Network Pharmacology, Molecular Docking, Molecular Dynamics Simulation and ADMET Analysis Predict the Molecular Mechanisms of Gomisin N and Schisandrin B as Multi-Target Agents in Primary Sclerosing Cholangitis

Abstract

Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease characterized by inflammatory, fibrotic, and immune-mediated mechanisms, with limited therapeutic options. In this study, an integrative computational strategy combining network pharmacology, molecular docking, molecular dynamics simulation, MM-GBSA binding free energy estimation, and ADMET prediction was applied to explore the potential multi-target effects of Gomisin N and Schisandrin B. A total of 48 overlapping targets between PSC-related genes and compound-predicted targets were identified, suggesting a convergent target network involving key hubs such as SRC, EGFR, and HSP90AA1. Functional enrichment analysis indicated the involvement of PI3K–Akt, VEGF, and ErbB signaling pathways, which are associated with inflammation, cell survival, and fibrosis. Molecular docking suggested moderate binding affinities of both compounds toward selected hub proteins, with interactions involving functionally relevant residues. Molecular dynamics simulations over 100 ns indicated stable trajectories, limited residue fluctuations, preserved compactness, and persistent intermolecular interactions, particularly for SRC–ligand complexes. MM-GBSA analysis further supported favorable binding free energies, with Schisandrin B showing stronger energetic stability toward SRC than Gomisin N. Drug-likeness and ADMET predictions suggested acceptable physicochemical and preliminary safety profiles, although potential CYP450-related drugdrug interactions require consideration. Overall, these findings provide computational support for the potential role of Gomisin N and Schisandrin B as multi-target candidates in PSC-related therapeutic research. However, experimental validation is required to confirm their biological activity, pharmacokinetic behavior, and safety.