UNASSIGNED:我们对OliveNetTM文库的橄榄类环烯醚萜类化合物进行了虚拟筛选,以预测SARS-CoV-2PLpro的抑制作用。评估两个对接程序的性能的基准分子对接方案被应用于执行虚拟筛选。还进行了与PLpro对接的排名最高的橄榄Secoippoidid的分子动力学稳定性分析。
未经评估:基准虚拟筛选使用了两个免费提供的对接程序,AutoDockVina1.1.2.和AutoDock4.2.1。用于将橄榄Secoipproids分子对接到单个PLpro结构。筛选还包括来自DEKOIS2.0文库的已知活性和诱饵分子的基准结构。根据预测的结合能,对接程序对筛选的分子进行排名。我们应用了通常的性能评估指标来使用预测的等级评估对接程序。与PLpro结合的排名最高的橄榄类iscoippoidid的分子动力学,以及在Desmond动力学分析的最后50ps中使用三次迭代计算MM-GBSA能量的方法,支持了稳定性预测。
UNASSIGNED:预测性曲线表明AutoDockVina比AutoDock具有更好的预测能力,尽管活性分子排名之间存在中等相关性(Kendall的秩相关性(τ)=0.581)。有趣的是,两个相同的分子,去甲基橄榄苦苷苷配基,和Oleuroside丰富了这两个程序预测的排名前1%的橄榄Secoippoids。当通过分子动力学模拟分析50ns的稳定性时,与通过在AutoDockVina中对接获得的PLpro结合的去甲基苦苷苷苷元显示出RMSD,RMSF<2,MM-GBSA能量为-94.54±6.05kcal/mol,表明稳定性良好。分子动力学还揭示了去甲基苦苷糖苷配基与PLpro的结合位点2和3的相互作用,暗示了一种有效的抑制作用。此外,在98%的模拟时间内,去甲基苦苷苷元的两个酚羟基与PLpro的Asp302保持了两个氢键,说明这些基团在受体结合中的重要性。
UNASSIGNED:AutoDockVina准确检索了活性分子,并预测去甲基苦豆苷苷配基是PLpro的最佳抑制剂。阿拉伯饮食由富含secoipproids的橄榄产品组成,受益于PLpro抑制特性,并降低病毒感染的风险。
UNASSIGNED: We performed a virtual screening of olive secoiridoids of the OliveNetTM library to predict SARS-CoV-2 PLpro inhibition. Benchmarked molecular docking protocol that evaluated the performance of two docking programs was applied to execute virtual screening. Molecular dynamics stability analysis of the top-ranked olive secoiridoid docked to PLpro was also carried out.
UNASSIGNED: Benchmarking virtual screening used two freely available docking programs, AutoDock Vina 1.1.2. and AutoDock 4.2.1. for molecular docking of olive secoiridoids to a single PLpro structure. Screening also included benchmark structures of known active and decoy molecules from the DEKOIS 2.0 library. Based on the predicted binding energies, the docking programs ranked the screened molecules. We applied the usual performance evaluation metrices to evaluate the docking programs using the predicted ranks. Molecular dynamics of the top-ranked olive secoiridoid bound to PLpro and computation of MM-GBSA energy using three iterations during the last 50 ps of the analysis of the dynamics in Desmond supported the stability prediction.
UNASSIGNED: Predictiveness curves suggested that AutoDock Vina has a better predictive ability than AutoDock, although there was a moderate correlation between the active molecules rankings (Kendall\'s correlation of rank (τ) = 0.581). Interestingly, two same molecules, Demethyloleuropein aglycone, and Oleuroside enriched the top 1 % ranked olive secoiridoids predicted by both programs. Demethyloleuropein aglycone bound to PLpro obtained by docking in AutoDock Vina when analyzed for stability by molecular dynamics simulation for 50 ns displayed an RMSD, RMSF<2 Å, and MM-GBSA energy of -94.54 ± 6.05 kcal/mol indicating good stability. Molecular dynamics also revealed the interactions of Demethyloleuropein aglycone with binding sites 2 and 3 of PLpro, suggesting a potent inhibition. In addition, for 98 % of the simulation time, two phenolic hydroxy groups of Demethyloleuropein aglycone maintained two hydrogen bonds with Asp302 of PLpro, specifying the significance of the groups in receptor binding.
UNASSIGNED: AutoDock Vina retrieved the active molecules accurately and predicted Demethyloleuropein aglycone as the best inhibitor of PLpro. The Arabian diet consisting of olive products rich in secoiridoids benefits from the PLpro inhibition property and reduces the risk of viral infection.