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首页> 外文期刊>Drug Target Insights >Modification of -Adenosyl--Homocysteine as Inhibitor of Nonstructural Protein 5 Methyltransferase Dengue Virus Through Molecular Docking and Molecular Dynamics Simulation
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Modification of -Adenosyl--Homocysteine as Inhibitor of Nonstructural Protein 5 Methyltransferase Dengue Virus Through Molecular Docking and Molecular Dynamics Simulation

机译：通过分子对接和分子动力学模拟修饰腺苷-同型半胱氨酸作为非结构蛋白5甲基转移酶登革热病毒抑制剂

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摘要

Dengue fever is still a major threat worldwide, approximately threatening two-fifths of the world’s population in tropical and subtropical countries. Nonstructural protein 5 (NS5) methyltransferase enzyme plays a vital role in the process of messenger RNA capping of dengue by transferring methyl groups from S-adenosyl-l-methionine to N7 atom of the guanine bases of RNA and the RNA ribose group of 2′OH, resulting in S-adenosyl-l-homocysteine (SAH). The modification of SAH compound was screened using molecular docking and molecular dynamics simulation, along with computational ADME-Tox (absorption, distribution, metabolism, excretion, and toxicity) test. The 2 simulations were performed using Molecular Operating Environment (MOE) 2008.10 software, whereas the ADME-Tox test was performed using various software. The modification of SAH compound was done using several functional groups that possess different polarities and properties, resulting in 3460 ligands to be docked. After conducting docking simulation, we earned 3 best ligands (SAH-M331, SAH-M2696, and SAH-M1356) based on ΔGbinding and molecular interactions, which show better results than the standard ligands. Moreover, the results of molecular dynamics simulation show that the best ligands are still able to maintain the active site residue interaction with the binding site until the end of the simulation. After a series of molecular docking and molecular dynamics simulation were performed, we concluded that SAH-M1356 ligand is the most potential SAH-based compound to inhibit NS5 methyltransferase enzyme for treating dengue fever.
机译：登革热仍然是世界范围内的主要威胁，大约威胁着热带和亚热带国家人口的五分之二。非结构蛋白5（NS5）甲基转移酶通过将甲基从S-腺苷-1-甲硫氨酸转移到RNA鸟嘌呤碱基的N7原子和2'的RNA核糖基团上，在登革热的信使RNA封盖过程中起着至关重要的作用。 OH，产生S-腺苷-1-高半胱氨酸（SAH）。使用分子对接和分子动力学模拟以及计算的ADME-Tox（吸收，分布，代谢，排泄和毒性）测试筛选SAH化合物的改性。使用Molecular Operating Environment（MOE）2008.10软件进行了2次模拟，而使用各种软件进行了ADME-Tox测试。使用具有不同极性和性质的几个官能团对SAH化合物进行了修饰，从而使3460个配体对接。进行对接模拟后，基于ΔG结合和分子相互作用，我们获得了3种最佳配体（SAH-M331，SAH-M2696和SAH-M1356），其结果优于标准配体。而且，分子动力学模拟的结果表明，最好的配体仍然能够保持活性位点残基与结合位点的相互作用，直到模拟结束。经过一系列的分子对接和分子动力学模拟，我们得出结论，SAH-M1356配体是最有可能抑制SA5的NS5甲基转移酶的SAH基化合物，用于治疗登革热。

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