Qingke barley fresh noodles: In vitro and in silico analyses

“…The DPP‐IV inhibition activity of C‐phycocyanin‐derived peptides has been predicted using the molecular docking and molecular dynamics simulation method. Molecular docking showed that four C‐phycocyanin‐derived peptides including LSPSW, CAR, GEF, and MAAC formed hydrogen bonds and hydrophobic interactions with the active pockets of the DPP‐IV, and inhibited its enzyme activity, of which LSPSW showed a strong inhibition activity (Pan, Zhou, et al, 2020). Araki et al revealed the DPP‐IV inhibition mechanism of tripeptides was revealed by molecular docking (Araki et al, 2020).…”

In silico analysis of novel dipeptidyl peptidase-IV inhibitory peptides released from Macadamia integrifolia antimicrobial protein 2 (MiAMP2) and the possible pathways involved in diabetes protection

“…Inhibition of DPP-IV activity leads to increased levels of plasma GLP-1 and insulin, and thereby lowers blood glucose levels. The activity of DPP-IV is closely related to its three active sites, namely S1 (Tyr547, Ser630, Tyr631, Val656, Trp659, Tyr662, Tyr666, Asn710, Val711 and His740), S2 (Glu205, Glu206, Tyr662) and S3 (Ser209, Arg358 and Phe357) pockets ( Pan et al, 2020 ). Therefore, S1, S2 and S3 pockets were selected as docking targets to screen DPP-IV inhibitory peptides preliminarily.…”

“…2 . Root mean square deviation (RMSD) is used to measure the difference in conformation for each frame in a MD trajectory with a reference structure ( Pan et al, 2020 ). Fig.…”

Conformational-specific self-assembled peptides as dual-mode, multi-target inhibitors and detectors for different amyloid proteins

“…However, almost all amyloid-binding ligands still possess either property, i.e., amyloid detectors do not function as amyloid inhibitors, and vice versa. Different from conventional amyloid-binding ligands (e.g., antibodies, 3,4 polymers, 5,6 nanoparticles, [7][8][9] organic molecules, 10,11 and drugs 12,13 ), small peptides, [14][15][16][17] despite being less explored, are developed as highly sensitive and specific binding molecules for either inhibiting or detecting amyloid proteins, due to several intrinsic advantages of small sizes for mass production at low cost, ease of sequence/structural modifications to realize high bioactivity, and less susceptibility to proteolytic degradation. However, challenges still largely remain for developing peptide-based amyloid inhibitors or detectors.…”