Molecular docking analysis of marine bioactive compounds targeting vaca and caga virulence factors of helicobacter pylori

Abstract

Helicobacter pylori (H. pylori), a Group I carcinogen, is associated with a range of gastrointestinal and extra-gastric diseases.
This study aimed to evaluate the interaction of selected bioactive compounds, rosmarinic acid and stigmasterol, with key H. pylori virulence proteins, CagA (PDB ID: 4DVY) and VacA (PDB ID: 2QV3).
Using molecular docking analysis. The three-dimensional structures of the target proteins were retrieved from the Protein Data Bank, and docking simulations were performed using AutoDockTools 1.5.7, followed by interaction analysis in PyMOL. Rosmarinic acid demonstrated a binding energy of −5.1 kcal/mol and an inhibitory constant (Ki) of 18.35 mM against CagA, with interactions involving residues such as LEU475 and LYS613, while stigmasterol showed a binding energy of −3.39 kcal/mol and Ki of 3.25 mM, interacting with residues including ARG399 and GLU406.
In the case of VacA, stigmasterol exhibited a binding energy of −4.38 kcal/mol (Ki 6.16 mM), whereas rosmarinic acid showed −2.93 kcal/mol (Ki 7.1 mM), with interactions observed at residues such as LYS680 and TYR729. These findings indicate that both compounds are capable of interacting with key residues of CagA and VacA proteins, with variations in binding affinity; however, as molecular docking provides only predictive insights into ligand–protein interactions, further experimental validation is required to confirm their biological activity and potential therapeutic relevance.