• Investigation the interaction between NF-κB protein and Astragaloside IV using molecular docking
  • Maryam Pakarha,1,* Ali Firouzmand,2
    1. Department of Biology, Faculty of Science, Bu-Ali Sina University, Hamedan, Iran
    2. Department of Biology, Faculty of Science, Bu-Ali Sina University, Hamedan, Iran


  • Introduction: The nuclear factor kappa B (NF-κB) signaling pathway is a master regulator of crucial cellular processes, including inflammation, immune responses, cell proliferation, and apoptosis. Its dysregulation is implicated in the pathogenesis of numerous diseases, such as chronic inflammatory disorders, autoimmune diseases, and various cancers. Consequently, NF-κB represents a highly attractive therapeutic target. Astragaloside IV (AS-IV) is a cycloartane-type triterpenoid saponin (molecular formula: C₄₁H₆₈O₁₄; MW: 785 Da), primarily isolated from Astragalus species, including the pharmacologically significant Astragalus qazvinensis. Structurally, it features a signature cyclopropane ring and multiple glycosidic moieties (notably xylose and glucose), contributing to its amphiphilic properties and receptor-binding versatility. Therefore, this study employs computational molecular docking simulations to investigate the potential binding mode, affinity, and specific interactions between Astragaloside IV (ligand) and the IκBα/NF-κB complex (receptor, PDB: 1NFI). This approach aims to provide mechanistic insights into how AS-IV might directly interfere with the IκBα/NF-κB interaction, thereby inhibiting NF-κB activation and contributing to its observed therapeutic effects.
  • Methods: In this study, at first uniport website and RCSB website was used to extract protein's 3D structure as pdb file. After this, protein was made ready for the project by making changes using Chimera software. IκBα/NF-κB complex (receptor, PDB: 1NFI) has six chains. Chain a and chain c were kept Because NF-KAPPA-B P65 was selected to investigate. Also, using chimera software, water molecules were removed from the protein and hydrogen molecules were added to its structure. After this changes, pubchem website was used to extract 2D Structure of compound as sdf file. The Ligand’s 3d structure isn’t available, so it’s created using chem3d. At the end, everything was ready for the molecular docking process using PyRx software. Also, Discovery Studio was used to analyses the results of docking. In this research, the blind docking method was used. Therefore, the defined grid box includes the entire chains of protein.
  • Results: according to numbers, there are 9 various conformation which ligand is docked to protein. in best model, binding affinity is -7.8. in weakest conformation this number is -7.3 so it is acceptable too. however, primary analyzing was done on the first model due to its suitable results.
  • Conclusion: According to docking studies, the compound has suitable interaction with NF-κB protein. Because it has suitable binding affinity (x<-5) and also in at least one of the conformations, it has RMSD lower bond and RMSD upper bond close to each other or equal. Therefore, it is concluded that this compound has the potential to become an inhibitor for the protein. However, this conclusion is based on in-silico studies. In the next stages and to prove this conclusion, in-vitro and in-vivo research should be done.
  • Keywords: NF-κB, Astragaloside IV, molecular docking, Astragalus qazvinensis,, drug design