Computational Investigation of the Unveils NSD2 Inhibition Potential of Berberis vulgaris, Sambucus nigra, and Morus alba through Virtual Screening, Molecular Docking, MD Simulation, and DFT Analyses

Nuclear receptor binding set domain protein 2 (NSD2) plays a key role in chromatin regulation and is associated with different cancers and other developmental problems. Berries are rich in major secondary metabolites with anticancer properties. Here, we virtually screened 145 berry phytochemicals as putative NSD2 inhibitors via structure-based virtual screening, molecular docking, MD simulations, and DFT and ADMET analyses. Among them, α-carotene had the maximum docking score of -9.9 kcal/mol, followed by sulfuretin and β-amyrin. MD simulation analysis revealed that the dynamic behavior of the ligand‒NSD2 complexes was within the limit, indicating no significant changes in the structural integrity of the ligand upon interaction with the receptor. DFT studies have indicated that α-carotene is the most stable and reactive molecule, followed by sulfuretin and β-amyrin. These molecules respect the minimum criteria of Lipinski's rule with acceptable ADMET profiles. These data suggest that these phytochemicals may play a role in the inhibition of the NSD2 protein and associated cancers. The selected phytochemicals α-carotene, sulfuretin and β-amyrin are abundant in Berberis vulgaris (barberry), Sambucus nigra (elder berry), and Morus alba (white mulberry). Berberis vulgaris, Sambucus nigra, and Morus alba have shown efficient anticancer properties. Therefore, establishing these phytoconstituents via in vitro and in vivo experiments could be beneficial for humankind.