Aim and Objective: To evaluate a set of seventy phytochemicals for their potential ability
to bind the inhibitor of nuclear factor kappaB kinase beta (IKK-β) which is a prime target for
cancer and inflammatory diseases.
Materials and Methods: Seventy phytochemicals were screened against IKK-β enzyme using
DFT-based molecular docking technique and the top docking hits were carried forward for molecular
dynamics (MD) simulation protocols. The ADME-Toxicity analysis was also carried out for
the top docking hits.
Results: Sesamin, matairesinol and resveratrol were found to be the top docking hits with a total
score of -413 kJ/mol, -398.11 kJ/mol and 266.73 kJ/mol, respectively. Glu100 and Gly102 were
found to be the most common interacting residues. The result from MD simulation observed a
stable trajectory with a binding free energy of -107.62 kJ/mol for matairesinol, -120.37 kJ/mol for
sesamin and -40.56 kJ/mol for resveratrol. The ADME-Toxicity prediction observed that these
compounds fall within the permissible area of Boiled-Egg and it does not violate any rule for
pharmacological criteria, drug-likeness etc.
Conclusion: The study interprets that dietary phytochemicals are potent inhibitors of IKK-β enzyme
with favorable binding affinity and less toxic effects. In fact, there is a gradual rise in the use
of plant-derived molecules because of its lesser side effects compared to chemotherapy. The study
has also provided an insight by which the phytochemicals inhibited the IKK-β enzyme. The
investigation would also provide in understanding the inhibitory mode of certain dietary
phytochemicals in treating cancer.