Bioactive conformation analysis of cyclic imides as protoporphyrinogen oxidase inhibitor by combining DFT calculations, QSAR and molecular dynamic simulations.
Bioactive conformation analysis of cyclic imides as protoporphyrinogen oxidase inhibitor by combining DFT calculations, QSAR and molecular dynamic simulations.
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DOI：
10.1016/j.bmc.2009.06.003
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发表时间：
2009-07
影响因子：
3.5
通讯作者：
Li Zhang;Ge-Fei Hao;Yin Tan;Z. Xi;Mingdong Huang;Guangfu Yang
中科院分区：
文献类型：
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作者：
Li Zhang;Ge-Fei Hao;Yin Tan;Z. Xi;Mingdong Huang;Guangfu Yang
药物的活性构象是研究配体-受体相互作用的关键之一。本研究将基于密度泛函理论的构象分析与定量构效关系分析相结合，成功地建立了一种新的方法（DFT/QSAR），对25个环酰亚胺类原卟啉原氧化酶（PPO）抑制剂进行了生物活性构象分析。进一步的势能面扫描、分子对接和分子动力学模拟计算验证了DFT/QSAR衍生的构象确实与“真实的”生物活性构象非常相似。我们相信DFT/QSAR方法为小分子的生物活性构象提供了一种简单的替代方法，特别是在蛋白质三维结构未知的情况下。
Bioactive conformation of drugs is one of the key points for understanding the ligand–receptor interactions. In the present study, by combining density functional theory-based (DFT-based) conformation analysis with quantitative structure–activity relationship analysis (QSAR), we developed successfully a new approach (DFT/QSAR) to carry out bioactive conformation analyses for a series of 25 cyclic imide derivatives as protoporphyrinogen oxidase (PPO) inhibitors. Further potential energy surface scan, molecular docking and molecular dynamic simulation calculations validated that the DFT/QSAR-derived conformation is indeed very similar to the ‘real’ bioactive conformation. We believe the DFT/QSAR approach provides a simple alternative for the bioactive conformation of small molecules, especially in the case that the three-dimensional structure of protein is unknown.