Department of Medical Biotechnology, National Institute of Genetic Engineering and Biotechnology, Tehran, Iran.
Department of Systems Biotechnology, National Institute of Genetic Engineering and Biotechnology, Tehran, Iran.
J Biomol Struct Dyn. 2022 Sep;40(14):6228-6242. doi: 10.1080/07391102.2021.1880480. Epub 2021 Feb 3.
The SENP1 (Sentrin-Specific Protease1) is essential for desumoylation. SENP1 plays an essential role in many diseases such as cardiovascular disease, diabetes and cancer via targeting GATA2, NEMO, Pin1, SMAD4 and HIF-1α for deSUMOylation. Considering that, over expression of SENP1 was reported in cancer, thus an optional inhibitor of SENP1 can restitute the balance to the skewed system of SUMO and act as an effective therapeutic agent. The purpose of this study was to select and to sort inhibitors with a stronger binding affinity with SENP1. Molecular docking of SENP1 with natural compounds including Gallic acid, Caffeic acid, Thymoquinone, Thymol, Betaine, Alkannin, Ellagic acid, Betanin, Shikonin, Betanidin and Momordin IC was performed using AutoDock 4, then docking complexes for molecular dynamics (MD) simulation with GROMACS 4.6.5 were applied. Results with RMSD, RMSF, SASA, DSSP, gyrate, H-bond, ADMET and TOPKAT measurements, binding energy and structural features were surveyed. Among those, Gallic acid has shown the most significant results including RMSD and RMSF plots with high stability, high hydrogen bonds, high binding energy and the highest intermolecular bonds with SENP1. Gallic acid demonstrated strong connections and results of toxicity better than Momordin as control. Gallic acid is a phenolic compound which affects several pharmacological and biochemical pathways and has strong antioxidant, anti-inflammatory, antimutagenic and anticancer properties. Further research can improve the appropriate use of plant products drastically. Basic, pre-clinical and clinical research on Gallic acid may provide a roadmap for its ultimate application in the field of cancer prevention.Communicated by Ramaswamy H. Sarma.
SENP1（Sentrin-Specific Protease1）对于去 SUMO 化至关重要。SENP1 通过靶向 GATA2、NEMO、Pin1、SMAD4 和 HIF-1α 进行去 SUMO 化，在心血管疾病、糖尿病和癌症等许多疾病中发挥着重要作用。鉴于此，已有研究报道 SENP1 在癌症中过度表达，因此 SENP1 的可选抑制剂可以恢复 SUMO 失衡系统的平衡，并作为有效的治疗剂。本研究旨在选择和筛选与 SENP1 具有更强结合亲和力的抑制剂。使用 AutoDock 4 对 SENP1 与包括没食子酸、咖啡酸、姜黄素、百里酚、甜菜碱、安卡宁、鞣花酸、甜菜碱、紫草素、betanidin 和 Momordin IC 在内的天然化合物进行分子对接，然后应用 GROMACS 4.6.5 对对接复合物进行分子动力学（MD）模拟。结果采用 RMSD、RMSF、SASA、DSSP、gyrate、氢键、ADMET 和 TOPKAT 测量、结合能和结构特征进行评估。其中，没食子酸表现出最显著的结果，包括具有高度稳定性的 RMSD 和 RMSF 图、高氢键、高结合能以及与 SENP1 之间的最高分子间键。没食子酸表现出与 Momordin（作为对照）相比具有更强的连接和毒性结果。没食子酸是一种酚类化合物，它影响多种药理学和生物化学途径，具有很强的抗氧化、抗炎、抗突变和抗癌特性。进一步的研究可以大大改善植物产品的合理使用。关于没食子酸的基础、临床前和临床研究可能为其在癌症预防领域的最终应用提供路线图。由 Ramaswamy H. Sarma 交流。
