Faculty of Chemistry, Shahrood University of Technology, Shahrood, Iran.
J Mol Graph Model. 2021 Mar;103:107803. doi: 10.1016/j.jmgm.2020.107803. Epub 2020 Dec 4.
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.
在这项研究中，考虑了 32 种奈非那韦的非对映异构体与主蛋白酶的结合强度，奈非那韦是一种用于治疗 COVID-19 的候选药物。使用分子对接来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 方法考虑了前三名的非对映异构体以及apo 形式的蛋白质。在模拟过程中，使用 RMSD、RMSF、Rg 和氢键分析工具对所考虑的四种蛋白质的结构进行了考虑。我们的数据表明，奈非那韦 RSRSR 对映异构体对蛋白质稳定性和紧凑性的影响高于其他对映异构体。我们还从氢键分析中发现，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，RSRSR 的结合强度超过其他立体异构体，而对结合能的主要贡献是 vdW 和电子项。本研究中引入的奈非那韦 RSRSR 对映异构体可能对 COVID-19 的治疗有效。
