Tumor necrosis factor- α Inhibition analysis by chemotherapy agent through QM/MM studies

Abstract

TNF (Tumor Necrosis Factor) is a multifunctional cytokine with a strong pro-inflammatory action and it is a proven therapeutic target receptor for a variety of autoimmune and inflammation-related illnesses. The current investigation is looking for a new chemotherapy small lead molecule that can directly bind to TNF receptors and modify the conformation. The TNF-α fold was docked with the 56 AI-designed molecules by a three-step algorithm in the Schrodinger Maestro interface. The interaction analysis results revealed that the best-hit molecule with a binding capacity score of -6.987 Kcal/mol and the MMGBSA value was found to be -52.42 Kcal/mol with the TNF receptor. Interaction map illustrates that 29 active amino acid of TNF receptor networked through 3 hydrogen bond, hydrophobic, 2 Salt bridges and negative charges type interactions with ring system such as piperazine and azetidine od the best hit molecule. Further, the environment solvent stability was confirmed using MD simulation in Desmund interface and analyzed the trajectory at 100 ns scale level, and it concludes that the formed bonds are 40–99% strong enough to modify the secondary structure of the TNF-α. Which leads target specific inhibition and safe chemotherapy agent for Tumor necrosis factor (TNF-α)