Molecular docking, MD simulation, DFT and ADME-toxicity study on analogs of zerumbone against IKK-β enzyme as anti-cancer agents

The inhibitor of kappaB kinase beta (IKK-β) is an important target for the therapeutic treatment of cancer and inflammatory diseases. On the other hand, zerumbone an isolate from Zingiber zerumbet has become an important molecule for targeting various cancer drug targets and enzyme. Although zerumbone is also a good inhibitor of IKK-β, its usage is limited because of its bioavailability problem. Hence, the objective of this investigation focuses on discovering new analogs of zerumbone with better bioavailability. The study involves DFT-based molecular docking and molecular dynamics simulation studies on zerumbone against the IKK-β enzyme. The best docking pose of the analogs was further analyzed for molecular interaction map and carried forward for molecular dynamics simulation production. They were also analyzed for HOMO and LUMO energies calculated at DFT/B3LYP/6-31G (d′, p′) levels of theory to calculate the band gap energy. The study observed that the analogs of zerumbone inhibit the IKK-β with favorable binding affinity than zerumbone.