Bioinformatics identification and molecular mechanism of angiotensin-converting enzyme and dipeptidyl peptidase-IV inhibitory peptides from in silico digest of Crassostreagigas

As a healthy and excellent protein source, oyster has often been used for discovering peptides with diverse bioactivities via enzymatic hydrolysis. However, this procedure is time consuming and laborious. Instead, an in silico digestion process of oyster proteins was adopted in this study to simulate their digestion in the gastrointestinal tract, after which bioactivity analysis was conducted on the digest. By in silico digestion of myosin heavy chain (MHC), actin, and paramyosin of the oyster Crassostrea gigas, seventeen peptides with potential research value were identified based on the PeptideRanker score and their physical and chemical properties. ADMET analysis and bioactivity prediction revealed that 12 polypeptides had angiotensin-converting enzyme (ACE) inhibitory activity, whereas 9 polypeptides had dipeptidyl peptidase-IV (DPP-IV) inhibitory activity. Evaluation of the above 12 and 9 polypeptides suggested MMDF (Met-Met-Asp-Phe) and MR (MetArg) to have the highest predicted inhibitory activity as an ACE and DPP-IV inhibitor, respectively. Moreover, molecular docking studies showed that MMDF and MR could form stable complexes with ACE and DPP-IV proteins, respectively, with the CDOCKER energy of - 88.39 and - 76.50 kcal/mol, respectively. This study highlights the possible mechanism of the glycemia-lowering and antihypertensive activity of the oyster, and confirms the advantages of such in silico methods.