Computational discovery and evaluation of berbamunine as a potential therapeutic agent targeting YAP-driven...

Schwannoma, a tumour arising from Schwann cells, is frequently driven by aberrant activation of the Yes-associated protein 1 (YAP1), particularly in NF2-associated cases. This study explores the potential of Berbamunine, a bisbenzylisoquinoline alkaloid from Berberis species, as a YAP1-targeting therapeutic agent. A comprehensive computational pipeline was employed, incorporating ADME profiling, drug-likeness assessment, toxicity prediction, molecular docking, molecular dynamics (MD) simulations, and binding free energy calculations. Berbamunine demonstrated high gastrointestinal absorption, low predicted toxicity, and strong binding affinity to YAP1 (-8.4 kcal/mol), with stable interactions confirmed through 100 ns MD simulations and MM/PBSA analysis (ΔG = -29.33 kcal/mol). Systems biology analyses including PASS prediction, network pharmacology, KEGG pathway mapping, and Gene Ontology enrichment analysis suggests that Berbamunine may interact multiple oncogenic signalling pathways associated with YAP-driven Schwannoma. These findings indicate Berbamunine has potential to inhibit YAP1-driven oncogenic processes in Schwannoma. This study provides a strong computational foundation for further experimental validation and therapeutic development.