In-silico investigation of RPS6KB1 associated cancer inhibitor: a drug repurposing study.

IF 2.7 3区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY
Saravanan Rajendrasozhan, Irfan Ahmad, Safia Obaidur Rab, Mohammad Y Alshahrani, Eman Abdullah Almuqri, Jamshaid Ahmad Siddiqui, Md Mushtaque
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引用次数: 0

Abstract

The ribosomal protein S6 kinase beta-1 (RPS6KB1), also known as p70S6 kinase, plays a crucial role in various disease-related conditions such as diabetes, obesity, and cancer. Its activity is regulated by phosphorylation events, including phosphorylation of Threonine 389 in the hydrophobic motif by the mammalian target of rapamycin complex 1 (mTORC1) and phosphorylation of Threonine 229 in the activation loop by PDK1 (phosphoinositide-dependent kinase 1). However, other phenomena connected to RPS6KB1 remain unknown. In this study, we employed virtual screening and molecular docking techniques on the molecules in the ZINC library to identify potential inhibitors. Molecular dynamics (MD) simulations and MMGBSA calculations were carried out on promising compounds to determine their binding affinity and stability. We also evaluated the drug-likeness properties of the selected compounds. A comparative study between the native RPS6KB1 structure, co-crystal ligands, and the shortlisted molecules from the ZINC dataset was carried out. The identified molecules possess significant potential for future in vitro and in vivo studies, paving the way for developing effective cancer treatments.

RPS6KB1相关癌症抑制剂的分子内研究:一项药物再利用研究。
核糖体蛋白 S6 激酶 beta-1(RPS6KB1)又称 p70S6 激酶,在糖尿病、肥胖症和癌症等各种疾病中发挥着至关重要的作用。其活性受磷酸化事件调控,包括雷帕霉素哺乳动物靶标复合体 1(mTORC1)对疏水基团中苏氨酸 389 的磷酸化,以及 PDK1(磷脂依赖性激酶 1)对活化环中苏氨酸 229 的磷酸化。然而,与 RPS6KB1 相关的其他现象仍然未知。在这项研究中,我们对 ZINC 库中的分子采用了虚拟筛选和分子对接技术,以确定潜在的抑制剂。我们对有潜力的化合物进行了分子动力学(MD)模拟和 MMGBSA 计算,以确定它们的结合亲和力和稳定性。我们还评估了所选化合物的药物相似性。我们对原生 RPS6KB1 结构、共晶体配体和 ZINC 数据集中的入围分子进行了比较研究。所发现的分子在未来的体外和体内研究中具有巨大潜力,为开发有效的癌症治疗方法铺平了道路。
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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