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Effect of nelfinavir stereoisomers on coronavirus main protease: Molecular docking, molecular dynamics simulation and MM/GBSA study
Journal of Molecular Graphics and Modelling ( IF 2.9 ) Pub Date : 2020-12-04 , DOI: 10.1016/j.jmgm.2020.107803
Mohsen Sargolzaei

In this study, the binding strength of 32 diastereomers of nelfinavir, a proposed drug for the treatment of COVID-19, was considered against main protease. Molecular docking was used to determine the most potent diastereomers. The top three diastereomers along with apo form of protein were then considered via molecular dynamics simulation and MM-GBSA method. During the simulation, the structural consideration of four proteins considered was carried out using RMSD, RMSF, Rg and hydrogen bond analysis tools. Our data demonstrated that the effect of nelfinavir RSRSR stereoisomer on protein stability and compactness is higher than the other. We also found from the hydrogen bond analysis that this important diastereomer form three hydrogen bonds with the residues of Glu166, Gly143 and Hie41. MM/GBSA analysis showed that the binding strength of RSRSR is more than other stereoisomers and that the main contributions to binding energy are vdW and electronic terms. The nelfinavir RSRSR stereoisomer introduced in this study may be effective in the treatment of COVID-19.



中文翻译:

奈非那韦立体异构体对冠状病毒主要蛋白酶的影响:分子对接,分子动力学模拟和MM / GBSA研究

在这项研究中,考虑将32种非那非那非(一种用于治疗COVID-19的拟议药物)对主要蛋白酶的结合强度。分子对接用于确定最有效的非对映异构体。然后通过分子动力学模拟和MM-GBSA方法考虑前三个非对映异构体以及apo形式的蛋白质。在模拟过程中,使用RMSD,RMSF,Rg和氢键分析工具对四种蛋白质的结构进行了研究。我们的数据表明,奈非那韦RSRSR立体异构体对蛋白质稳定性和紧密性的影响高于其他方法。从氢键分析中我们还发现,这种重要的非对映异构体与Glu166,Gly143和Hie41的残基形成三个氢键。MM / GBSA分析表明,RSSRR的结合强度高于其他立体异构体,并且对结合能的主要贡献是vdW和电子项。这项研究中引入的奈非那韦RSRSR立体异构体可能有效治疗COVID-19。

更新日期:2020-12-14
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