Investigation of The Interaction Between Cobra Venom Cytotoxin With TNFR1 Using Computational & Experimental Approaches

Cytotoxin is a three-finger toxin present predominantly only in cobra venom. The functional site of the toxin is located at its three hydrophobic loop tips. The actual mechanism of action of cytotoxicity remains inconclusive. The present work aims to investigate the interaction between cytotoxin with death receptor families such as Fas-ligand and TNF receptors via in-silico molecular docking. A conserved cytotoxin sequence was constructed by multiple sequence alignment. The 3D structure of the universal cytotoxin was later determined using homology modelling. The proximity of toxin interaction with death receptors was visualised using HADDOCK with the calculation of intermolecular forces. TNFR1 was the best receptor interacting with cytotoxin. The possible intermolecular interactions between cytotoxin and TNFR1 were Van der Waals forces and hydrogen bonding. Our findings suggest a possibility of cytotoxin triggers caspase-mediated apoptosis through non-covalent interactions with TNFR1.