Investigating the interactions of cobra venom cytotoxin-II with death domain of the adaptor protein TRADD (TNF receptor-associated death domain protein) using molecular docking models

Introduction: Significant apoptotic effects of cobra venom cytotoxin-II against various cancer cell lines have been reported in some recent studies. Cytotoxin-II induces its apoptotic effects via extrinsic pathways and activation of caspases cascade but it is not clear that interactions of this toxin with which membrane receptor (CD95/Fas, TNF-α/TNFR1, Apo2L/DR4 and Apo2L/DR5) leads to these effects. Computational simulations models are one of the best methods for investigating of the interactions between polypeptide and proteins as ligand and receptor.Methods: In the present study interactions of cytotoxin-II with death domain of the adaptor protein (TRADD) were investigated by molecular docking using ClusPro protein docking server and studied using PyMol software. The protein docking algorithms in this server select the best electrostatic and desolvation free energies interactions.Results: The method reproduced the binding of cytotoxin-II to TNF receptor-associated death domain protein and showed that most of the structures of cytotoxin-II are compatible with this receptor binding. ClusPro server also provided the best 10 fitting interactions with the lowest energy. It was shown that a number of amino acid residues have participated in the complex formation throughout this first ten conformations.Conclusion: Last experimental findings about apoptotic potential of cytotoxin-II against cancer cells confirmed by an In silico techniques that proved fitting interactions between this toxins and TNF receptor-associated death domain. Interaction of this toxin with other death receptors could be investigated by similar method. By comparison of the matching energy of these interactions, the most appropriate receptor will be identifiable.