# Characterization of Novel ACE-Inhibitory Peptides from Nemopilema nomurai Jellyfish Venom Hydrolysate: In Vitro and In Silico Approaches

## TL;DR

Researchers characterized two new peptides from jellyfish venom that inhibit ACE, a key enzyme in blood pressure regulation, using both lab experiments and computer simulations.

## Contribution

The study introduces two novel ACE-inhibitory peptides from Nemopilema nomurai jellyfish venom and provides detailed biochemical and computational analysis of their inhibitory mechanisms.

## Key findings

- IVGRPLANG and IGDEPRHQYL act as competitive ACE inhibitors with IC50 values of 23.81 µM and 5.68 µM, respectively.
- Molecular dynamics simulations confirmed the structural stability of ACE–peptide complexes.
- Network pharmacology identified 11 RAAS-related proteins as potential therapeutic targets for the peptides.

## Abstract

The venom of Nemopilema nomurai jellyfish represents a promising source of bioactive compounds with potential pharmacological applications. In our previous work, we identified two novel angiotensin-converting enzyme (ACE)-inhibitory peptides—IVGRPLANG (896.48 Da) and IGDEPRHQYL (1227.65 Da)—isolated from N. nomurai venom hydrolysates via papain digestion. In this study, we conducted a detailed biochemical and computational characterization of these peptides. The IC50 values were determined to be 23.81 µM for IVGRPLANG and 5.68 µM for IGDEPRHQYL. Kinetic analysis using Lineweaver–Burk plots revealed that both peptides act as competitive ACE inhibitors, with calculated inhibition constants (Ki) of 51.38 µM and 5.45 µM, respectively. To assess the structural stability of the ACE–peptide complexes, molecular dynamics simulations were performed. Root mean square deviation (RMSD) and root mean square fluctuation (RMSF) analyses provided insights into complex stability, while interaction fraction analysis elucidated key bond types and residue–ligand contacts involved in binding. Furthermore, a network pharmacology approach was employed to predict therapeutic targets within the renin–angiotensin–aldosterone system (RAAS). Eleven target proteins were identified: IVGRPLANG was associated with REN, ACE, CTSB, CTSS, and AGTR2; IGDEPRHQYL was linked to REN, AGT, AGTR1, AGTR2, KNG1, and BDKR2. Molecular docking analyses using HADDOCK software (version 2.4) were conducted for all targets to evaluate binding affinities, providing further insight into the peptides’ therapeutic potential.