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Molecules
2022 Jun 16;2712:. doi: 10.3390/molecules27123864.
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Seafood Paramyosins as Sources of Anti-Angiotensin-Converting-Enzyme and Anti-Dipeptidyl-Peptidase Peptides after Gastrointestinal Digestion: A Cheminformatic Investigation.
Chai TT
,
Wong CC
,
Sabri MZ
,
Wong FC
.
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Paramyosins, muscle proteins occurring exclusively in invertebrates, are abundant in seafoods. The potential of seafood paramyosins (SP) as sources of anti-angiotensin-converting-enzyme (ACE) and anti-dipeptidyl-peptidase (DPP-IV) peptides is underexplored. This in silico study investigated the release of anti-ACE and anti-DPP-IV peptides from SP after gastrointestinal (GI) digestion. We focused on SP of the common octopus, Humboldt squid, Japanese abalone, Japanese scallop, Mediterranean mussel, Pacific oyster, sea cucumber, and Whiteleg shrimp. SP protein sequences were digested on BIOPEP-UWM, followed by identification of known anti-ACE and anti-DPP-IV peptides liberated. Upon screening for high-GI-absorption, non-allergenicity, and non-toxicity, shortlisted peptides were analyzed via molecular docking and dynamic to elucidate mechanisms of interactions with ACE and DPP-IV. Potential novel anti-ACE and anti-DPP-IV peptides were predicted by SwissTargetPrediction. Physicochemical and pharmacokinetics of peptides were predicted with SwissADME. GI digestion liberated 2853 fragments from SP. This comprised 26 known anti-ACE and 53 anti-DPP-IV peptides exhibiting high-GI-absorption, non-allergenicity, and non-toxicity. SwissTargetPrediction predicted three putative anti-ACE (GIL, DL, AK) and one putative anti-DPP-IV (IAL) peptides. Molecular docking found most of the anti-ACE peptides may be non-competitive inhibitors, whereas all anti-DPP-IV peptides likely competitive inhibitors. Twenty-five nanoseconds molecular dynamics simulation suggests the stability of these screened peptides, including the three predicted anti-ACE and one predicted anti-DPP-IV peptides. Seven dipeptides resembling approved oral-bioavailable peptide drugs in physicochemical and pharmacokinetic properties were revealed: AY, CF, EF, TF, TY, VF, and VY. In conclusion, our study presented in silico evidence for SP being a promising source of bioavailable and safe anti-ACE and anti-DPP-IV peptides following GI digestions.
Figure 1. Distribution of peptides of different lengths released by in silico GI digestion of seafood paramyosins. An individual amino acid released from in silico GI digestion was counted as one fragment.
Figure 2. All-atom root mean square deviation (RMSD) of (a) Free ACE and ACE-peptide complexes (b) Free DPP-IV and DPP-IV-peptide complexes during 25 ns of the molecular dynamics simulation.
Figure 3. All-atom root mean square deviation (RMSD) of (a) ACE-docked peptide complexes (b) DPP-IV-docked peptide complexes during 25 ns of the molecular dynamics simulation.
Figure 4. Snapshot of the superimposed structures of ACE in complex with peptide (a) BPPb, (b) VY, (c) AK and (d) GIL. Structures were obtained from the trajectory file in the interval of 5 ns for 25 ns MD.
Figure 5. Snapshot of the superimposed structures of DPP-IV in complex with peptide (a) Diprotin A, (b) TF, (c) TY, (d) VF, (e) VY and (f) IAL. Structures were obtained from the trajectory file in the interval of 5 ns for 25 ns.
Figure 6. All-atom radius of gyration of (a) ACE and (b) DPP-IV as free proteins and forming complexes with the inhibitor peptides during 25 ns of the molecular dynamics simulation period.
Figure 7. (a) Total number of hydrogen bonds interactions between ACE and each peptide and (b) intermolecular distance of ACE with peptides during 25 ns of the molecular dynamics simulation period.
Figure 8. (a) Total number of hydrogen bonds interactions between DPP-IV and each peptide and (b) intermolecular distance of DPP-IV with peptides during 25 ns of the molecular dynamics simulation period.
Figure 9. Seven putative drug-like peptides derived from seafood paramyosins.
