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首页> 外文期刊>Proteins: Structure, Function, and Genetics >Probing ligand binding modes of human cytochrome P450 2J2 by homology modeling, molecular dynamics simulation, and flexible molecular docking.
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Probing ligand binding modes of human cytochrome P450 2J2 by homology modeling, molecular dynamics simulation, and flexible molecular docking.

机译：通过同源性建模，分子动力学模拟和灵活的分子对接，探索人细胞色素P450 2J2的配体结合模式。

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摘要

Cytochrome P450 (P450) 2J2 catalyzes epoxidation of arachidonic acid to eicosatrienoic acids, which are related to a variety of diseases such as coronary artery disease, hypertension, and carcinogenesis. Recent experimental data also suggest that P450 2J2 could be a novel biomarker and a potential target for cancer therapy. However, the active site topology and substrate specificity of this enzyme remain unclear. In this study, a three-dimensional model of human P450 2J2 was first constructed on the basis of the crystal structure of human P450 2C9 in complex with a substrate using homology modeling method, and refined by molecular dynamics simulation. Flexible docking approaches were then employed to dock four ligands into the active site of P450 2J2 in order to probe the ligand-binding modes. By analyzing the results, active site architecture and certain key residues responsible for substrate specificity were identified on the enzyme, which might be very helpful for understanding the enzyme's biological role and providing insights for designing novel inhibitors of P450 2J2.
机译：细胞色素P450（P450）2J2催化花生四烯酸环氧化为二十碳三烯酸，二十碳三烯酸与多种疾病有关，例如冠心病，高血压和致癌作用。最近的实验数据还表明，P450 2J2可能是一种新型的生物标志物，并且可能成为癌症治疗的潜在靶标。但是，该酶的活性位点拓扑结构和底物特异性仍不清楚。在这项研究中，人类P450 2J2的三维模型首先基于人类P450 2C9的晶体结构与底物复合，采用同源建模方法构建，然后通过分子动力学模拟进行精炼。然后采用灵活的对接方法将四个配体对接到P450 2J2的活性位点中，以探测配体结合模式。通过分析结果，在酶上鉴定了活性位点结构和负责底物特异性的某些关键残基，这可能对理解酶的生物学作用以及为设计新型P450 2J2抑制剂提供有用的见识。

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