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

IF 2.4 3区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY
Mohammad Y Alshahrani, Muath Suliman, Mohammad Ali Abdullah Almoyad, Shadma Wahab
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引用次数: 0

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.

通过用于癌症治疗的分子对接和 MD 模拟,确定 ZINC08101049 为一种潜在的 IL1β 抑制剂。
癌症是全球关注的重大健康问题,对全世界的发病率和死亡率都有重大影响。研究表明,白细胞介素-1β(IL1β)参与了癌症发生和发展的各个方面,包括血管生成、肿瘤生长和转移。因此,靶向 IL1β 活性是一种很有前景的癌症治疗方法。在这项研究中,我们利用分子对接和 MD 模拟发现了治疗癌症的强效 IL1β 抑制剂。我们从 ZINC15 数据库中筛选出五千个针对 IL1β 靶点的化合物,并根据其结合能筛选出前十个小分子。根据结合能(-9.1 kcal/Mol)和与 IL1β 的 GLN81、GLY136、LEU134、LYS138、SER84、THR137 和 TYR24 等氨基酸残基形成七个氢键的残余相互作用,名为 "ZINC08101049 "的小分子被优先考虑。接着,对 IL1β 单独和与 ZINC08101049 的复合物进行了 MD 模拟,以确定它们在原子水平上的行为。分子对接和 MD 模拟的结果表明,ZINC08101049 是 IL1β 的潜在抑制剂,这表明 ZINC08101049 可以作为一种有前途的小分子铺平癌症治疗的道路。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Journal of Biomolecular Structure & Dynamics
Journal of Biomolecular Structure & Dynamics 生物-生化与分子生物学
CiteScore
8.90
自引率
9.10%
发文量
597
审稿时长
2 months
期刊介绍: The Journal of Biomolecular Structure and Dynamics welcomes manuscripts on biological structure, dynamics, interactions and expression. The Journal is one of the leading publications in high end computational science, atomic structural biology, bioinformatics, virtual drug design, genomics and biological networks.
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