Molecular Docking Studies Reveal Rhein from rhubarb (Rheum rhabarbarum) as a Putative Inhibitor of ATP-binding Cassette Super-family G member 2
Molecular Docking Studies Reveal Rhein from rhubarb (Rheum rhabarbarum) as a Putative Inhibitor of ATP-binding Cassette Super-family G member 2
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DOI：
10.2174/1573406416666191219143232
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发表时间：
2021-01-01
影响因子：
2.3
通讯作者：
Kamal, Mohammad Amjad
中科院分区：
文献类型：
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作者：
Khan, Muhammad Saad;Mehmood, Bareera;Kamal, Mohammad Amjad
背景资料：ATP结合盒超家族G成员2蛋白是一种具有活性的ATP结合盒转运蛋白，具有对抗肿瘤干细胞的潜力。目的：由于缺乏潜在的ATP结合盒超家族G成员2抑制剂，我们筛选天然抑制剂，通过阻断ATP结合盒超家族G成员2蛋白的调节，可能成为控制多药耐药的安全来源。从蛋白质数据库下载ATP结合盒超家族G成员2蛋白的三维结构，并从PubChem检索训练数据集的166种选定化合物的化学结构。进行药物相似性和对接分析以筛选用于药效团生成的数据集。利用LigandScout 4.1.5对ZINC数据库的Zbc文库进行基于药效团的筛选，并利用Autodock维纳对靶蛋白的预测活性口袋进行分子对接，以评估蛋白和配体的潜在结合。结果：通过药效团筛选，确定ZINC 4098704（Rhein）为先导化合物，其与目的蛋白的结合能最小（-8.5），结合亲和力最高，具有最佳的理化性质。这种化合物是强烈建议的实验室测试，以确认其作为ATP结合盒超家族G成员2 inhibitors.Conclusion的活性：我们的计算机为基础的研究系统地选择天然先导化合物，这可能是有效的抑制ATP结合盒超家族G成员2，并可能有助于扭转多药耐药的影响，以增加化疗在癌症治疗中的有效性。
Background: ATP-binding cassette Super-family G member 2 protein is an active ATP-binding cassette transporter with the potential to combat cancer stem cells.Objective: Due to the lack of potential ATP-binding cassette Super-family G member 2 inhibitors, we screened natural inhibitors, which could be a safe source to control multidrug resistance by blocking the regulation of ATP-binding cassette Super-family G member 2 protein.Methods: Three-dimensional structure of ATP-binding cassette Super-family G member 2 protein downloaded from the protein databank and chemical structures of 166 selected compounds of the training dataset were retrieved from PubChem. Drug-likeness and docking analysis was conducted to shortlist the dataset for pharmacophore generation. LigandScout 4.1.5 used for pharmacophore-based screening of Zbc library of ZINC database and Autodock Vina were utilized for molecular docking against the predicted active pocket of the target protein to evaluate the potential association of protein and ligands. The physiochemical properties of novel compounds were calculated by admetSAR respectively.Results: Through pharmacophore-based screening, ZINC4098704 (Rhein) was identified as a lead compound which demonstrates the least binding energy (-8.5) and the highest binding affinity with the target protein and showed optimal physiochemical profile. This compound is highly recommended for a laboratory test to confirm its activity as an ATP-binding cassette Super-family G member 2 inhibitors.Conclusion: Our computer-based study systematically selected natural lead compounds, which could be effective in inhibiting ATP-binding cassette Super-family G member 2 and may help reverse the effect of multidrug resistance to increase the effectiveness of chemotherapy in cancer treatment.