阐明斜叶变种（西兰花）中的植物化合物对甲状腺功能亢进的作用：一种计算机模拟方法。
Elucidating the role of phytocompounds from var. italic (Broccoli) on hyperthyroidism: an in-silico approach.
作者信息
Daniel Derina J Pearlin, Shanmugasundaram Shruthi, Chandra Mohan Karunya Sri, Siva Bharathi Velayutham, Abraham Jins K, Anbazhagan Parthiban, Pavadai Parasuraman, Ram Kumar Pandian Sureshbabu, Sundar Krishnan, Kunjiappan Selvaraj
机构信息
Department of Biotechnology, Kalasalingam Academy of Research and Education, Krishnankoil, 626126 Tamil Nadu India.
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, M.S. Ramaiah University of Applied Sciences, M S R Nagar, Bengaluru, 560054 Karnataka India.
出版信息
In Silico Pharmacol. 2024 Jan 4;12(1):6. doi: 10.1007/s40203-023-00180-2. eCollection 2024.
UNLABELLED
Thyroid hormone (TH) plays a crucial role in regulating the metabolism in every cell and all organs in of the human body. TH also control the rate of calorie burning, body weight, and function of the heartbeat. Therefore, the aim of the present study is to investigate the role of phytocompounds from var. italic (Broccoli) against irregularities of TH biosynthesis (hyperthyroidism) through in silico molecular modelling. Initially, the genetic network was built with graph theoretical network analysis to find the right target to control excessive TH production. Based on the network analysis, the three-dimensional crystal structure of the mammalian enzyme lactoperoxidase (PDB id: 5ff1) was retrieved from the protein data bank (PDB), and the active site was predicted using BIOVIA Discovery studio. Sixty-three phytocompounds were selected from the IMPPAT database and other literature. Selected sixty-six phytocompounds were docked against lactoperoxidase enzyme and compared with the standard drug methimazole. Based on the docking scores and binding energies, the top three compounds, namely brassicoside (- 10.00 kcal × mol), 24-methylene-25-methylcholesterol (- 9.50 kcal × mol), 5-dehydroavenasterol (- 9.40 kcal × mol) along with standard drug methimazole (- 4.10 kcal × mol) were selected for further ADMET and molecular dynamics simulation analysis. The top-scored compounds were for their properties such as ADMET, physicochemical and drug-likeness. The molecular dynamics simulation analyses proved the stability of lactoperoxidase-ligand complexes. The intermolecular interaction assessed by the dynamic conditions paved the way to discover the bioactive compounds brassicoside, 24-methylene-25-methylcholesterol, and 5-dehydroavenasterol prevent the excessive production of thyroid hormones.
SUPPLEMENTARY INFORMATION
The online version contains supplementary material available at 10.1007/s40203-023-00180-2.
未标注
甲状腺激素（TH）在调节人体每个细胞和所有器官的新陈代谢中起着至关重要的作用。TH还控制着卡路里燃烧速率、体重和心跳功能。因此，本研究的目的是通过计算机分子建模研究来自意大利变种（西兰花）的植物化合物对TH生物合成异常（甲状腺功能亢进）的作用。最初，通过图论网络分析构建遗传网络，以找到控制过量TH产生的合适靶点。基于网络分析，从蛋白质数据库（PDB）中检索哺乳动物酶乳过氧化物酶的三维晶体结构（PDB编号：5ff1），并使用BIOVIA Discovery studio预测其活性位点。从IMPPAT数据库和其他文献中选择了63种植物化合物。将选定的66种植物化合物与乳过氧化物酶进行对接，并与标准药物甲巯咪唑进行比较。根据对接分数和结合能，选择排名前三的化合物，即芸苔糖苷（-10.00千卡×摩尔）、24-亚甲基-25-甲基胆固醇（-9.50千卡×摩尔）、5-脱氢燕麦甾醇（-9.40千卡×摩尔）以及标准药物甲巯咪唑（-4.10千卡×摩尔）进行进一步的ADMET和分子动力学模拟分析。得分最高的化合物具有ADMET、物理化学和类药物等性质。分子动力学模拟分析证明了乳过氧化物酶-配体复合物的稳定性。通过动态条件评估的分子间相互作用为发现生物活性化合物芸苔糖苷、24-亚甲基-25-甲基胆固醇和5-脱氢燕麦甾醇防止甲状腺激素过量产生铺平了道路。
补充信息
在线版本包含可在10.1007/s40203-023-00180-2获取的补充材料。
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