反向对接的选择性与非选择性抑制剂找靶评价:Glide个案研究

Evaluating reverse docking on general and selective inhibitors: a case study about glide

反向对接作为一种靶标预测的有效工具,有许多方面仍待探究。对反向对接软件的客观评价可以帮助我们更好地了解这些工具的长处与短处,并在靶标预测的过程中起到指导作用。本研究中,我们评估了Glide(SP)针对选择性抑制剂与非选择性抑制剂的靶标预测能力。结果说明针对不同配体,对接打分的倾向可能存在差异,因此总体打分抽样对帮助我们更好地理解某对配体受体间的对接打分具有重要的意义。另外,对接时结合口袋的输入构象对对接结果存在一定的影响。Glide(SP)显示出较好的对非选择性抑制剂的靶标预测能力。然而,其对于选择性抑制剂的靶标预测准确度相对较低,说明该软件不适用于这方面的工作。针对COVID-19的案例研究表面凝血因子Xa可能是氯喹的潜在靶点。因此,我们认为对反向对接软件的进一步开发与靶点间打分差异的修正十分必要。

As a powerful tool for target prediction,reverse docking remains largely unexplored.The objective evaluation of reverse docking software can help us know better about the strength and weakness of these tools,hence guiding us in target prediction.In the present study,we evaluated the target prediction power of Glide(SP)against general inhibitors and selective inhibitors.The results showed that the scoring tendency could be different for each ligand,and overall scoring sampling was necessary for a better understanding of the docking score for a certain protein-ligand pair.Besides,the input conformation of the binding pocket could affect the docking result.Glide(SP)showed a preferable performance on the target prediction of the general inhibitors.However,the accuracy of the target prediction of the selective inhibitors was relatively low,indicating that Glide(SP)might not be capable for this task.The case study about COVID-19 proved that coagulation factor Xa might be a potential target of chloroquine.Therefore,we recommend the further development of reverse docking tools and rectification of inter-target scoring bias.