H. Hajji, F. En-nahli, I. Aanouz, H. Zaki, T. Lakhlifi, M. A. Ajana, M. Bouachrine
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引用次数: 4
摘要
本文的目的是讨论计算机辅助药物设计中使用的各种方法和计算方法。因此,嘧啶和氮杂吲哚衍生物已被用于研究CaMKKII的抑制活性。它是一种进入大脑的酶,通过调节胃合成并作用于下丘脑的Ghrelin的产生,大大减少食物。将3D-QSAR、分子对接和ADMET等不同技术的结果应用于基于嘧啶和氮杂吲哚衍生物的23个分子的一系列新型CaMKKII抑制剂的研究。CoMFA和CoMSIA模型用于训练集中的19个分子,其确定系数R-2分别为0.970和0.902的高值,Leave One Out交叉验证系数Q(2)分别为0.614和0.583的显著值。该模型的预测能力通过外部验证进行了检验,通过使用四种化合物的测试集,预测确定系数测试R-ext(2)依次为0.778和0.972。与适当参数相适应的对准方法给出了可信的模型。CoMFA和CoMSIA模型产生用于定义3D-QSAR模式的等高线图。
Catastrophic Collision Between Obesity and COVID-19 Have Evoked the Computational Chemistry for Research in Silico Design of New CaMKKII Inhibitors Against Obesity by Using 3D-QSAR, Molecular Docking, and ADMET
The purpose of the paper is to discuss the various methods and computational approaches, which are used in computer-aided drug design. For this reason, pyrimidine and azaindole derivatives have been used to study the inhibitory activity of CaMKKII. It is an enzyme that enters the brain to greatly reduce food from regulating the production of Ghrelin that is synthesized by the stomach and acts on the hypothalamus. The obtained results from different techniques such as the 3D-QSAR, molecular docking, and ADMET were applied to study series of new CaMKKII inhibitors of 23 molecules based on pyrimidine and azaindole derivatives. The CoMFA and CoMSIA models were used in 19 molecules in the training set that give high values of determination coefficient R-2 0.970 and 0.902 respectively, and significant values of Leave-One-Out cross-validation coefficient Q(2) 0.614 and 0.583 respectively. The predictive capacity of this model was examined by external validation though using a test set of four compounds with a predicted determination coefficient test R-ext(2) of 0.778 and 0.972 successively. The method of alignment adapted with the appropriate parameters gave credible models. The CoMFA and CoMSIA models produce the contour maps which were used to define a 3D-QSAR mode.
期刊介绍:
Orbital: The Electronic Journal of Chemistry is a quarterly scientific journal published by the Institute of Chemistry of the Universidade Federal de Mato Grosso do Sul, Brazil. Original contributions (in English) are welcome, which focus on all areas of Chemistry and their interfaces with Pharmacy, Biology, and Physics. Neither authors nor readers have to pay fees. The journal has an editorial team of scientists drawn from regions throughout Brazil and world, ensuring high standards for the texts published. The following categories are available for contributions: 1. Full papers 2. Reviews 3. Papers on Education 4. History of Chemistry 5. Short communications 6. Technical notes 7. Letters to the Editor The Orbital journal also publishes a number of special issues in addition to the regular ones. The central objectives of Orbital are threefold: (i) to provide the general scientific community (at regional, Brazilian, and worldwide levels) with a formal channel for the communication and dissemination of the Chemistry-related literature output by publishing original papers based on solid research and by reporting contributions which further knowledge in the field; (ii) to provide the community with open, free access to the full content of the journal, and (iii) to constitute a valuable channel for the dissemination of Chemistry-related investigations.