Identification of ZINC08101049 as a potential IL1β inhibitor through molecular docking and MD simulations for cancer therapeutics

Abstract

Cancer is a significant global health concern that has a major impact on morbidity and mortality worldwide. Research has demonstrated the involvement of Interleukin-1 beta (IL1β) in various aspects of cancer development and progression, including angiogenesis, tumor growth and metastasis. Consequently, targeting IL1β activity represents a promising approach for cancer therapeutics. In this study, we utilized molecular docking and MD simulations to discover potent IL1β inhibitors for the treatment of cancer. Five thousand compounds from ZINC15 database were screened against IL1β target, and the top ten small molecules were selected based on their binding energy. The small molecule named ‘ZINC08101049’ was prioritized based on binding energy (−9.1 kcal/Mol) and residual interaction specifically forming seven hydrogen bonds with amino acid residues namely GLN81, GLY136, LEU134, LYS138, SER84, THR137 and TYR24 of IL1β. Next, IL1β alone and in complex with ZINC08101049 was subjected to MD simulations to determine their behavior at atomic level. The results of molecular docking and MD simulation revealed ZINC08101049 as a potential inhibitor of IL1β, reflecting that ZINC08101049 can emerge as a promising small molecule paving for cancer therapeutics. Communicated by Ramaswamy H. Sarma