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

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.

癌症是全球范围内不容忽视的重大公共卫生问题，对全球发病率与死亡率均具有显著影响。已有研究表明，白细胞介素-1β（Interleukin-1 beta, IL1β）参与了癌症发生发展的多个关键环节，包括血管生成、肿瘤增殖与转移。因此，靶向IL1β活性有望成为癌症治疗的极具潜力的策略。本研究采用分子对接与分子动力学（MD）模拟技术，旨在筛选可用于癌症治疗的强效IL1β抑制剂。研究从ZINC15数据库中选取5000种化合物，针对IL1β靶点进行虚拟筛选，并依据结合能评分筛选出排名前十的小分子化合物。其中，名为ZINC08101049的小分子凭借其-9.1 kcal/mol的结合能与特异性残基相互作用脱颖而出：该小分子可与IL1β的GLN81、GLY136、LEU134、LYS138、SER84、THR137及TYR24共7个氨基酸残基形成氢键相互作用。随后，本研究对游离IL1β及其与ZINC08101049形成的复合物开展MD模拟，以解析二者在原子层面的动态行为特征。分子对接与MD模拟的结果表明，ZINC08101049是一种潜在的IL1β抑制剂，提示该小分子有望成为极具应用前景的癌症治疗候选药物。