Virtual screening of potential hepatocellular carcinoma inhibitors targeting J-PKAc chimera

Abstract

Background: Hepatocellular carcinoma (HCC) presents a formidable challenge in oncology, demanding innovative therapeutic avenues. This study aimed to virtual screen the potential inhibitors targeting the J-PKAc chimera, a fusion protein involving DnaJ homolog subfamily B member 1 and cAMP-dependent protein kinase catalytic subunit alpha.

Methods: The assessment employed PyRx gridbox as an intuitive interface to facilitate molecular docking simulations. Figures 1 and 2 depicted the inhibition constant and binding energy, respectively, providing quantitative insights into the interaction between ligand inhibitors and J-PKAc chimera. Seventeen compounds were scrutinized, with fascaplysine exhibiting the highest affinity for binding to the J-PKAc chimera. The original ligand, trans-tetrahydrofuran-3,4-diol(2S)-2-amino-3-phosphonooxy-propanoic acid (SEP), extracted from the protein-ligand complex structure, was used for docking validation.

Results: Among the twenty-one compounds evaluated, fascaplysine demonstrated the most significant affinity for binding to the DnaJ homolog subfamily B member 1, cAMP-dependent protein kinase catalytic subunit alpha.

Conclusion: Fascaplysine emerged as a lead candidate, demonstrating high affinity for the J-PKAc chimera. The molecular docking simulations and visualizations elucidate intricate interactions, enhancing our understanding of potential therapeutic interventions. The study not only identifies fascaplysine as a strong candidate but also contributes valuable molecular insights, paving the way for targeted and effective therapies against HCC.