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首页> 外文期刊>Journal of molecular graphics & modelling >In silico modeling of the type 2 IDI enzymes of Bacillus licheniformis, Pseudomonas stutzeri, Streptococcus pyogenes, and Staphylococcus aureus for virtual screening of potential inhibitors of this therapeutic target
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In silico modeling of the type 2 IDI enzymes of Bacillus licheniformis, Pseudomonas stutzeri, Streptococcus pyogenes, and Staphylococcus aureus for virtual screening of potential inhibitors of this therapeutic target

机译：对地衣芽孢杆菌，斯氏假单胞菌，化脓性链球菌和金黄色葡萄球菌的2型IDI酶进行计算机模拟，以虚拟筛选该治疗靶点的潜在抑制剂

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摘要

Isopentenyl diphosphate isomerase is an essential enzyme in those living organisms such as pathogenic strains of Streptococcus and Staphylococcus genera which rely on the Mevalonate pathway for the production of isoprenoids. The pathogens contain type 2 IDI in contrast to human that contains type 1 IDI. Therefore, the type 2 IDI may be a potential target for the therapy of some infectious diseases. In the current study, a virtual screening by docking was performed among 2000 chemicals from CoCoCo library to find a specific inhibitor for type 2 IDIs. To this end, the structures of the type 2 IDIs of Bacillus licheniformis, Pseudomonas stutzeri, Streptococcus pyogenes, and Staphylococcus aureus were molded using comparative modeling and Hidden Markov Model (HMM) based prediction. The predicted models were evaluated based on Q-mean and Prosa score. Molegro Virtual Docker with MolDock scoring function was used for measuring the binding affinity of the found inhibitor to the active site of the models. Also the inhibition effect of the compound was virtually tested on the crystallography-solved structures of the Sulfolobus shibatae and Thermus thermophilus type 2 IDIs as well as the Escherichia coli type 1 IDI. Finally, the inhibition effect of the found inhibitor was virtually tested on the human type 1 IDI. Interestingly, the results suggest that the inhibitor efficiently binds to and inhibits the bacterial IDIs especially the type 2 IDIs of pathogens while it is not inhibiting the human IDI.
机译：异戊烯基二磷酸异构酶是那些依赖甲羟戊酸途径生产类异戊二烯的活生物体（如链球菌和葡萄球菌属的致病菌株）中的必需酶。与包含1型IDI的人相比，病原体包含2型IDI。因此，2型IDI可能是治疗某些传染病的潜在目标。在当前的研究中，对来自CoCoCo库的2000种化学药品进行了对接虚拟筛选，以发现2型IDI的特异性抑制剂。为此，使用比较建模和基于隐马尔可夫模型（HMM）的预测，对地衣芽孢杆菌，斯氏假单胞菌，化脓性链球菌和金黄色葡萄球菌的2型IDI结构进行了建模。基于Q均值和Prosa得分评估了预测模型。具有MolDock评分功能的Molegro Virtual Docker用于测量发现的抑制剂与模型活性位点的结合亲和力。还实际上测试了该化合物对Shibatae的Sulfolobus shibatae和Thermus thermophilus 2型IDI以及大肠杆菌1 IDI的晶体学解析结构的抑制作用。最后，实际上测试了发现的抑制剂对人1型IDI的抑制作用。有趣的是，该结果表明该抑制剂有效结合并抑制细菌IDI，尤其是病原体的2型IDI，同时不抑制人IDI。

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