Computational Studies of Fish Protein Hydrolysates as Human Angiotensin I-Converting Enzyme Inhibitors

Objectives Hypertension is an all-too-common ailment affecting countless individuals around the world. Its high prevalence underscores the need for innovative solutions, and this study delves into a promising avenue: harnessing the power of bioactive peptides to combat hypertension by inhibiting angiotensin-I converting enzyme (ACE-I). Our investigation primarily focuses on in silico analysis, evaluating the renowned human ACE-I inhibitory drug, captopril, alongside a dozen low-molecular-weight peptides derived from fish products, all with the aim of identifying potent ACE inhibitors. Material and Methods We carried out a comprehensive analysis of molecular docking, the assessment of absorption, distribution, metabolism, excretion, and toxicity (ADMET) drug-likeness properties, molecular mechanics/generalized born surface area (MM/GBSA) analysis, and an insightful molecular dynamics study. These peptides adhere to Lipinski’s five fundamental rules for drug-like compounds. Results Among this select group, a tripeptide ALA-ARG-SER, showcased a remarkable binding affinity of -104.34 kcal/mol with human ACE-I, outperforming the standard drug, captopril. Further, we carried out a 200 ns molecular dynamics simulation, allowing us to scrutinise the intricate interactions between the ALA-ARG-SER peptide and human ACE-I protein. Conclusion Our in silico investigation suggests that ALA-ARG-SER emerges as a strong contender and a prime candidate for inhibiting ACE. Future wet-lab trials could transform this promising peptide into a challenging drug against hypertension.